Mixed Dyslipidemia
Conditions
Brief summary
The purpose of AROANG3-2001 is to evaluate the efficacy and safety of ARO-ANG3 in participants with mixed dyslipidemia. Participants will initially receive 2 subcutaneous injections of ARO-ANG3 or placebo. Participants who complete the double-blind treatment period may opt to continue in an open-label extension during which they will receive up to 8 doses of ARO-ANG3.
Interventions
DRUGARO-ANG3
ARO-ANG3 Injection
DRUGPlacebo
Sterile Normal Saline (0.9% NaCl)
Sponsors
Arrowhead Pharmaceuticals
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Based on medical history, evidence of triglycerides (TG) ≥ 150 mg/dL but ≤ 499 mg/dL * Fasting levels at Screening of LDL-C ≥ 70 mg/dL OR non-HDL-C ≥ 100 mg/dL after at least 4 weeks of stable diet and stable optimal statin therapy * Mean fasting TG ≥ 150 mg/dL and ≤ 499 mg/dL during Screening collected at two separate and consecutive visits and at least 7 days apart and not more than 17 days apart * Willing to follow diet counseling and maintain a stable diet per Investigator judgment based on local standard of care * Participants of childbearing potential must agree to use highly-effective contraception during the study and for at least 24 weeks from last dose of study medication * Women of childbearing potential must have a negative pregnancy test and cannot be breastfeeding * Women of childbearing potential on hormonal contraceptives must be stable on the medication for ≥ 2 menstrual cycles prior to Day 1 * Men must not donate sperm during the study and for at least 24 weeks following the last dose of study medication * Able and willing to provide written informed consent and to comply with study requirements
Exclusion criteria
* Current use or use within 365 days from Day 1 of any hepatocyte targeted siRNA or antisense oligonucleotide molecule * Active pancreatitis within 12 weeks prior to Day 1 * Any planned bariatric surgery or similar procedures to induce weight loss from consent to end of study * Acute coronary syndrome event within 24 weeks of Day 1 * Major surgery within 12 weeks of Day 1 or planned surgery during the study * Planned coronary intervention (e.g., stent placement or heart bypass) during the study * Uncontrolled hypertension * Human immunodeficiency virus (HIV) infection, seropositive for Hepatitis B (HBV), seropositive for Hepatitis C (HCV) * Uncontrolled hypothyroidism or hyperthyroidism * Hemorrhagic stroke within 24 weeks of Day 1 * History of bleeding diathesis or coagulopathy * Current diagnosis of nephrotic syndrome * Systemic use of corticosteroids or anabolic steroids within 4 weeks prior to Day 1 or planned use during the study * Malignancy within the last 2 years prior to date of consent requiring systemic treatment (some exceptions apply) Note: additional inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in Fasting TG at Week 24 | Baseline, Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Fasting TG Over Time | Baseline, up to Week 36 (double-blind treatment period) | — |
| Percent Change From Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24 | Baseline, Week 24 | — |
| Percent Change From Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24 | Baseline, Week 24 | — |
| Percent Change From Baseline in Fasting Total ApoB Over Time | Baseline, up to Week 36 (double-blind treatment period) | — |
| Percent Change From Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24 | Baseline, Week 24 | — |
| Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Baseline, up to Week 36 (double-blind treatment period) | — |
| Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24 | Baseline, Week 24 | — |
| Percent Change From Baseline in ANGPTL3 Over Time | Baseline, up to Week 36 (double-blind treatment period) | — |
| Percent Change From Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24 | Baseline, Week 24 | — |
| Percent Change From Baseline in Fasting HDL-C Over Time | Baseline, up to Week 36 (double-blind treatment period) | — |
| Percent Change From Baseline in Fasting Non-HDL-C Over Time | Baseline, up to Week 36 (double-blind treatment period) | — |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24 | From first dose of IP up to Week 24 | TEAEs are adverse events (AEs) that occur following IP administration or a pre-existing condition exacerbated following IP administration. An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and 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; or is a medically important event or reaction. |
| Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | up to Week 36 (double-blind treatment period) | Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. TEAEs=AEs with onset after administration of the study drug, or when a pre-existing medical condition increases in severity or frequency after study drug administration. Serious adverse event (SAE)= 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. |
| Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | From first dose of study drug in the OLE up to Month 24 (open-label extension) | Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. TEAEs=AEs with onset after administration of the study drug, or when a pre-existing medical condition increases in severity or frequency after study drug administration. Serious adverse event (SAE)= 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. |
| Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Baseline, OLE Baseline, Months 1-24 (open-label extension) | — |
| Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Baseline, OLE Baseline, Months 1-24 (open-label extension) | — |
| Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Baseline, OLE Baseline, Months 1-24 (open-label extension) | — |
| Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Baseline, OLE Baseline, Months 1-24 (open-label extension) | — |
| Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Baseline, OLE Baseline, Months 1-24 (open-label extension) | — |
| Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Baseline, OLE Baseline, Months 1-24 (open-label extension) | — |
| Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Baseline, Day 1: pre-dose, 15 minutes, 1, 3, 6 hours post-dose; Day 2: 24 hours post-dose; Week 12: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose (double-blind treatment period) | — |
Countries
Australia, Canada, New Zealand, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo calculated volume to match active treatment by subcutaneous (sc) injection at Day 1 and Week 12 during the double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period. | 51 |
| ARO-ANG3 50 mg ARO-ANG3 50 mg by sc injection at Day 1 and Week 12 during the double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period. | 51 |
| ARO-ANG3 100 mg ARO-ANG3 100 mg by sc injection at Day 1 and Week 12 during the double-blind treatment period.Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period. | 51 |
| ARO-ANG3 200 mg ARO-ANG3 200 mg by sc injection at Day 1 and Week 12 during the double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period. | 51 |
| Total | 204 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Double-Blind (DB) Treatment Period | Death | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind (DB) Treatment Period | Lost to Follow-up | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind (DB) Treatment Period | Other, Not Specified | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind (DB) Treatment Period | Withdrawal by Subject | 1 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Open-Label Extension (OLE) Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 1 | 1 |
| Open-Label Extension (OLE) Period | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Open-Label Extension (OLE) Period | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
| Open-Label Extension (OLE) Period | Other, Not Specified | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 |
| Open-Label Extension (OLE) Period | Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 7 | 18 | 7 | 19 | 4 | 19 |
| Open-Label Extension (OLE) Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 2 | 2 | 3 |
Baseline characteristics
| Characteristic | Placebo | ARO-ANG3 50 mg | ARO-ANG3 100 mg | ARO-ANG3 200 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 60.2 years STANDARD_DEVIATION 11.3 | 60.4 years STANDARD_DEVIATION 12.68 | 60.0 years STANDARD_DEVIATION 9.89 | 61.5 years STANDARD_DEVIATION 12.53 | 60.5 years STANDARD_DEVIATION 11.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 12 Participants | 18 Participants | 13 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 39 Participants | 33 Participants | 38 Participants | 149 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Mean Triglycerides (TG) at Baseline | 235.15 mg/dL STANDARD_DEVIATION 86.117 | 242.47 mg/dL STANDARD_DEVIATION 79.864 | 246.71 mg/dL STANDARD_DEVIATION 97.996 | 259.97 mg/dL STANDARD_DEVIATION 93.32 | 246.08 mg/dL STANDARD_DEVIATION 89.386 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 48 Participants | 49 Participants | 49 Participants | 49 Participants | 195 Participants |
| Sex: Female, Male Female | 24 Participants | 25 Participants | 22 Participants | 24 Participants | 95 Participants |
| Sex: Female, Male Male | 27 Participants | 26 Participants | 29 Participants | 27 Participants | 109 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 | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 51 | 0 / 50 | 0 / 51 | 0 / 52 | 0 / 13 | 0 / 36 | 0 / 14 | 1 / 39 | 0 / 13 | 0 / 41 |
| other Total, other adverse events | 41 / 51 | 38 / 50 | 41 / 51 | 42 / 52 | 10 / 13 | 31 / 36 | 14 / 14 | 34 / 39 | 11 / 13 | 34 / 41 |
| serious Total, serious adverse events | 4 / 51 | 5 / 50 | 0 / 51 | 1 / 52 | 3 / 13 | 4 / 36 | 2 / 14 | 5 / 39 | 2 / 13 | 5 / 41 |
Outcome results
Primary
Percent Change From Baseline in Fasting TG at Week 24
Time frame: Baseline, Week 24
Population: Full Analysis Set: All randomized participants who received at least 1 dose of investigational product (IP) during the study period, analyzed according to the treatment assigned at randomization.Observed cases.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting TG at Week 24 | 7.55 percentage change | Standard Error 3.774 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG at Week 24 | -43.67 percentage change | Standard Error 3.77 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG at Week 24 | -49.01 percentage change | Standard Error 3.777 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG at Week 24 | -55.57 percentage change | Standard Error 3.726 |
p-value: <0.000195% CI: [-61.73, -40.7]Mixed Models Repeated Measures (MMRM)
p-value: <0.0001Holm method
p-value: <0.000195% CI: [-67.09, -46.04]Mixed Models Repeated Measures (MMRM)
p-value: <0.0001Holm method
p-value: <0.000195% CI: [-73.56, -52.66]Mixed Model with Repeated Measures
p-value: <0.0001Holm method
Secondary
Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period
Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. TEAEs=AEs with onset after administration of the study drug, or when a pre-existing medical condition increases in severity or frequency after study drug administration. Serious adverse event (SAE)= 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.
