Safety, Tolerability and Pharmacodynamic Effect of Fazirsiran (TAK-999, ARO-AAT)

A Placebo-Controlled, Multi-dose, Phase 2 Study to Determine the Safety, Tolerability and Pharmacodynamic Effect of Fazirsiran (TAK-999, ARO-AAT) in Patients With Alpha-1 Antitrypsin Deficiency (AATD) [SEQUOIA]

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03945292

Acronym

SEQUOIA

Enrollment

Registered

2019-05-10

Start date

2019-08-07

Completion date

2023-09-18

Last updated

2025-11-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Alpha 1-Antitrypsin Deficiency

Brief summary

The purpose of AROAAT2001 (SEQUOIA) is to evaluate the safety, efficacy and tolerability of multiple doses of the investigational product, Fazirsiran Injection, administered subcutaneously to participants with alpha-1 antitrypsin deficiency (AATD).

Detailed description

Participants will be enrolled to receive multiple subcutaneous injections of Fazirsiran Injection (also referred to as TAK-999 Injection or ARO-AAT Injection) or placebo. Eligible participants will require a pre-dose biopsy completed as part of the study within the screening window. However, any participant with a biopsy result within 1 year of screening showing no fibrosis does not require a pre-dose biopsy. Only participants who have liver fibrosis will undergo a post-dose biopsy and may continue treatment in an open-label phase.

Interventions

DRUGFazisiran Injection

solution for subcutaneous (sc) injection

OTHERPlacebo

sterile normal saline (0.9% NaCl), calculated to match active comparator, for sc injection

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Diagnosis of AATD * Liver biopsy at Screening indicating liver fibrosis (score less than F4); a patient with no fibrosis may participate based on a previous biopsy conducted within one year * Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception * Willing to provide written informed consent and to comply with study requirements * Non-smoker for at least 1 year * No abnormal finding of clinical relevance at Screening

Exclusion criteria

* Clinically significant health concerns other than AATD * Previous diagnosis or diagnosis at Screening of definitive liver cirrhosis * Previous lung or liver transplant due to AATD * Regular use of alcohol within one month prior to Screening * Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study involving therapeutic intervention * Use of illicit drugs within 1 year prior to Screening NOTE: additional inclusion/

Design outcomes

Primary

Measure	Time frame
Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16	Baseline, Week 16 (+/- 2 weeks)

Secondary

Measure	Time frame	Description
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	From dose administration of the first dose of open-label phase fazirsiran through EOS or Early Termination (up to Week 196).	An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with this treatment. A serious adverse event (SAE) is an AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction. TEAEs/TESAEs are defined as those AEs that first occurred or worsened in severity following dose administration through end of study (EOS) or Early Termination or first dose of open-label phase fazirsiran.
Absolute Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis	Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks)	Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96.
Percent Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis	Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks)	Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96.
Absolute Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis	Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks)	Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96.
Percent Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis	Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks)	Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96.
Absolute Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis	Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks)	Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96.
Percent Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis	Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks)	Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96.
Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)	PDLB=post-dose liver biopsy
Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)	PDLB=post-dose liver biopsy
Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)	PDLB=post-dose liver biopsy
Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)	PDLB=post-dose liver biopsy
Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)	PDLB=post-dose liver biopsy
Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)	PDLB=post-dose liver biopsy
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	Double Blind Phase (up to Week 48): dose administration through end of study (EOS) or Early Termination or first dose of open-label phase fazirsiran.	An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with this treatment. A serious adverse event (SAE) is an AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction. TEAEs/TESAEs are defined as those AEs that first occurred or worsened in severity following dose administration through end of study (EOS) or Early Termination or first dose of open-label phase fazirsiran.
Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)	PDLB=post-dose liver biopsy
Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124,136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)	PDLB=post-dose liver biopsy
Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)	PDLB=post-dose liver biopsy
Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)	PDLB=post-dose liver biopsy
Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)	PDLB=post-dose liver biopsy
Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)	PDLB=post-dose liver biopsy
Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)	PDLB=post-dose liver biopsy
Absolute Change in Serum Z-AAT Over Time Through EOS	Baseline, Weeks 2, 4, 6, 16, 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)	PDLB=post-dose liver biopsy
Percent Change in Serum Z-AAT Over Time Through EOS	Baseline, Weeks 2, 4, 6, 16, 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)	PDLB=post-dose liver biopsy
Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Fazirsiran participants without fibrosis: Pre-dose, 1 hour, 2 hour, 24 hours post-dose on Day 1 (+/- 1 day). Fazirsiran participants with fibrosis: Pre-dose, 1 hour, 2 hours, 24 hours post-dose on Day 1 and Week 16 (+/- 1 day).	—
Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Baseline, Weeks 4, 16, 28, 40, 48, 52, 64, 76, 88, 96, 100, 112, 124, 136, 148 or Early Termination (up to 148 weeks)	PDLB=post-dose liver biopsy
Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis	Baseline, Post-dose at Weeks 48 (+/- 2 weeks) or Week 72 (+/- 4 weeks) or Week 96 (+/- 4 weeks)	The METAVIR scoring system is a system used to assess the extent of inflammation and fibrosis by histopathological evaluation in a liver biopsy. The stage represents the amount of fibrosis or scarring: 0= no fibrosis; 1=portal fibrosis without septa; 2=portal fibrosis with few septa; 3=numerous septa without cirrhosis; 4=cirrhosis. A higher score indicates a worse condition.
Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124,136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)	PDLB=post-dose liver biopsy

Countries

Germany, Italy, Netherlands, Portugal, Spain, United States

Participant flow

Pre-assignment details

Randomization was performed within each dose cohort to maintain blinding due to different dose volumes in the double-blinded phase.

Participants by arm

Arm	Count
Fazirsiran 25 mg Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses.	9
Fazirsiran 100 mg Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses.	8
Fazirsiran 200 mg Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses.	9
Placebo Participants with no fibrosis: Placebo administered on Day 1 and Week 4. Participants with fibrosis: Placebo administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses.	14
Total	40

Withdrawals & dropouts

Period	Reason	FG000	FG002	FG007
Double-Blind (DB) Period: Weeks 0 to 48	Adverse Event	0	1	0
Double-Blind (DB) Period: Weeks 0 to 48	Withdrawal by Subject	1	1	0
Open-Label (OL) Period: Weeks 48 to 196	Adverse Event	0	0	1

Baseline characteristics

Characteristic	Fazirsiran 25 mg	Total	Placebo	Fazirsiran 200 mg	Fazirsiran 100 mg
Age, Continuous	52.6 years STANDARD_DEVIATION 15.56	53.1 years STANDARD_DEVIATION 12.33	57.4 years STANDARD_DEVIATION 9.05	51.6 years STANDARD_DEVIATION 9.44	47.9 years STANDARD_DEVIATION 12.25
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	3 Participants	2 Participants	0 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants	37 Participants	12 Participants	9 Participants	7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Fibrosis Status at Screening Fibrosis at Screening	4 Participants	25 Participants	9 Participants	7 Participants	5 Participants
Fibrosis Status at Screening No fibrosis at Screening	5 Participants	15 Participants	5 Participants	2 Participants	3 Participants
Race/Ethnicity, Customized White	9 Participants	40 Participants	14 Participants	9 Participants	8 Participants
Sex: Female, Male Female	5 Participants	22 Participants	5 Participants	6 Participants	6 Participants
Sex: Female, Male Male	4 Participants	18 Participants	9 Participants	3 Participants	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	0 / 9	0 / 8	0 / 9	0 / 14	0 / 4	0 / 5	0 / 5	0 / 9
other Total, other adverse events	9 / 9	8 / 8	9 / 9	14 / 14	4 / 4	4 / 5	3 / 5	9 / 9
serious Total, serious adverse events	0 / 9	0 / 8	2 / 9	3 / 14	1 / 4	1 / 5	1 / 5	1 / 9

Outcome results

Primary

Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16

Time frame: Baseline, Week 16 (+/- 2 weeks)

Population: Full Analysis Set: All randomized participants who received at least one dose of study drug.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Fazirsiran 25 mg	Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16	-62.17 percentage change	Standard Error 4.279
Fazirsiran 100 mg	Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16	-85.39 percentage change	Standard Error 4.634
Fazirsiran 200 mg	Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16	-92.93 percentage change	Standard Error 4.341
Placebo	Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16	4.64 percentage change	Standard Error 3.211

p-value: <0.000195% CI: [-77.18, -56.45]Mixed model repeated measures (MMRM)

p-value: <0.000195% CI: [-100.72, -79.34]MMRM

p-value: <0.000195% CI: [-108.21, -86.94]MMRM

Secondary

Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)

PDLB=post-dose liver biopsy

Time frame: Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)

Population: Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 16 + 24 H	-7.3 U/L	Standard Deviation 11.93
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 16	-3.0 U/L	Standard Deviation 9.17
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	PDLB at Week 48	-10.5 U/L	Standard Deviation 10.47
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 28	-10.7 U/L	Standard Deviation 4.57
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 76	-7.3 U/L	Standard Deviation 3.06
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 88	-9.0 U/L	Standard Deviation 3.46
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 52	-1.5 U/L	Standard Deviation 12.31
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 40	-4.6 U/L	Standard Deviation 9.07
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 100	-9.0 U/L	Standard Deviation 2.83
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 112	-8.0 U/L	—
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 64	-9.8 U/L	Standard Deviation 8.5
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	End of Study	7.0 U/L	Standard Deviation 16.64
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 52	-6.0 U/L	Standard Deviation 7.39
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 16	-2.4 U/L	Standard Deviation 5.42
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 64	-14.3 U/L	Standard Deviation 8.88
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 100	-21.5 U/L	Standard Deviation 9.19
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 76	-14.8 U/L	Standard Deviation 9.07
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	PDLB at Week 96	-21.0 U/L	Standard Deviation 5.66
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 88	-18.5 U/L	Standard Deviation 9.19
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 28	-5.8 U/L	Standard Deviation 9.56
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	End of Study	-1.0 U/L	Standard Deviation 5.66
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 124	-18.0 U/L	Standard Deviation 4.24
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 40	-5.0 U/L	Standard Deviation 8.78
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	PDLB at Week 48	0.0 U/L	Standard Deviation 16
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 16 + 24 H	-3.8 U/L	Standard Deviation 3.59
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 112	-18.0 U/L	Standard Deviation 7.07
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 112	8.0 U/L	Standard Deviation 4.24
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 16	-8.4 U/L	Standard Deviation 15.88
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 16 + 24 H	-2.2 U/L	Standard Deviation 2.86
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 28	0.6 U/L	Standard Deviation 6.48
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 40	3.1 U/L	Standard Deviation 9.79
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	PDLB at Week 48	-2.2 U/L	Standard Deviation 5.31
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 52	12.3 U/L	Standard Deviation 33.8
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 64	-0.3 U/L	Standard Deviation 8.3
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 76	3.5 U/L	Standard Deviation 8.24
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 88	4.8 U/L	Standard Deviation 4.97
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	PDLB at Week 96	12.0 U/L	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 100	7.5 U/L	Standard Deviation 7.78
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 124	7.0 U/L	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 136	4.0 U/L	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 148	11.0 U/L	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Early Termination	-2.0 U/L	Standard Deviation 9.9
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	End of Study	-0.5 U/L	Standard Deviation 4.95
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 100	1.3 U/L	Standard Deviation 9.43
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 52	-0.4 U/L	Standard Deviation 4.44
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	PDLB at Week 48	3.3 U/L	Standard Deviation 7.71
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 40	-0.1 U/L	Standard Deviation 4.66
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 112	-0.3 U/L	Standard Deviation 6.43
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 28	1.0 U/L	Standard Deviation 6.91
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	End of Study	-0.2 U/L	Standard Deviation 5.45
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 124	5.0 U/L	Standard Deviation 11.53
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 16 + 24 H	0.8 U/L	Standard Deviation 5.31
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 136	8.3 U/L	Standard Deviation 17.9
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 16	1.7 U/L	Standard Deviation 6.6
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 88	6.2 U/L	Standard Deviation 7.76
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 76	7.7 U/L	Standard Deviation 8.85
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 148	4.3 U/L	Standard Deviation 14.98
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	PDLB at Week 96	10.0 U/L	Standard Deviation 12.73
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	PDLB at Week 72	-6.0 U/L	—
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 64	5.7 U/L	Standard Deviation 15.48
Placebo	Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)	Week 160	23.0 U/L	Standard Deviation 4.24

Secondary

Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS

PDLB=post-dose liver biopsy

Time frame: Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)

Population: Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 16 + 24 H	-9.7 U/L	Standard Deviation 8.62
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 16	-2.8 U/L	Standard Deviation 9.98
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	PDLB at Week 48	-10.5 U/L	Standard Deviation 16.62
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 28	0.6 U/L	Standard Deviation 12.29
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 76	-14.0 U/L	Standard Deviation 23.39
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 88	-14.7 U/L	Standard Deviation 21.13
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 52	-3.0 U/L	Standard Deviation 15.38
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 40	-1.1 U/L	Standard Deviation 15.51
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 100	-23.0 U/L	Standard Deviation 26.87
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 112	-4.0 U/L	—
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 64	-8.3 U/L	Standard Deviation 22.23
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	End of Study	1.8 U/L	Standard Deviation 10.4
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 52	-7.6 U/L	Standard Deviation 8.26
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 16	-4.3 U/L	Standard Deviation 6.5
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 64	-6.5 U/L	Standard Deviation 8.96
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 100	-11.5 U/L	Standard Deviation 17.68
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 76	-9.0 U/L	Standard Deviation 11.58
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	PDLB at Week 96	-11.5 U/L	Standard Deviation 13.44
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 88	-16.5 U/L	Standard Deviation 23.33
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 28	-4.9 U/L	Standard Deviation 6.88
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	End of Study	-6.0 U/L	Standard Deviation 0
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 124	-4.0 U/L	Standard Deviation 5.66
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 40	-7.1 U/L	Standard Deviation 6.36
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	PDLB at Week 48	-0.3 U/L	Standard Deviation 1.15
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 16 + 24 H	-1.0 U/L	Standard Deviation 2.16
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 112	-6.0 U/L	Standard Deviation 11.31
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 112	-2.0 U/L	Standard Deviation 4.24
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 16	-13.8 U/L	Standard Deviation 14.26
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 16 + 24 H	-11.7 U/L	Standard Deviation 14.83
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 28	-8.4 U/L	Standard Deviation 13.53
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 40	-8.3 U/L	Standard Deviation 11.38
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	PDLB at Week 48	-2.8 U/L	Standard Deviation 15.69
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 52	-3.9 U/L	Standard Deviation 9.36
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 64	0.4 U/L	Standard Deviation 15.66
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 76	0.5 U/L	Standard Deviation 11.5
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 88	3.0 U/L	Standard Deviation 21.25
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	PDLB at Week 96	2.0 U/L	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 100	-2.0 U/L	Standard Deviation 2.83
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 124	4.0 U/L	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 136	2.0 U/L	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 148	15.0 U/L	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Early Termination	-0.5 U/L	Standard Deviation 17.68
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	End of Study	5.0 U/L	Standard Deviation 9.9
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 100	8.8 U/L	Standard Deviation 12.04
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 52	1.9 U/L	Standard Deviation 6.01
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	PDLB at Week 48	1.2 U/L	Standard Deviation 2.56
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 40	1.6 U/L	Standard Deviation 7.43
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 112	5.0 U/L	Standard Deviation 13.75
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 28	0.7 U/L	Standard Deviation 5.51
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	End of Study	3.4 U/L	Standard Deviation 11.76
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 124	4.3 U/L	Standard Deviation 9.24
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 16 + 24 H	3.6 U/L	Standard Deviation 6.62
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 136	7.0 U/L	Standard Deviation 25.16
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 16	4.9 U/L	Standard Deviation 13.02
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 88	8.4 U/L	Standard Deviation 8.02
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 76	6.5 U/L	Standard Deviation 11.33
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 148	11.0 U/L	Standard Deviation 26.46
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	PDLB at Week 96	7.0 U/L	Standard Deviation 19.8
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	PDLB at Week 72	5.0 U/L	—
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 64	2.1 U/L	Standard Deviation 9.25
Placebo	Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS	Week 160	23.0 U/L	Standard Deviation 26.87

Secondary

Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS

PDLB=post-dose liver biopsy

Time frame: Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)

Population: Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 16 + 24 H	-7.7 U/L	Standard Deviation 11.59
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 16	-2.9 U/L	Standard Deviation 8.27
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	PDLB at Week 48	-12.0 U/L	Standard Deviation 10.42
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 28	-7.4 U/L	Standard Deviation 7.31
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 76	-6.3 U/L	Standard Deviation 4.73
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 88	-6.7 U/L	Standard Deviation 5.69
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 52	-2.1 U/L	Standard Deviation 9.89
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 40	-2.9 U/L	Standard Deviation 10.78
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 100	-7.5 U/L	Standard Deviation 2.12
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 112	-10.0 U/L	—
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 64	-8.8 U/L	Standard Deviation 10.24
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	End of Study	4.7 U/L	Standard Deviation 8.33
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 52	-0.9 U/L	Standard Deviation 8.46
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 16	-0.1 U/L	Standard Deviation 4.02
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 64	-10.3 U/L	Standard Deviation 10.4
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 100	-21.5 U/L	Standard Deviation 13.44
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 76	-10.3 U/L	Standard Deviation 8.85
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	PDLB at Week 96	-11.0 U/L	—
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 88	-16.5 U/L	Standard Deviation 12.02
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 28	-1.3 U/L	Standard Deviation 4.68
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	End of Study	1.5 U/L	Standard Deviation 6.36
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 124	-16.5 U/L	Standard Deviation 10.61
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 40	2.0 U/L	Standard Deviation 17.55
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	PDLB at Week 48	1.7 U/L	Standard Deviation 4.16
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 16 + 24 H	0.0 U/L	Standard Deviation 2.58
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 112	-19.0 U/L	Standard Deviation 14.14
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 112	0.5 U/L	Standard Deviation 0.71
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 16	1.1 U/L	Standard Deviation 6.1
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 16 + 24 H	0.3 U/L	Standard Deviation 3.93
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 28	10.2 U/L	Standard Deviation 27.92
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 40	2.9 U/L	Standard Deviation 8.25
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	PDLB at Week 48	-1.0 U/L	Standard Deviation 5.22
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 52	6.3 U/L	Standard Deviation 15.92
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 64	-0.7 U/L	Standard Deviation 4.42
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 76	3.2 U/L	Standard Deviation 5.78
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 88	3.8 U/L	Standard Deviation 8.29
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	PDLB at Week 96	2.0 U/L	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 100	1.5 U/L	Standard Deviation 2.12
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 124	-1.0 U/L	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 136	-2.0 U/L	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 148	2.0 U/L	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Early Termination	-1.5 U/L	Standard Deviation 4.95
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	End of Study	1.5 U/L	Standard Deviation 9.19
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 100	0.0 U/L	Standard Deviation 4.76
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 52	-0.9 U/L	Standard Deviation 2.93
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	PDLB at Week 48	1.2 U/L	Standard Deviation 6.4
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 40	-0.9 U/L	Standard Deviation 3.65
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 112	-2.0 U/L	Standard Deviation 7
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 28	0.1 U/L	Standard Deviation 5.49
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	End of Study	-0.2 U/L	Standard Deviation 3.96
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 124	2.7 U/L	Standard Deviation 9.29
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 16 + 24 H	-0.4 U/L	Standard Deviation 3.81
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 136	6.7 U/L	Standard Deviation 10.6
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 16	0.7 U/L	Standard Deviation 5.23
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 88	4.2 U/L	Standard Deviation 6.57
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 76	7.5 U/L	Standard Deviation 7.2
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 148	1.0 U/L	Standard Deviation 11.14
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	PDLB at Week 96	5.0 U/L	Standard Deviation 5.66
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	PDLB at Week 72	-3.0 U/L	—
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 64	1.9 U/L	Standard Deviation 7.7
Placebo	Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS	Week 160	10.5 U/L	Standard Deviation 0.71

Secondary

Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS

PDLB=post-dose liver biopsy

Time frame: Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)

Population: Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 52	-0.024 mg/dL	Standard Deviation 0.08
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 64	-0.008 mg/dL	Standard Deviation 0.081
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	End of Study	0.050 mg/dL	Standard Deviation 0.06
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 88	0.053 mg/dL	Standard Deviation 0.114
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 76	0.027 mg/dL	Standard Deviation 0.029
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 16 + 24 H	0.013 mg/dL	Standard Deviation 0.029
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 112	0.020 mg/dL	—
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 28	0.029 mg/dL	Standard Deviation 0.055
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 40	0.026 mg/dL	Standard Deviation 0.05
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 16	0.016 mg/dL	Standard Deviation 0.049
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 100	0.000 mg/dL	Standard Deviation 0.028
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 48	-0.005 mg/dL	Standard Deviation 0.041
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 124	-0.040 mg/dL	Standard Deviation 0.057
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 52	0.034 mg/dL	Standard Deviation 0.107
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 28	0.039 mg/dL	Standard Deviation 0.14
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	End of Study	0.010 mg/dL	Standard Deviation 0.028
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 88	0.070 mg/dL	Standard Deviation 0.014
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 112	0.025 mg/dL	Standard Deviation 0.049
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 64	0.053 mg/dL	Standard Deviation 0.061
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 100	0.010 mg/dL	Standard Deviation 0.014
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 48	-0.080 mg/dL	Standard Deviation 0.21
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 76	0.098 mg/dL	Standard Deviation 0.069
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 40	0.045 mg/dL	Standard Deviation 0.16
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 16	-0.006 mg/dL	Standard Deviation 0.095
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 16 + 24 H	0.055 mg/dL	Standard Deviation 0.157
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 96	0.030 mg/dL	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 112	0.055 mg/dL	Standard Deviation 0.035
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 100	0.050 mg/dL	Standard Deviation 0.028
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 16	0.005 mg/dL	Standard Deviation 0.094
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 16 + 24 H	-0.030 mg/dL	Standard Deviation 0.081
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 28	0.004 mg/dL	Standard Deviation 0.062
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 40	-0.005 mg/dL	Standard Deviation 0.063
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 48	0.007 mg/dL	Standard Deviation 0.087
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 52	0.015 mg/dL	Standard Deviation 0.052
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 64	-0.007 mg/dL	Standard Deviation 0.076
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 76	-0.033 mg/dL	Standard Deviation 0.073
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 88	-0.007 mg/dL	Standard Deviation 0.043
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 96	0.080 mg/dL	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 124	0.070 mg/dL	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 136	0.030 mg/dL	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 148	0.050 mg/dL	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Early Termination	0.005 mg/dL	Standard Deviation 0.007
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	End of Study	0.028 mg/dL	Standard Deviation 0.138
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 160	0.015 mg/dL	Standard Deviation 0.007
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 96	0.045 mg/dL	Standard Deviation 0.035
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 40	0.020 mg/dL	Standard Deviation 0.125
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 28	0.008 mg/dL	Standard Deviation 0.073
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 112	0.007 mg/dL	Standard Deviation 0.061
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 16 + 24 H	-0.028 mg/dL	Standard Deviation 0.041
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	End of Study	0.053 mg/dL	Standard Deviation 0.044
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 124	0.020 mg/dL	Standard Deviation 0.035
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 16	0.010 mg/dL	Standard Deviation 0.061
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 136	0.013 mg/dL	Standard Deviation 0.046
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 72	-46.2 mg/dL	—
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 100	0.018 mg/dL	Standard Deviation 0.052
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 76	0.027 mg/dL	Standard Deviation 0.057
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 64	-0.019 mg/dL	Standard Deviation 0.043
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 52	0.031 mg/dL	Standard Deviation 0.058
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 148	-0.003 mg/dL	Standard Deviation 0.09
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 88	0.012 mg/dL	Standard Deviation 0.026
Placebo	Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 48	-0.038 mg/dL	Standard Deviation 0.065