Time frame: From first dose of study drug in the OLE up to Month 24 (open-label extension)
Population: Safety Analysis Set: All participants who received at least 1 dose of IP during the study period, analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | TEAEs leading to study drug discontinuation | 0 Participants |
| Placebo | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Treatment-related TEAEs | 2 Participants |
| Placebo | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | All Treatment-Emergent Adverse Events (TEAEs) | 10 Participants |
| Placebo | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Deaths | 0 Participants |
| Placebo | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Serious TEAEs | 3 Participants |
| ARO-ANG3 50 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Treatment-related TEAEs | 8 Participants |
| ARO-ANG3 50 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | TEAEs leading to study drug discontinuation | 0 Participants |
| ARO-ANG3 50 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | All Treatment-Emergent Adverse Events (TEAEs) | 27 Participants |
| ARO-ANG3 50 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Deaths | 0 Participants |
| ARO-ANG3 50 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Serious TEAEs | 4 Participants |
| ARO-ANG3 100 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Treatment-related TEAEs | 4 Participants |
| ARO-ANG3 100 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | TEAEs leading to study drug discontinuation | 1 Participants |
| ARO-ANG3 100 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Deaths | 0 Participants |
| ARO-ANG3 100 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Serious TEAEs | 2 Participants |
| ARO-ANG3 100 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | All Treatment-Emergent Adverse Events (TEAEs) | 13 Participants |
| ARO-ANG3 200 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Serious TEAEs | 5 Participants |
| ARO-ANG3 200 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | All Treatment-Emergent Adverse Events (TEAEs) | 30 Participants |
| ARO-ANG3 200 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Treatment-related TEAEs | 6 Participants |
| ARO-ANG3 200 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | TEAEs leading to study drug discontinuation | 2 Participants |
| ARO-ANG3 200 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Deaths | 1 Participants |
| Placebo/ARO-ANG3 200 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | TEAEs leading to study drug discontinuation | 1 Participants |
| Placebo/ARO-ANG3 200 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | All Treatment-Emergent Adverse Events (TEAEs) | 10 Participants |
| Placebo/ARO-ANG3 200 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Deaths | 0 Participants |
| Placebo/ARO-ANG3 200 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Treatment-related TEAEs | 0 Participants |
| Placebo/ARO-ANG3 200 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Serious TEAEs | 2 Participants |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | All Treatment-Emergent Adverse Events (TEAEs) | 31 Participants |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | TEAEs leading to study drug discontinuation | 1 Participants |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Treatment-related TEAEs | 6 Participants |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Deaths | 0 Participants |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period | Serious TEAEs | 5 Participants |
Secondary
Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period
Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. TEAEs=AEs with onset after administration of the study drug, or when a pre-existing medical condition increases in severity or frequency after study drug administration. Serious adverse event (SAE)= 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.
Time frame: up to Week 36 (double-blind treatment period)
Population: Safety Analysis Set: All participants who received at least 1 dose of IP during the study period, analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | All Treatment-Emergent Adverse Events (TEAEs) | 35 Participants |
| Placebo | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | Treatment-related TEAEs | 8 Participants |
| Placebo | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | Serious TEAEs | 4 Participants |
| Placebo | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | TEAEs leading to study drug discontinuation | 2 Participants |
| Placebo | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | Deaths | 1 Participants |
| Placebo | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | Local Injection Site Reactions (LISR) | 1 Participants |
| ARO-ANG3 50 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | Local Injection Site Reactions (LISR) | 0 Participants |
| ARO-ANG3 50 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | TEAEs leading to study drug discontinuation | 0 Participants |
| ARO-ANG3 50 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | All Treatment-Emergent Adverse Events (TEAEs) | 40 Participants |
| ARO-ANG3 50 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | Serious TEAEs | 5 Participants |
| ARO-ANG3 50 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | Treatment-related TEAEs | 12 Participants |
| ARO-ANG3 50 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | Deaths | 0 Participants |
| ARO-ANG3 100 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | Treatment-related TEAEs | 8 Participants |
| ARO-ANG3 100 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | Serious TEAEs | 0 Participants |
| ARO-ANG3 100 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | TEAEs leading to study drug discontinuation | 1 Participants |
| ARO-ANG3 100 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | Local Injection Site Reactions (LISR) | 3 Participants |
| ARO-ANG3 100 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | Deaths | 0 Participants |
| ARO-ANG3 100 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | All Treatment-Emergent Adverse Events (TEAEs) | 34 Participants |
| ARO-ANG3 200 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | Deaths | 0 Participants |
| ARO-ANG3 200 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | Local Injection Site Reactions (LISR) | 2 Participants |
| ARO-ANG3 200 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | Treatment-related TEAEs | 12 Participants |
| ARO-ANG3 200 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | TEAEs leading to study drug discontinuation | 0 Participants |
| ARO-ANG3 200 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | All Treatment-Emergent Adverse Events (TEAEs) | 42 Participants |
| ARO-ANG3 200 mg | Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period | Serious TEAEs | 1 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24
TEAEs are adverse events (AEs) that occur following IP administration or a pre-existing condition exacerbated following IP administration. An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