Secondary

Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS

PDLB=post-dose liver biopsy

Time frame: Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124,136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)

Population: Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 16 + 24 H	-3.7 U/L	Standard Deviation 16.8
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 16	2.8 U/L	Standard Deviation 11.48
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	PDLB at Week 48	-13.5 U/L	Standard Deviation 23.67
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 28	-3.5 U/L	Standard Deviation 11.99
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 76	-20.3 U/L	Standard Deviation 28.36
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 88	-17.0 U/L	Standard Deviation 29.51
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 52	7.3 U/L	Standard Deviation 36.39
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 40	5.3 U/L	Standard Deviation 31.24
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 100	-25.0 U/L	Standard Deviation 28.28
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 112	0.0 U/L	—
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 64	-16.0 U/L	Standard Deviation 13.22
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	End of Study	22.5 U/L	Standard Deviation 45.68
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 52	-4.3 U/L	Standard Deviation 11.13
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 16	-4.3 U/L	Standard Deviation 5.9
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 64	-13.0 U/L	Standard Deviation 14.14
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 100	-24.5 U/L	Standard Deviation 21.92
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 76	-13.3 U/L	Standard Deviation 15.48
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	PDLB at Week 96	-25.5 U/L	Standard Deviation 14.85
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 88	-19.0 U/L	Standard Deviation 25.46
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 28	-5.3 U/L	Standard Deviation 5.57
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	End of Study	-0.5 U/L	Standard Deviation 0.71
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 124	-50.4 U/L	Standard Deviation 2.6
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 40	-3.8 U/L	Standard Deviation 9.29
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	PDLB at Week 48	-5.3 U/L	Standard Deviation 4.16
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 16 + 24 H	-4.8 U/L	Standard Deviation 4.35
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 112	-21.5 U/L	Standard Deviation 9.19
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 112	5.5 U/L	Standard Deviation 4.95
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 16	-9.1 U/L	Standard Deviation 16.06
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 16 + 24 H	-4.3 U/L	Standard Deviation 4.93
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 28	-4.1 U/L	Standard Deviation 9.65
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 40	0.9 U/L	Standard Deviation 16.88
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	PDLB at Week 48	-5.3 U/L	Standard Deviation 10.17
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 52	6.8 U/L	Standard Deviation 27.79
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 64	2.7 U/L	Standard Deviation 19.04
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 76	-3.3 U/L	Standard Deviation 11.04
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 88	2.0 U/L	Standard Deviation 7.81
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	PDLB at Week 96	5.0 U/L	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 100	6.5 U/L	Standard Deviation 4.95
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 124	8.0 U/L	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 136	7.0 U/L	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 148	10.0 U/L	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Early Termination	5.0 U/L	Standard Deviation 4.24
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	End of Study	-19.5 U/L	Standard Deviation 27.58
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 100	-2.3 U/L	Standard Deviation 14.29
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 52	1.7 U/L	Standard Deviation 6.64
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	PDLB at Week 48	-0.5 U/L	Standard Deviation 10.48
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 40	0.6 U/L	Standard Deviation 7.69
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 112	4.3 U/L	Standard Deviation 10.41
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 28	0.6 U/L	Standard Deviation 8.47
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	End of Study	0.6 U/L	Standard Deviation 5.59
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 124	1.7 U/L	Standard Deviation 9.61
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 16 + 24 H	1.1 U/L	Standard Deviation 4.62
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 136	5.0 U/L	Standard Deviation 7.55
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 16	7.0 U/L	Standard Deviation 14.88
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 88	7.2 U/L	Standard Deviation 4.97
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 76	-0.3 U/L	Standard Deviation 10.19
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 148	-0.3 U/L	Standard Deviation 11.59
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	PDLB at Week 96	3.5 U/L	Standard Deviation 0.71
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	PDLB at Week 72	-3.0 U/L	—
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 64	9.3 U/L	Standard Deviation 22.13
Placebo	Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS	Week 160	3.0 U/L	Standard Deviation 4.24

Secondary

Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS

PDLB=post-dose liver biopsy

Time frame: Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)

Population: Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 16 + 24 H	0.047 ratio	Standard Deviation 0.111
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 16	-0.012 ratio	Standard Deviation 0.054
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	PDLB at Week 48	-0.038 ratio	Standard Deviation 0.054
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 28	-0.054 ratio	Standard Deviation 0.148
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 76	-0.033 ratio	Standard Deviation 0.049
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 88	-0.053 ratio	Standard Deviation 0.04
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 52	-0.094 ratio	Standard Deviation 0.139
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 40	-0.021 ratio	Standard Deviation 0.113
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 100	0.000 ratio	Standard Deviation 0.014
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 112	0.050 ratio	—
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 64	-0.038 ratio	Standard Deviation 0.089
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	End of Study	-0.115 ratio	Standard Deviation 0.17
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 52	-0.053 ratio	Standard Deviation 0.057
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 16	-0.006 ratio	Standard Deviation 0.093
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 64	-0.100 ratio	Standard Deviation 0.082
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 100	-0.225 ratio	Standard Deviation 0.163
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 76	-0.110 ratio	Standard Deviation 0.13
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	PDLB at Week 96	-0.195 ratio	Standard Deviation 0.134
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 88	-0.225 ratio	Standard Deviation 0.177
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 28	-0.059 ratio	Standard Deviation 0.109
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	End of Study	-0.045 ratio	Standard Deviation 0.049
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 124	-0.175 ratio	Standard Deviation 0.247
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 40	-0.024 ratio	Standard Deviation 0.099
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	PDLB at Week 48	-0.067 ratio	Standard Deviation 0.15
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 16 + 24 H	-0.085 ratio	Standard Deviation 0.093
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 112	-0.240 ratio	Standard Deviation 0.184
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 112	0.035 ratio	Standard Deviation 0.078
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 16	0.011 ratio	Standard Deviation 0.068
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 16 + 24 H	-0.017 ratio	Standard Deviation 0.117
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 28	-0.040 ratio	Standard Deviation 0.107
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 40	-0.022 ratio	Standard Deviation 0.125
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	PDLB at Week 48	-0.023 ratio	Standard Deviation 0.121
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 52	-0.034 ratio	Standard Deviation 0.076
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 64	-0.043 ratio	Standard Deviation 0.13
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 76	-0.065 ratio	Standard Deviation 0.136
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 88	-0.004 ratio	Standard Deviation 0.083
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	PDLB at Week 96	0.090 ratio	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 100	-0.020 ratio	Standard Deviation 0.099
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 124	0.050 ratio	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 136	0.070 ratio	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 148	0.080 ratio	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Early Termination	0.045 ratio	Standard Deviation 0.092
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	End of Study	-0.035 ratio	Standard Deviation 0.021
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 100	0.063 ratio	Standard Deviation 0.045
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 52	-0.002 ratio	Standard Deviation 0.076
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	PDLB at Week 48	0.022 ratio	Standard Deviation 0.048
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 40	0.034 ratio	Standard Deviation 0.143
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 112	0.047 ratio	Standard Deviation 0.083
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 28	-0.014 ratio	Standard Deviation 0.167
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	End of Study	-0.106 ratio	Standard Deviation 0.149
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 124	0.053 ratio	Standard Deviation 0.021
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 16 + 24 H	0.036 ratio	Standard Deviation 0.104
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 136	0.043 ratio	Standard Deviation 0.032
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 16	0.055 ratio	Standard Deviation 0.18
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 88	0.038 ratio	Standard Deviation 0.026
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 76	0.020 ratio	Standard Deviation 0.046
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 148	0.040 ratio	Standard Deviation 0.026
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	PDLB at Week 96	0.045 ratio	Standard Deviation 0.078
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	PDLB at Week 72	0.040 ratio	—
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 64	0.012 ratio	Standard Deviation 0.055
Placebo	Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 160	0.070 ratio	Standard Deviation 0.042

Secondary

Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS

PDLB=post-dose liver biopsy

Time frame: Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124,136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)

Population: Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 16	0.079 mg/dL	Standard Deviation 0.146
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 88	0.247 mg/dL	Standard Deviation 0.375
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 40	0.083 mg/dL	Standard Deviation 0.115
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 76	0.110 mg/dL	Standard Deviation 0.105
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 100	-0.040 mg/dL	Standard Deviation 0.099
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 112	-0.020 mg/dL	—
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 48	0.043 mg/dL	Standard Deviation 0.109
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	End of Study	0.170 mg/dL	Standard Deviation 0.123
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 16 + 24 H	0.060 mg/dL	Standard Deviation 0.075
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 28	0.109 mg/dL	Standard Deviation 0.149
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 52	-0.023 mg/dL	Standard Deviation 0.203
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 64	0.020 mg/dL	Standard Deviation 0.21
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 100	-0.055 mg/dL	Standard Deviation 0.106
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 124	-0.190 mg/dL	Standard Deviation 0.071
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 52	0.129 mg/dL	Standard Deviation 0.362
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 76	0.248 mg/dL	Standard Deviation 0.357
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 96	0.020 mg/dL	Standard Deviation 0.127
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 88	0.105 mg/dL	Standard Deviation 0.035
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 16 + 24 H	0.163 mg/dL	Standard Deviation 0.456
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 64	0.188 mg/dL	Standard Deviation 0.235
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 28	0.171 mg/dL	Standard Deviation 0.47
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 112	-0.010 mg/dL	Standard Deviation 0.269
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 40	0.164 mg/dL	Standard Deviation 0.437
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 16	0.098 mg/dL	Standard Deviation 0.369
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 48	-0.070 mg/dL	Standard Deviation 0.594
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	End of Study	0.050 mg/dL	Standard Deviation 0.113
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 112	0.100 mg/dL	Standard Deviation 0.141
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 64	0.006 mg/dL	Standard Deviation 0.208
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 16	-0.051 mg/dL	Standard Deviation 0.241
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 16 + 24 H	-0.040 mg/dL	Standard Deviation 0.182
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 28	0.053 mg/dL	Standard Deviation 0.23
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 40	0.017 mg/dL	Standard Deviation 0.092
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 48	0.098 mg/dL	Standard Deviation 0.252
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 52	0.086 mg/dL	Standard Deviation 0.165
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 76	-0.043 mg/dL	Standard Deviation 0.206
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 88	0.002 mg/dL	Standard Deviation 0.131
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 96	0.170 mg/dL	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 100	0.090 mg/dL	Standard Deviation 0.042
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 124	0.130 mg/dL	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 136	0.100 mg/dL	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 148	0.070 mg/dL	—
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Early Termination	-0.010 mg/dL	Standard Deviation 0.014
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	End of Study	0.025 mg/dL	Standard Deviation 0.205
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 100	0.003 mg/dL	Standard Deviation 0.203
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 40	0.062 mg/dL	Standard Deviation 0.434
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 28	0.012 mg/dL	Standard Deviation 0.272
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 16 + 24 H	-0.118 mg/dL	Standard Deviation 0.105
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 112	-0.060 mg/dL	Standard Deviation 0.249
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 16	-0.004 mg/dL	Standard Deviation 0.208
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	End of Study	0.154 mg/dL	Standard Deviation 0.082
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 124	-0.037 mg/dL	Standard Deviation 0.085
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 72	-0.420 mg/dL	—
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 136	0.003 mg/dL	Standard Deviation 0.185
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 64	-0.086 mg/dL	Standard Deviation 0.188
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 88	-0.050 mg/dL	Standard Deviation 0.131
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 76	-0.018 mg/dL	Standard Deviation 0.198
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 148	-0.087 mg/dL	Standard Deviation 0.199
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 96	0.065 mg/dL	Standard Deviation 0.035
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 52	0.099 mg/dL	Standard Deviation 0.23
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 48	-0.085 mg/dL	Standard Deviation 0.178
Placebo	Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 160	-0.090 mg/dL	Standard Deviation 0.028

Secondary

Absolute Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis

Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96.

Time frame: Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks)

Population: Biopsy Analysis Set: All randomized participants who received at least one dose of study drug and had at least one central read histology biopsy result.

Arm	Measure	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis	-68.914 nmol/g	Standard Deviation 80.725
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis	-150.145 nmol/g	Standard Deviation 196.675
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis	-11.953 nmol/g	Standard Deviation 18.602
Placebo	Absolute Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis	-7.038 nmol/g	Standard Deviation 47.041

Secondary

Absolute Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis

Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96.

Time frame: Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks)

Population: Biopsy Analysis Set: All randomized participants who received at least one dose of study drug and had at least one central read histology biopsy result.

Arm	Measure	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Absolute Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis	-20.427 nmol/g	Standard Deviation 15.042
Fazirsiran 100 mg	Absolute Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis	-109.747 nmol/g	Standard Deviation 135.114
Fazirsiran 200 mg	Absolute Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis	-17.418 nmol/g	Standard Deviation 4.86
Placebo	Absolute Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis	2.300 nmol/g	Standard Deviation 12.94

Secondary

Absolute Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis

Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96.

Time frame: Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks)

Population: Biopsy Analysis Set: All randomized participants who received at least one dose of study drug and had at least one central read histology biopsy result.

Arm	Measure	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Absolute Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis	-89.341 nmol/g	Standard Deviation 94.832
Fazirsiran 100 mg	Absolute Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis	-259.892 nmol/g	Standard Deviation 330.199
Fazirsiran 200 mg	Absolute Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis	-29.371 nmol/g	Standard Deviation 22.867
Placebo	Absolute Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis	-4.738 nmol/g	Standard Deviation 57.342

Secondary

Absolute Change in Serum Z-AAT Over Time Through EOS

PDLB=post-dose liver biopsy

Time frame: Baseline, Weeks 2, 4, 6, 16, 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)

Population: Full Analysis Set: All randomized participants who received at least one dose of study drug; participants with an assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 16	-158.650 μg/mL	Standard Deviation 50.266
Fazirsiran 25 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 4	-146.267 μg/mL	Standard Deviation 68.511
Fazirsiran 25 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	PDLB at Week 48	-189.850 μg/mL	Standard Deviation 64.556
Fazirsiran 25 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 40	-122.288 μg/mL	Standard Deviation 70.057
Fazirsiran 25 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 28	-123.288 μg/mL	Standard Deviation 62.112
Fazirsiran 25 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	End of Study	-42.750 μg/mL	Standard Deviation 7.089
Fazirsiran 25 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 100	-204.650 μg/mL	Standard Deviation 18.597
Fazirsiran 25 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 2	-125.511 μg/mL	Standard Deviation 59.955
Fazirsiran 25 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 6	-176.100 μg/mL	Standard Deviation 47.242
Fazirsiran 25 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 112	-233.000 μg/mL	—
Fazirsiran 25 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 88	-142.767 μg/mL	Standard Deviation 89.632
Fazirsiran 25 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 64	-187.325 μg/mL	Standard Deviation 94.397
Fazirsiran 25 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 76	-164.067 μg/mL	Standard Deviation 65.875
Fazirsiran 25 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 52	-116.188 μg/mL	Standard Deviation 72.983
Fazirsiran 100 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 88	-260.200 μg/mL	Standard Deviation 82.166
Fazirsiran 100 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 2	-156.714 μg/mL	Standard Deviation 58.127
Fazirsiran 100 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 4	-178.413 μg/mL	Standard Deviation 58.821
Fazirsiran 100 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 6	-192.719 μg/mL	Standard Deviation 65.087
Fazirsiran 100 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 16	-185.213 μg/mL	Standard Deviation 58.059
Fazirsiran 100 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 28	-174.275 μg/mL	Standard Deviation 57.293
Fazirsiran 100 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 40	-165.763 μg/mL	Standard Deviation 59.312
Fazirsiran 100 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	PDLB at Week 48	-150.900 μg/mL	Standard Deviation 17.521
Fazirsiran 100 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 52	-157.300 μg/mL	Standard Deviation 56.023
Fazirsiran 100 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 64	-191.150 μg/mL	Standard Deviation 80.589
Fazirsiran 100 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 76	-189.225 μg/mL	Standard Deviation 91.259
Fazirsiran 100 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	PDLB at Week 96	-271.100 μg/mL	Standard Deviation 90.793
Fazirsiran 100 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 100	-244.100 μg/mL	Standard Deviation 91.358
Fazirsiran 100 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 112	-263.100 μg/mL	Standard Deviation 91.358
Fazirsiran 100 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 124	-237.650 μg/mL	Standard Deviation 102.743
Fazirsiran 100 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	End of Study	-103.533 μg/mL	Standard Deviation 3.443
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 100	-187.650 μg/mL	Standard Deviation 3.323
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 52	-165.741 μg/mL	Standard Deviation 64.535
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 148	-89.1 μg/mL	—
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 6	-188.781 μg/mL	Standard Deviation 43.539
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 112	-182.550 μg/mL	Standard Deviation 3.182
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 88	-186.116 μg/mL	Standard Deviation 44.539
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	End of Study	-39.000 μg/mL	Standard Deviation 1.414
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 124	-183.000 μg/mL	—
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 64	-190.284 μg/mL	Standard Deviation 45.07
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 28	-175.136 μg/mL	Standard Deviation 52.838
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Early Termination	-192.240 μg/mL	Standard Deviation 81.657
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	PDLB at Week 96	-194.160 μg/mL	—
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 136	-183.300 μg/mL	—
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 40	-164.629 μg/mL	Standard Deviation 63.83
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 76	-177.060 μg/mL	Standard Deviation 49.718
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 16	-182.240 μg/mL	Standard Deviation 45.71
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 4	-181.389 μg/mL	Standard Deviation 41.857
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	PDLB at Week 48	-194.535 μg/mL	Standard Deviation 51.128
Fazirsiran 200 mg	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 2	-169.044 μg/mL	Standard Deviation 40.328
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 6	7.000 μg/mL	Standard Deviation 26.712
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	PDLB at Week 48	14.333 μg/mL	Standard Deviation 38.754
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 148	9.333 μg/mL	Standard Deviation 11.719
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 64	0.333 μg/mL	Standard Deviation 27.208
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	PDLB at Week 72	-6.00 μg/mL	—
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 160	7.500 μg/mL	Standard Deviation 9.192
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 76	-9.500 μg/mL	Standard Deviation 20.907
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 52	-13.643 μg/mL	Standard Deviation 36.527
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 4	-0.429 μg/mL	Standard Deviation 18.826
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 88	-1.800 μg/mL	Standard Deviation 28.49
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	PDLB at Week 96	-35.000 μg/mL	Standard Deviation 15.556
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 100	-60.725 μg/mL	Standard Deviation 84.824
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 2	16.929 μg/mL	Standard Deviation 37.723
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	End of Study	19.750 μg/mL	Standard Deviation 30.966
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 112	-22.333 μg/mL	Standard Deviation 22.679
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 124	-26.000 μg/mL	Standard Deviation 22.271
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 28	-0.500 μg/mL	Standard Deviation 25.035
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 16	10.286 μg/mL	Standard Deviation 29.374
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 40	1.429 μg/mL	Standard Deviation 20.137
Placebo	Absolute Change in Serum Z-AAT Over Time Through EOS	Week 136	-8.000 μg/mL	Standard Deviation 22.65

Secondary

Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran

PDLB=post-dose liver biopsy

Time frame: Baseline, Weeks 4, 16, 28, 40, 48, 52, 64, 76, 88, 96, 100, 112, 124, 136, 148 or Early Termination (up to 148 weeks)

Population: Safety Analysis Set: all participants who received at least one dose of fazirsiran; participants with an assessment at given time point

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Fazirsiran 25 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 76	0 Participants
Fazirsiran 25 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 88	0 Participants
Fazirsiran 25 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 28	0 Participants
Fazirsiran 25 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 100	0 Participants
Fazirsiran 25 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 4	0 Participants
Fazirsiran 25 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 112	0 Participants
Fazirsiran 25 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 40	0 Participants
Fazirsiran 25 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	PDLB at Week 48	0 Participants
Fazirsiran 25 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Baseline	0 Participants
Fazirsiran 25 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 52	0 Participants
Fazirsiran 25 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 16	0 Participants
Fazirsiran 25 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 64	0 Participants
Fazirsiran 100 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 16	1 Participants
Fazirsiran 100 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 76	1 Participants
Fazirsiran 100 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Baseline	2 Participants
Fazirsiran 100 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 124	0 Participants
Fazirsiran 100 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 88	0 Participants
Fazirsiran 100 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 40	2 Participants
Fazirsiran 100 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 28	2 Participants
Fazirsiran 100 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 4	1 Participants
Fazirsiran 100 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 100	0 Participants
Fazirsiran 100 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 52	1 Participants
Fazirsiran 100 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 64	0 Participants
Fazirsiran 100 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 112	0 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Early Termination	0 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Baseline	2 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 4	2 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 16	2 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 28	1 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 40	2 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	PDLB at Week 48	0 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 52	0 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 64	0 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 76	0 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 88	0 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	PDLB at Week 96	0 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 100	0 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 112	1 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 124	1 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 148	1 Participants
Fazirsiran 200 mg	Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran	Week 136	1 Participants

Secondary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase

An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with this treatment. A serious adverse event (SAE) is an AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction. TEAEs/TESAEs are defined as those AEs that first occurred or worsened in severity following dose administration through end of study (EOS) or Early Termination or first dose of open-label phase fazirsiran.

Time frame: Double Blind Phase (up to Week 48): dose administration through end of study (EOS) or Early Termination or first dose of open-label phase fazirsiran.

Population: Safety Analysis Set: All participants who receive at least one dose of study drug.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Severity: Moderate	6 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TESAEs	0 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Relationship: Possibly Related	2 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Severity: Severe	0 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs	9 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAE at Injection Site	1 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs Leading to Withdrawal of Study Drug	0 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Relationship: Possibly or Probably	2 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs Leading to Study Termination	0 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs Leading to Death	0 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Relationship: Not Related	7 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Relationship: Probably Related	0 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Severity: Mild	3 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Severity: Mild	2 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Severity: Moderate	6 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAE at Injection Site	1 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs Leading to Study Termination	0 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs	8 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Severity: Severe	0 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TESAEs	0 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Relationship: Not Related	4 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Relationship: Probably Related	1 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Relationship: Possibly Related	3 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs Leading to Death	0 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs Leading to Withdrawal of Study Drug	0 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Relationship: Possibly or Probably	4 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs Leading to Withdrawal of Study Drug	1 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs	9 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TESAEs	2 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs Leading to Study Termination	1 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs Leading to Death	0 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Severity: Mild	1 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Severity: Moderate	6 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Severity: Severe	2 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Relationship: Not Related	5 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Relationship: Possibly Related	1 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Relationship: Probably Related	3 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Relationship: Possibly or Probably	4 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAE at Injection Site	2 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Relationship: Possibly Related	8 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs Leading to Death	0 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs Leading to Study Termination	0 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs	14 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Relationship: Probably Related	0 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs Leading to Withdrawal of Study Drug	0 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Severity: Severe	3 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAE at Injection Site	2 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Relationship: Possibly or Probably	8 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Relationship: Not Related	6 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Severity: Moderate	6 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TEAEs by Worst Severity: Mild	5 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase	TESAEs	3 Participants

Secondary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase

Time frame: From dose administration of the first dose of open-label phase fazirsiran through EOS or Early Termination (up to Week 196).

Population: Safety Analysis Set: All participants who receive at least one dose of study drug.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs	4 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TESAEs	1 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs Leading to Withdrawal of Study Drug	0 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs Leading to Study Termination	0 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs Leading to Death	0 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Severity: Mild	3 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Severity: Moderate	0 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Severity: Severe	1 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Relationship: Not Related	2 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Relationship: Possibly Related	2 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Relationship: Probably Related	0 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Relationship: Possibly or Probably	2 Participants
Fazirsiran 25 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAE at Injection Site	1 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs Leading to Study Termination	0 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAE at Injection Site	1 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Relationship: Probably Related	1 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Severity: Severe	1 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs Leading to Withdrawal of Study Drug	0 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs	4 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Relationship: Possibly Related	3 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Relationship: Not Related	0 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Severity: Mild	2 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs Leading to Death	0 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TESAEs	1 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Relationship: Possibly or Probably	4 Participants
Fazirsiran 100 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Severity: Moderate	1 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Relationship: Probably Related	0 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs Leading to Study Termination	0 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs Leading to Death	0 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAE at Injection Site	0 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Severity: Mild	0 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Severity: Moderate	3 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Relationship: Possibly or Probably	0 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Severity: Severe	0 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Relationship: Not Related	3 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Relationship: Possibly Related	0 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs	3 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TESAEs	1 Participants
Fazirsiran 200 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs Leading to Withdrawal of Study Drug	0 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Relationship: Possibly Related	2 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Severity: Severe	1 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Relationship: Probably Related	0 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs	9 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Severity: Moderate	1 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Severity: Mild	7 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs Leading to Study Termination	1 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs Leading to Withdrawal of Study Drug	1 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TESAEs	1 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Relationship: Not Related	7 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAE at Injection Site	0 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs by Worst Relationship: Possibly or Probably	2 Participants
Placebo	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase	TEAEs Leading to Death	0 Participants

Secondary

Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis

The METAVIR scoring system is a system used to assess the extent of inflammation and fibrosis by histopathological evaluation in a liver biopsy. The stage represents the amount of fibrosis or scarring: 0= no fibrosis; 1=portal fibrosis without septa; 2=portal fibrosis with few septa; 3=numerous septa without cirrhosis; 4=cirrhosis. A higher score indicates a worse condition.

Time frame: Baseline, Post-dose at Weeks 48 (+/- 2 weeks) or Week 72 (+/- 4 weeks) or Week 96 (+/- 4 weeks)

Population: Biopsy Analysis Set: All randomized participants who received at least one dose of study drug and had at least one central read histology biopsy result; participants eligible to meet the defined criteria. (For example, participants with baseline METAVIR fibrosis score 0 are not eligible for improvement; participants with baseline METAVIR fibrosis score 4 are not eligible for worsening.)

Arm	Measure	Group	Value (NUMBER)
Fazirsiran 25 mg	Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis	>= 1-point improvement from baseline	66.7 percentage of participants
Fazirsiran 25 mg	Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis	>= 1-point worsening from baseline	25.0 percentage of participants
Fazirsiran 25 mg	Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis	no change from baseline	25.0 percentage of participants
Fazirsiran 100 mg	Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis	>= 1-point improvement from baseline	40.0 percentage of participants
Fazirsiran 100 mg	Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis	>= 1-point worsening from baseline	0.0 percentage of participants
Fazirsiran 100 mg	Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis	no change from baseline	60.0 percentage of participants
Fazirsiran 200 mg	Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis	no change from baseline	14.3 percentage of participants
Fazirsiran 200 mg	Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis	>= 1-point improvement from baseline	50.0 percentage of participants
Fazirsiran 200 mg	Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis	>= 1-point worsening from baseline	42.9 percentage of participants
Placebo	Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis	>= 1-point improvement from baseline	37.5 percentage of participants
Placebo	Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis	>= 1-point worsening from baseline	22.2 percentage of participants
Placebo	Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis	no change from baseline	44.4 percentage of participants

Secondary

Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS

PDLB=post-dose liver biopsy

Time frame: Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)

Population: Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 16 + 24 H	-8.9 percentage change	Standard Deviation 6.1
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 16	-0.5 percentage change	Standard Deviation 12.8
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	PDLB at Week 48	-8.5 percentage change	Standard Deviation 13.9
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 28	5.5 percentage change	Standard Deviation 20.1
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 76	-11.2 percentage change	Standard Deviation 18.2
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 88	-12.5 percentage change	Standard Deviation 15.9
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 52	0.1 percentage change	Standard Deviation 17
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 40	2.0 percentage change	Standard Deviation 16.9
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 100	-19.4 percentage change	Standard Deviation 19.4
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 112	-5.6 percentage change	—
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 64	-5.6 percentage change	Standard Deviation 18.4
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	End of Study	7.8 percentage change	Standard Deviation 18.2
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 52	-9.7 percentage change	Standard Deviation 11.7
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 16	-5.6 percentage change	Standard Deviation 8.7
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 64	-8.3 percentage change	Standard Deviation 10.8
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 100	-13.6 percentage change	Standard Deviation 21.2
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 76	-11.4 percentage change	Standard Deviation 13.5
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	PDLB at Week 96	-13.9 percentage change	Standard Deviation 15.7
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 88	-19.6 percentage change	Standard Deviation 27.8
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 28	-6.4 percentage change	Standard Deviation 9.3
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	End of Study	-7.2 percentage change	Standard Deviation 1.8
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 124	-4.8 percentage change	Standard Deviation 6.7
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 40	-9.3 percentage change	Standard Deviation 8.2
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	PDLB at Week 48	-0.4 percentage change	Standard Deviation 1.5
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 16 + 24 H	-1.2 percentage change	Standard Deviation 2.8
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 112	-6.9 percentage change	Standard Deviation 13.8
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 112	-2.4 percentage change	Standard Deviation 5.5
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 16	-17.7 percentage change	Standard Deviation 16
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 16 + 24 H	-14.8 percentage change	Standard Deviation 16.8
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 28	-10.5 percentage change	Standard Deviation 16.1
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 40	-10.4 percentage change	Standard Deviation 14.9
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	PDLB at Week 48	-3.3 percentage change	Standard Deviation 23.5
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 52	-4.9 percentage change	Standard Deviation 13.5
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 64	-0.2 percentage change	Standard Deviation 22.5
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 76	0.7 percentage change	Standard Deviation 18.1
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 88	3.2 percentage change	Standard Deviation 30.3
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	PDLB at Week 96	2.9 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 100	-2.5 percentage change	Standard Deviation 3.6
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 124	5.8 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 136	2.9 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 148	21.7 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Early Termination	4.6 percentage change	Standard Deviation 26.1
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	End of Study	7.1 percentage change	Standard Deviation 13.9
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 100	10.1 percentage change	Standard Deviation 13.4
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 52	2.7 percentage change	Standard Deviation 8.3
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	PDLB at Week 48	1.7 percentage change	Standard Deviation 3.7
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 40	2.2 percentage change	Standard Deviation 10.4
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 112	5.7 percentage change	Standard Deviation 15.6
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 28	1.0 percentage change	Standard Deviation 7.2
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	End of Study	5.3 percentage change	Standard Deviation 12.3
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 124	4.7 percentage change	Standard Deviation 10.5
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 16 + 24 H	5.9 percentage change	Standard Deviation 10
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 136	6.8 percentage change	Standard Deviation 29.3
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 16	5.8 percentage change	Standard Deviation 14.7
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 88	10.6 percentage change	Standard Deviation 9.5
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 76	8.0 percentage change	Standard Deviation 13.3
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 148	11.5 percentage change	Standard Deviation 30.8
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	PDLB at Week 96	7.6 percentage change	Standard Deviation 22.6
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	PDLB at Week 72	7.1 percentage change	—
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 64	3.9 percentage change	Standard Deviation 11
Placebo	Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS	Week 160	26.0 percentage change	Standard Deviation 30

Secondary

Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS

PDLB=post-dose liver biopsy

Time frame: Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)

Population: Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 52	-1.6 percentage change	Standard Deviation 32.9
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 40	-11.2 percentage change	Standard Deviation 21.4
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 76	-20.0 percentage change	Standard Deviation 7
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	PDLB at Week 48	-21.7 percentage change	Standard Deviation 19.1
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	End of Study	14.1 percentage change	Standard Deviation 38.7
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 112	-27.6 percentage change	—
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 16 + 24 H	-15.7 percentage change	Standard Deviation 24.8
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 100	-31.0 percentage change	Standard Deviation 9.8
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 88	-24.1 percentage change	Standard Deviation 0
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 28	-27.4 percentage change	Standard Deviation 8.5
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 16	-9.6 percentage change	Standard Deviation 20.1
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 64	-22.3 percentage change	Standard Deviation 20.3
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 40	-13.0 percentage change	Standard Deviation 24
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 16 + 24 H	-9.7 percentage change	Standard Deviation 8.9
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 16	-4.3 percentage change	Standard Deviation 19.9
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 28	-12.4 percentage change	Standard Deviation 25.1
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	PDLB at Week 48	-1.2 percentage change	Standard Deviation 38.2
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 52	-15.2 percentage change	Standard Deviation 18.1
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 64	-33.3 percentage change	Standard Deviation 15.5
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 76	-33.7 percentage change	Standard Deviation 16.2
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 88	-39.8 percentage change	Standard Deviation 15.9
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	PDLB at Week 96	-45.7 percentage change	Standard Deviation 7.5
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 100	-46.4 percentage change	Standard Deviation 15.2
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 112	-38.9 percentage change	Standard Deviation 11.3
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 124	-39.3 percentage change	Standard Deviation 5.1
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	End of Study	-6.8 percentage change	Standard Deviation 34.6
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 148	55.0 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 64	4.4 percentage change	Standard Deviation 35.8
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 76	24.6 percentage change	Standard Deviation 43.6
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 88	28.2 percentage change	Standard Deviation 32.6
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Early Termination	-10.3 percentage change	Standard Deviation 65
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	PDLB at Week 96	60.0 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 16 + 24 H	-10.8 percentage change	Standard Deviation 17.6
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 16	-15.3 percentage change	Standard Deviation 16.2
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 100	38.1 percentage change	Standard Deviation 38.1
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 112	41.4 percentage change	Standard Deviation 19.2
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	End of Study	-8.4 percentage change	Standard Deviation 15
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 124	35.0 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 40	4.0 percentage change	Standard Deviation 20
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 136	20.0 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	PDLB at Week 48	-4.8 percentage change	Standard Deviation 20.5
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 52	14.5 percentage change	Standard Deviation 28.5
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 28	2.0 percentage change	Standard Deviation 29.3
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 100	9.9 percentage change	Standard Deviation 24.1
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 16	5.8 percentage change	Standard Deviation 16.1
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	End of Study	4.7 percentage change	Standard Deviation 23.3
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 64	11.0 percentage change	Standard Deviation 29.3
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	PDLB at Week 72	-14.3 percentage change	—
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 148	25.5 percentage change	Standard Deviation 61.4
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 136	40.1 percentage change	Standard Deviation 79.4
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 76	26.3 percentage change	Standard Deviation 34.1
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 16 + 24 H	0.5 percentage change	Standard Deviation 13.3
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 160	88.8 percentage change	Standard Deviation 3
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 112	3.3 percentage change	Standard Deviation 24.7
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 88	20.7 percentage change	Standard Deviation 28.6
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 52	-1.4 percentage change	Standard Deviation 14.8
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	PDLB at Week 48	5.9 percentage change	Standard Deviation 15.2
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	PDLB at Week 96	44.8 percentage change	Standard Deviation 58.7
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 124	25.2 percentage change	Standard Deviation 49.4
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 40	2.9 percentage change	Standard Deviation 18.3
Placebo	Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS	Week 28	6.4 percentage change	Standard Deviation 21.9

Secondary

Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS

PDLB=post-dose liver biopsy

Time frame: Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)

Population: Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 16	-8.3 percentage change	Standard Deviation 20
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 112	-34.5 percentage change	—
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 40	-4.7 percentage change	Standard Deviation 26.9
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 64	-20.5 percentage change	Standard Deviation 23.3
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 88	-16.4 percentage change	Standard Deviation 10.1
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 76	-17.1 percentage change	Standard Deviation 12.7
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	PDLB at Week 48	-27.1 percentage change	Standard Deviation 20.1
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 28	-19.3 percentage change	Standard Deviation 19.3
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 16 + 24 H	-16.9 percentage change	Standard Deviation 24.2
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 100	-24.6 percentage change	Standard Deviation 9.1
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 52	-4.1 percentage change	Standard Deviation 27.2
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	End of Study	13.7 percentage change	Standard Deviation 24.6
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	PDLB at Week 48	6.0 percentage change	Standard Deviation 12.5
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 112	-35.1 percentage change	Standard Deviation 18.7
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 52	1.9 percentage change	Standard Deviation 20.9
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	PDLB at Week 96	-26.8 percentage change	—
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 64	-21.4 percentage change	Standard Deviation 15.4
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 88	-30.6 percentage change	Standard Deviation 15.7
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 76	-22.2 percentage change	Standard Deviation 13.9
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 16 + 24 H	0.4 percentage change	Standard Deviation 7.8
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	End of Study	10.5 percentage change	Standard Deviation 35.1
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 124	-31.0 percentage change	Standard Deviation 12.8
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 28	-0.9 percentage change	Standard Deviation 14.5
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 40	10.6 percentage change	Standard Deviation 43.4
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 16	2.6 percentage change	Standard Deviation 16.4
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 100	-40.5 percentage change	Standard Deviation 15.8
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 100	5.6 percentage change	Standard Deviation 7.9
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 112	2.5 percentage change	Standard Deviation 3.5
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 16	3.5 percentage change	Standard Deviation 22.5
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 16 + 24 H	1.5 percentage change	Standard Deviation 17.6
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 28	26.8 percentage change	Standard Deviation 68.8
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 40	8.3 percentage change	Standard Deviation 21.7
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	PDLB at Week 48	-2.0 percentage change	Standard Deviation 16.2
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 52	17.3 percentage change	Standard Deviation 40.3
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 64	-2.6 percentage change	Standard Deviation 16.8
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 76	11.9 percentage change	Standard Deviation 22.6
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 88	18.1 percentage change	Standard Deviation 34.7
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	PDLB at Week 96	7.4 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 124	-3.7 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 136	-7.4 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 148	7.4 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Early Termination	-7.3 percentage change	Standard Deviation 26.9
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	End of Study	-2.7 percentage change	Standard Deviation 31.5
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	PDLB at Week 96	31.9 percentage change	Standard Deviation 39.8
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	PDLB at Week 48	3.4 percentage change	Standard Deviation 19.2
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 40	-1.0 percentage change	Standard Deviation 11.4
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 28	3.2 percentage change	Standard Deviation 17.4
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 100	5.2 percentage change	Standard Deviation 16.3
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 16 + 24 H	0.1 percentage change	Standard Deviation 9.8
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	End of Study	0.7 percentage change	Standard Deviation 17.1
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 124	25.6 percentage change	Standard Deviation 53.1
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 16	2.5 percentage change	Standard Deviation 14.3
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 136	39.6 percentage change	Standard Deviation 70.4
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 112	2.8 percentage change	Standard Deviation 27
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 76	30.3 percentage change	Standard Deviation 32.8
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	PDLB at Week 72	-5.9 percentage change	—
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 64	9.5 percentage change	Standard Deviation 21.6
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 148	21.8 percentage change	Standard Deviation 56.6
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 88	21.1 percentage change	Standard Deviation 29.6
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 52	-2.8 percentage change	Standard Deviation 9.7
Placebo	Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS	Week 160	55.2 percentage change	Standard Deviation 25.7

Secondary

Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS

PDLB=post-dose liver biopsy

Time frame: Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)

Population: Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 16 + 24 H	11.0 percentage change	Standard Deviation 16.4
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 16	5.9 percentage change	Standard Deviation 30.1
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 100	-3.8 percentage change	Standard Deviation 16.3
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 88	18.2 percentage change	Standard Deviation 35
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 76	9.9 percentage change	Standard Deviation 7.4
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 64	4.4 percentage change	Standard Deviation 39.7
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 52	-12.1 percentage change	Standard Deviation 34.3
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 48	2.9 percentage change	Standard Deviation 19.5
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 40	17.9 percentage change	Standard Deviation 27.5
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	End of Study	34.3 percentage change	Standard Deviation 45.6
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 112	15.4 percentage change	—
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 28	19.0 percentage change	Standard Deviation 28.3
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 16 + 24 H	22.4 percentage change	Standard Deviation 50.9
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	End of Study	5.4 percentage change	Standard Deviation 14.7
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 16	1.5 percentage change	Standard Deviation 31.2
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 28	15.4 percentage change	Standard Deviation 37.3
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 40	16.7 percentage change	Standard Deviation 44.9
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 48	-9.9 percentage change	Standard Deviation 63
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 52	17.8 percentage change	Standard Deviation 35.1
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 64	18.9 percentage change	Standard Deviation 26.7
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 76	33.4 percentage change	Standard Deviation 20.2
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 88	24.9 percentage change	Standard Deviation 14
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 96	7.5 percentage change	—
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 100	4.3 percentage change	Standard Deviation 6.1
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 112	5.3 percentage change	Standard Deviation 13.7
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 124	-10.0 percentage change	Standard Deviation 14.1
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 112	46.4 percentage change	Standard Deviation 37.3
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 88	-3.3 percentage change	Standard Deviation 30.3
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 16 + 24 H	-0.1 percentage change	Standard Deviation 33
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 64	8.2 percentage change	Standard Deviation 37.3
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 96	53.3 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 100	37.0 percentage change	Standard Deviation 13.7
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 16	29.1 percentage change	Standard Deviation 67.6
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 52	25.1 percentage change	Standard Deviation 47
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 48	19.3 percentage change	Standard Deviation 48.7
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	End of Study	96.1 percentage change	Standard Deviation 185.5
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 124	46.7 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 28	21.2 percentage change	Standard Deviation 61.9
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 76	-5.4 percentage change	Standard Deviation 30
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Early Termination	2.4 percentage change	Standard Deviation 3.4
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 148	33.3 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 40	15.5 percentage change	Standard Deviation 47.6
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 136	20.0 percentage change	—
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 160	6.7 percentage change	Standard Deviation 4.6
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 40	14.3 percentage change	Standard Deviation 50.2
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 48	-11.9 percentage change	Standard Deviation 23.9
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 148	3.4 percentage change	Standard Deviation 38.5
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 100	7.5 percentage change	Standard Deviation 23.2
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 52	19.6 percentage change	Standard Deviation 38.5
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 64	-8.6 percentage change	Standard Deviation 16.7
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 72	-46.2 percentage change	—
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 136	7.2 percentage change	Standard Deviation 18.3
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 76	11.4 percentage change	Standard Deviation 21.5
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 88	5.6 percentage change	Standard Deviation 12.1
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 112	4.1 percentage change	Standard Deviation 22.5
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 96	17.1 percentage change	Standard Deviation 10
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 16	15.1 percentage change	Standard Deviation 58.9
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	End of Study	40.8 percentage change	Standard Deviation 46.7
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 16 + 24 H	-8.8 percentage change	Standard Deviation 17
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 28	10.1 percentage change	Standard Deviation 44.6
Placebo	Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS	Week 124	7.7 percentage change	Standard Deviation 13.3

Secondary

Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS

PDLB=post-dose liver biopsy

Time frame: Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)

Population: Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 16 + 24 H	0.8 percentage change	Standard Deviation 32.2
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 16	5.9 percentage change	Standard Deviation 18.9
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	PDLB at Week 48	-8.9 percentage change	Standard Deviation 36.3
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 28	-2.2 percentage change	Standard Deviation 21.5
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 76	-22.2 percentage change	Standard Deviation 13.6
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 88	13.7 percentage change	Standard Deviation 21.1
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 52	26.7 percentage change	Standard Deviation 69.5
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 40	14.4 percentage change	Standard Deviation 52.4
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 100	-23.4 percentage change	Standard Deviation 11.7
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 112	0.0 percentage change	—
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 64	-23.0 percentage change	Standard Deviation 6.7
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	End of Study	39.2 percentage change	Standard Deviation 78.5
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 52	-3.5 percentage change	Standard Deviation 25.1
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 16	-9.7 percentage change	Standard Deviation 12.7
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 64	-22.8 percentage change	Standard Deviation 17.8
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 100	-38.0 percentage change	Standard Deviation 24.8
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 76	-23.1 percentage change	Standard Deviation 18.9
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	PDLB at Week 96	-42.0 percentage change	Standard Deviation 11.2
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 88	-26.8 percentage change	Standard Deviation 34.7
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 28	-12.0 percentage change	Standard Deviation 11.7
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	End of Study	-2.2 percentage change	Standard Deviation 3.1
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 124	-50.4 percentage change	Standard Deviation 2.6
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 40	-6.4 percentage change	Standard Deviation 18.3
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	PDLB at Week 48	-13.3 percentage change	Standard Deviation 7.2
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 16 + 24 H	-9.1 percentage change	Standard Deviation 8.6
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 112	-36.5 percentage change	Standard Deviation 3.4
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 112	28.4 percentage change	Standard Deviation 23.5
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 16	-14.8 percentage change	Standard Deviation 18.5
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 16 + 24 H	-13.2 percentage change	Standard Deviation 13.6
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 28	-3.2 percentage change	Standard Deviation 22.2
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 40	-1.7 percentage change	Standard Deviation 31.6
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	PDLB at Week 48	-10.4 percentage change	Standard Deviation 30.9
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 52	6.2 percentage change	Standard Deviation 35.2
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 64	20.7 percentage change	Standard Deviation 69.3
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 76	-0.9 percentage change	Standard Deviation 38.4
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 88	15.6 percentage change	Standard Deviation 39.5
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	PDLB at Week 96	25.0 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 100	33.8 percentage change	Standard Deviation 22.9
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 124	40.0 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 136	35.0 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 148	50.0 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Early Termination	30.7 percentage change	Standard Deviation 32.1
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	End of Study	-17.1 percentage change	Standard Deviation 24.2
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 100	6.1 percentage change	Standard Deviation 24.2
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 52	5.1 percentage change	Standard Deviation 15.3
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	PDLB at Week 48	8.1 percentage change	Standard Deviation 17.6
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 40	7.4 percentage change	Standard Deviation 14.4
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 112	16.0 percentage change	Standard Deviation 32.9
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 28	6.8 percentage change	Standard Deviation 21.5
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	End of Study	6.7 percentage change	Standard Deviation 18.8
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 124	8.1 percentage change	Standard Deviation 28.7
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 16 + 24 H	4.7 percentage change	Standard Deviation 15.4
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 136	18.0 percentage change	Standard Deviation 23.4
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 16	13.9 percentage change	Standard Deviation 31
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 88	17.9 percentage change	Standard Deviation 15.1
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 76	9.5 percentage change	Standard Deviation 13.3
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 148	2.9 percentage change	Standard Deviation 33.3
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	PDLB at Week 96	11.9 percentage change	Standard Deviation 2.7
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	PDLB at Week 72	-6.7 percentage change	—
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 64	13.1 percentage change	Standard Deviation 24.9
Placebo	Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS	Week 160	10.0 percentage change	Standard Deviation 14.1

Secondary

Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS

PDLB=post-dose liver biopsy

Time frame: Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)

Population: Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 64	-3.2 percentage change	Standard Deviation 7.9
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 100	0.0 percentage change	Standard Deviation 1.4
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 76	-2.8 percentage change	Standard Deviation 4
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	End of Study	-9.1 percentage change	Standard Deviation 12.7
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 88	-4.7 percentage change	Standard Deviation 3.1
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 28	-3.9 percentage change	Standard Deviation 11.8
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 16 + 24 H	4.4 percentage change	Standard Deviation 10.3
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 40	-1.2 percentage change	Standard Deviation 9.6
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	PDLB at Week 48	-3.2 percentage change	Standard Deviation 4.7
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 16	-1.0 percentage change	Standard Deviation 4.8
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 112	4.9 percentage change	—
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 52	-7.7 percentage change	Standard Deviation 10.2
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 124	-13.4 percentage change	Standard Deviation 18.9
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 64	-8.4 percentage change	Standard Deviation 7.1
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 40	-1.6 percentage change	Standard Deviation 7.8
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 16 + 24 H	-7.0 percentage change	Standard Deviation 6.9
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	End of Study	-4.3 percentage change	Standard Deviation 4.9
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	PDLB at Week 96	-15.6 percentage change	Standard Deviation 9.2
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 112	-19.1 percentage change	Standard Deviation 12.9
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 76	-8.8 percentage change	Standard Deviation 9.9
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 52	-4.7 percentage change	Standard Deviation 4.9
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 88	-17.9 percentage change	Standard Deviation 12.5
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	PDLB at Week 48	-5.5 percentage change	Standard Deviation 13.3
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 16	-0.7 percentage change	Standard Deviation 7.7
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 28	-4.9 percentage change	Standard Deviation 8.5
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 100	-18.0 percentage change	Standard Deviation 11.3
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	End of Study	-3.6 percentage change	Standard Deviation 2
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 16 + 24 H	-1.0 percentage change	Standard Deviation 10.2
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 16	1.2 percentage change	Standard Deviation 6.4
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 28	-3.3 percentage change	Standard Deviation 9.1
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 40	-1.6 percentage change	Standard Deviation 11.3
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	PDLB at Week 48	-1.5 percentage change	Standard Deviation 10.3
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 52	-2.9 percentage change	Standard Deviation 6.3
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 64	-3.2 percentage change	Standard Deviation 11.4
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 76	-5.3 percentage change	Standard Deviation 11.8
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 88	-0.3 percentage change	Standard Deviation 8
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	PDLB at Week 96	9.0 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 100	-1.8 percentage change	Standard Deviation 9.6
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 112	3.5 percentage change	Standard Deviation 7.7
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 124	5.0 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 136	7.0 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 148	8.0 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Early Termination	4.8 percentage change	Standard Deviation 9.4
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 148	3.9 percentage change	Standard Deviation 2.5
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 100	6.2 percentage change	Standard Deviation 4.5
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	PDLB at Week 48	2.2 percentage change	Standard Deviation 4.8
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 40	3.7 percentage change	Standard Deviation 13
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 160	7.0 percentage change	Standard Deviation 4.3
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 112	4.7 percentage change	Standard Deviation 8.4
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 28	1.2 percentage change	Standard Deviation 8.7
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 16	2.6 percentage change	Standard Deviation 8.6
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 124	5.3 percentage change	Standard Deviation 2.1
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 16 + 24 H	3.5 percentage change	Standard Deviation 9.9
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 76	2.0 percentage change	Standard Deviation 4.6
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 136	4.3 percentage change	Standard Deviation 3.3
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 88	3.7 percentage change	Standard Deviation 2.4
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	PDLB at Week 72	3.9 percentage change	—
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	End of Study	-5.8 percentage change	Standard Deviation 4.7
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	PDLB at Week 96	4.6 percentage change	Standard Deviation 7.8
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 64	1.3 percentage change	Standard Deviation 5.3
Placebo	Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS	Week 52	0.3 percentage change	Standard Deviation 6.9

Secondary

Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS

PDLB=post-dose liver biopsy

Time frame: Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)

Population: Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 52	-8.3 percentage change	Standard Deviation 36.6
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 16	19.2 percentage change	Standard Deviation 38.5
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 16 + 24 H	16.4 percentage change	Standard Deviation 19.2
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 48	11.8 percentage change	Standard Deviation 27.8
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 28	26.7 percentage change	Standard Deviation 36.1
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	End of Study	41.8 percentage change	Standard Deviation 36.4
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 100	-11.9 percentage change	Standard Deviation 25.2
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 88	38.0 percentage change	Standard Deviation 53.7
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 40	20.6 percentage change	Standard Deviation 27.8
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 64	10.3 percentage change	Standard Deviation 51
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 112	-5.4 percentage change	—
Fazirsiran 25 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 76	18.1 percentage change	Standard Deviation 16.1
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 16	15.6 percentage change	Standard Deviation 41.7
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 16 + 24 H	25.3 percentage change	Standard Deviation 49.7
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 28	27.8 percentage change	Standard Deviation 51.4
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 64	28.5 percentage change	Standard Deviation 38
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 40	30.2 percentage change	Standard Deviation 51.4
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 48	10.8 percentage change	Standard Deviation 68.2
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 52	27.5 percentage change	Standard Deviation 48.8
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 76	40.1 percentage change	Standard Deviation 57.1
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 88	13.1 percentage change	Standard Deviation 1.7
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 96	0.8 percentage change	Standard Deviation 15.9
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 100	-8.6 percentage change	Standard Deviation 15.3
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 112	-5.0 percentage change	Standard Deviation 35.1
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 124	-23.6 percentage change	Standard Deviation 3.9
Fazirsiran 100 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	End of Study	11.5 percentage change	Standard Deviation 26.4
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 52	25.4 percentage change	Standard Deviation 29.4
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 64	10.0 percentage change	Standard Deviation 35.7
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 76	0.3 percentage change	Standard Deviation 31.6
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 88	5.4 percentage change	Standard Deviation 29.3
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Early Termination	-2.9 percentage change	Standard Deviation 4.2
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 96	39.5 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 28	15.8 percentage change	Standard Deviation 36.8
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 16 + 24 H	3.1 percentage change	Standard Deviation 33.1
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 100	25.1 percentage change	Standard Deviation 4
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 112	37.0 percentage change	Standard Deviation 52.4
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	End of Study	25.0 percentage change	Standard Deviation 69.2
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 124	30.2 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 136	23.3 percentage change	—
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 40	10.0 percentage change	Standard Deviation 21.6
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 16	3.4 percentage change	Standard Deviation 44.1
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 48	36.5 percentage change	Standard Deviation 52.2
Fazirsiran 200 mg	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 148	16.3 percentage change	—
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 100	0.4 percentage change	Standard Deviation 31.6
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 16 + 24 H	-16.3 percentage change	Standard Deviation 12.6
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 52	15.5 percentage change	Standard Deviation 36.4
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 72	-60.0 percentage change	—
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	End of Study	26.8 percentage change	Standard Deviation 16.6
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 148	-7.6 percentage change	Standard Deviation 29.7
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 64	-13.3 percentage change	Standard Deviation 28.1
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 76	-1.0 percentage change	Standard Deviation 33.2
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 28	1.3 percentage change	Standard Deviation 37.5
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 160	-13.4 percentage change	Standard Deviation 0.9
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 112	-5.8 percentage change	Standard Deviation 30.8
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 88	-7.6 percentage change	Standard Deviation 21.4
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 40	7.8 percentage change	Standard Deviation 46.4
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 48	-10.9 percentage change	Standard Deviation 29.4
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	PDLB at Week 96	9.2 percentage change	Standard Deviation 1.7
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 124	-5.7 percentage change	Standard Deviation 12.4
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 16	1.0 percentage change	Standard Deviation 28
Placebo	Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS	Week 136	4.4 percentage change	Standard Deviation 25.2

Secondary

Percent Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis

Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96.

Time frame: Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks)

Population: Biopsy Analysis Set: All randomized participants who received at least one dose of study drug and had at least one central read histology biopsy result.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Fazirsiran 25 mg	Percent Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis	-86.36 percentage change	Standard Error 60.305
Fazirsiran 100 mg	Percent Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis	-72.44 percentage change	Standard Error 58.358
Fazirsiran 200 mg	Percent Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis	-101.85 percentage change	Standard Error 47.495
Placebo	Percent Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis	91.35 percentage change	Standard Error 42.75

p-value: 0.024795% CI: [-335.77, -25.64]ANCOVA

p-value: 0.038295% CI: [-317.65, -9.93]ANCOVA

p-value: 0.006495% CI: [-325.25, -61.15]ANCOVA

Secondary

Percent Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis

Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96.

Time frame: Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks)

Population: Biopsy Analysis Set: All randomized participants who received at least one dose of study drug and had at least one central read histology biopsy result.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Fazirsiran 25 mg	Percent Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis	-75.73 percentage change	Standard Error 16.645
Fazirsiran 100 mg	Percent Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis	-87.23 percentage change	Standard Error 17.064
Fazirsiran 200 mg	Percent Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis	-95.71 percentage change	Standard Error 12.824
Placebo	Percent Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis	22.33 percentage change	Standard Error 11.89

p-value: 0.000195% CI: [-140.53, -55.6]ANCOVA

p-value: <0.000195% CI: [-154.81, -64.32]ANCOVA

p-value: <0.000195% CI: [-153.95, -82.12]ANCOVA

Secondary

Percent Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis

Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96.

Time frame: Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks)

Population: Biopsy Analysis Set: All randomized participants who received at least one dose of study drug and had at least one central read histology biopsy result.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Fazirsiran 25 mg	Percent Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis	-86.89 percentage change	Standard Error 29.658
Fazirsiran 100 mg	Percent Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis	-81.61 percentage change	Standard Error 29.503
Fazirsiran 200 mg	Percent Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis	-98.16 percentage change	Standard Error 23.256
Placebo	Percent Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis	42.42 percentage change	Standard Error 21.133

p-value: 0.002195% CI: [-205.52, -53.11]ANCOVA

p-value: 0.003595% CI: [-201.9, -46.15]ANCOVA

p-value: 0.000295% CI: [-205.27, -75.89]ANCOVA

Secondary

Percent Change in Serum Z-AAT Over Time Through EOS

PDLB=post-dose liver biopsy

Time frame: Baseline, Weeks 2, 4, 6, 16, 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks)

Population: Full Analysis Set: All randomized participants who received at least one dose of study drug; participants with an assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Fazirsiran 25 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 112	-91.7 percentage change	—
Fazirsiran 25 mg	Percent Change in Serum Z-AAT Over Time Through EOS	End of Study	-18.0 percentage change	Standard Deviation 2.7
Fazirsiran 25 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 28	-48.2 percentage change	Standard Deviation 20.6
Fazirsiran 25 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 6	-71.9 percentage change	Standard Deviation 14
Fazirsiran 25 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 88	-60.1 percentage change	Standard Deviation 32.6
Fazirsiran 25 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 100	-82.5 percentage change	Standard Deviation 10.1
Fazirsiran 25 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 40	-48.3 percentage change	Standard Deviation 23.4
Fazirsiran 25 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 2	-50.8 percentage change	Standard Deviation 21.9
Fazirsiran 25 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 64	-70.1 percentage change	Standard Deviation 23.5
Fazirsiran 25 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 16	-62.4 percentage change	Standard Deviation 17
Fazirsiran 25 mg	Percent Change in Serum Z-AAT Over Time Through EOS	PDLB at Week 48	-73.9 percentage change	Standard Deviation 16.7
Fazirsiran 25 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 76	-71.8 percentage change	Standard Deviation 19.6
Fazirsiran 25 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 4	-60.0 percentage change	Standard Deviation 24.6
Fazirsiran 25 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 52	-45.9 percentage change	Standard Deviation 24.7
Fazirsiran 100 mg	Percent Change in Serum Z-AAT Over Time Through EOS	PDLB at Week 96	-80.9 percentage change	Standard Deviation 9.1
Fazirsiran 100 mg	Percent Change in Serum Z-AAT Over Time Through EOS	PDLB at Week 48	-89.2 percentage change	Standard Deviation 2.5
Fazirsiran 100 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 88	-77.8 percentage change	Standard Deviation 7.2
Fazirsiran 100 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 52	-73.0 percentage change	Standard Deviation 12.9
Fazirsiran 100 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 4	-82.2 percentage change	Standard Deviation 7.1
Fazirsiran 100 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 64	-77.6 percentage change	Standard Deviation 9.5
Fazirsiran 100 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 76	-75.1 percentage change	Standard Deviation 9
Fazirsiran 100 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 6	-88.4 percentage change	Standard Deviation 5
Fazirsiran 100 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 2	-69.9 percentage change	Standard Deviation 11.4
Fazirsiran 100 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 112	-78.4 percentage change	Standard Deviation 9.9
Fazirsiran 100 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 16	-85.7 percentage change	Standard Deviation 7.6
Fazirsiran 100 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 100	-72.5 percentage change	Standard Deviation 11.2
Fazirsiran 100 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 28	-80.6 percentage change	Standard Deviation 7.9
Fazirsiran 100 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 124	-70.1 percentage change	Standard Deviation 15.2
Fazirsiran 100 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 40	-76.5 percentage change	Standard Deviation 10.5
Fazirsiran 100 mg	Percent Change in Serum Z-AAT Over Time Through EOS	End of Study	-53.8 percentage change	Standard Deviation 6.6
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 16	-91.9 percentage change	Standard Deviation 5.8
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 2	-85.5 percentage change	Standard Deviation 4.8
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 4	-91.8 percentage change	Standard Deviation 2.5
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 6	-95.5 percentage change	Standard Deviation 1.9
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 28	-87.6 percentage change	Standard Deviation 10.4
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 40	-81.3 percentage change	Standard Deviation 18.8
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	PDLB at Week 48	-93.9 percentage change	Standard Deviation 5
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 52	-82.1 percentage change	Standard Deviation 20.5
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 64	-92.2 percentage change	Standard Deviation 5.7
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 76	-88.8 percentage change	Standard Deviation 10.1
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 88	-90.3 percentage change	Standard Deviation 6.3
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	PDLB at Week 96	-95.6 percentage change	—
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 100	-93.8 percentage change	Standard Deviation 0.3
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 112	-91.3 percentage change	Standard Deviation 3.5
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 124	-90.1 percentage change	—
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 136	-90.3 percentage change	—
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Week 148	-89.1 percentage change	—
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	Early Termination	-91.7 percentage change	Standard Deviation 8.5
Fazirsiran 200 mg	Percent Change in Serum Z-AAT Over Time Through EOS	End of Study	-23.4 percentage change	Standard Deviation 0.1
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	PDLB at Week 96	-11.7 percentage change	Standard Deviation 4.2
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	Week 28	0.1 percentage change	Standard Deviation 11.2
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	Week 16	4.3 percentage change	Standard Deviation 12.2
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	Week 148	3.1 percentage change	Standard Deviation 4.1
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	Week 100	-21.3 percentage change	Standard Deviation 29.6
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	Week 112	-8.4 percentage change	Standard Deviation 9.2
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	Week 6	3.4 percentage change	Standard Deviation 11.4
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	Week 160	2.4 percentage change	Standard Deviation 2.9
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	End of Study	9.1 percentage change	Standard Deviation 12.4
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	Week 124	-9.9 percentage change	Standard Deviation 9.1
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	PDLB at Week 72	-2.4 percentage change	—
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	Week 64	2.1 percentage change	Standard Deviation 12.3
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	Week 4	0.5 percentage change	Standard Deviation 8.7
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	Week 76	-2.4 percentage change	Standard Deviation 9.3
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	Week 52	-5.3 percentage change	Standard Deviation 14.9
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	PDLB at Week 48	8.7 percentage change	Standard Deviation 19
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	Week 136	-3.2 percentage change	Standard Deviation 8.8
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	Week 88	0.5 percentage change	Standard Deviation 11.4
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	Week 40	0.3 percentage change	Standard Deviation 9.2
Placebo	Percent Change in Serum Z-AAT Over Time Through EOS	Week 2	10.0 percentage change	Standard Deviation 23.8

Secondary

Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase

Time frame: Fazirsiran participants without fibrosis: Pre-dose, 1 hour, 2 hour, 24 hours post-dose on Day 1 (+/- 1 day). Fazirsiran participants with fibrosis: Pre-dose, 1 hour, 2 hours, 24 hours post-dose on Day 1 and Week 16 (+/- 1 day).

Population: PK Population: all Full Analysis Set participants who have at least 1 measurable plasma concentration data; participants with an assessment at given time point. Data not collected Week 16 for participants with no fibrosis per protocol.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Fazirsiran 25 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 2h	35.0 ng/mL	Geometric Coefficient of Variation 83
Fazirsiran 25 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 1 hour (h)	29.9 ng/mL	Geometric Coefficient of Variation 75.6
Fazirsiran 25 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Week 16, Pre-Dose	0 ng/mL	Geometric Coefficient of Variation 0
Fazirsiran 25 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, Pre-Dose	0 ng/mL	Geometric Coefficient of Variation 0
Fazirsiran 25 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 24h	9.92 ng/mL	Geometric Coefficient of Variation 99.6
Fazirsiran 100 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 24h	6.33 ng/mL	Geometric Coefficient of Variation 176
Fazirsiran 100 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, Pre-Dose	0 ng/mL	Geometric Coefficient of Variation 0
Fazirsiran 100 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 1 hour (h)	50.6 ng/mL	Geometric Coefficient of Variation 66.8
Fazirsiran 100 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 2h	60.7 ng/mL	Geometric Coefficient of Variation 72.5
Fazirsiran 100 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Week 16, Pre-Dose	0 ng/mL	Geometric Coefficient of Variation 0
Fazirsiran 100 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Week 16, 1h	38.1 ng/mL	Geometric Coefficient of Variation 75.3
Fazirsiran 100 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Week 16, 2h	45.1 ng/mL	Geometric Coefficient of Variation 70.1
Fazirsiran 100 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Week 16, 24h	3.64 ng/mL	Geometric Coefficient of Variation 123
Fazirsiran 200 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, Pre-Dose	0 ng/mL	Geometric Coefficient of Variation 0
Fazirsiran 200 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 2h	208.0 ng/mL	Geometric Coefficient of Variation 11.6
Fazirsiran 200 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 24h	69.0 ng/mL	Geometric Coefficient of Variation 88.4
Fazirsiran 200 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 1 hour (h)	190.0 ng/mL	Geometric Coefficient of Variation 17.9
Fazirsiran 200 mg	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Week 16, Pre-Dose	0 ng/mL	Geometric Coefficient of Variation 0
Placebo	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Week 16, 2h	45.1 ng/mL	Geometric Coefficient of Variation 70.1
Placebo	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 2h	199.0 ng/mL	Geometric Coefficient of Variation 32.2
Placebo	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, Pre-Dose	0 ng/mL	Geometric Coefficient of Variation 0
Placebo	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 24h	26.6 ng/mL	Geometric Coefficient of Variation 59.1
Placebo	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Week 16, Pre-Dose	0 ng/mL	Geometric Coefficient of Variation 0
Placebo	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Week 16, 1h	38.1 ng/mL	Geometric Coefficient of Variation 75.3
Placebo	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Week 16, 24h	3.64 ng/mL	Geometric Coefficient of Variation 123
Placebo	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 1 hour (h)	173.0 ng/mL	Geometric Coefficient of Variation 25.7
Fazirsiran 200 mg: Participants With No Fibrosis	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 2h	537.0 ng/mL	Geometric Coefficient of Variation 81.9
Fazirsiran 200 mg: Participants With No Fibrosis	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 24h	11.7 ng/mL	Geometric Coefficient of Variation 17100
Fazirsiran 200 mg: Participants With No Fibrosis	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Week 16, Pre-Dose	0 ng/mL	Geometric Coefficient of Variation 0
Fazirsiran 200 mg: Participants With No Fibrosis	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, Pre-Dose	0 ng/mL	Geometric Coefficient of Variation 0
Fazirsiran 200 mg: Participants With No Fibrosis	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 1 hour (h)	495.0 ng/mL	Geometric Coefficient of Variation 71.8
Fazirsiran 200 mg: Participants With Fibrosis	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 1 hour (h)	356.0 ng/mL	Geometric Coefficient of Variation 75.9
Fazirsiran 200 mg: Participants With Fibrosis	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 24h	27.7 ng/mL	Geometric Coefficient of Variation 612
Fazirsiran 200 mg: Participants With Fibrosis	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, 2h	471.0 ng/mL	Geometric Coefficient of Variation 56.5
Fazirsiran 200 mg: Participants With Fibrosis	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Week 16, 2h	487.0 ng/mL	Geometric Coefficient of Variation 62.5
Fazirsiran 200 mg: Participants With Fibrosis	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Day 1, Pre-Dose	0 ng/mL	Geometric Coefficient of Variation 0
Fazirsiran 200 mg: Participants With Fibrosis	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Week 16, Pre-Dose	0 ng/mL	Geometric Coefficient of Variation 0
Fazirsiran 200 mg: Participants With Fibrosis	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Week 16, 24h	104.0 ng/mL	Geometric Coefficient of Variation 26.2
Fazirsiran 200 mg: Participants With Fibrosis	Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase	Week 16, 1h	396.0 ng/mL	Geometric Coefficient of Variation 64.9

Source: ClinicalTrials.gov · Data processed: Feb 7, 2026

Safety, Tolerability and Pharmacodynamic Effect of Fazirsiran (TAK-999, ARO-AAT)

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16

Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS)

Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS

Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS

Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS

Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS

Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS

Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS

Absolute Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis

Absolute Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis

Absolute Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis

Absolute Change in Serum Z-AAT Over Time Through EOS

Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase

Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis

Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS

Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS

Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS

Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS

Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS

Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS

Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS

Percent Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis

Percent Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis

Percent Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis

Percent Change in Serum Z-AAT Over Time Through EOS

Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase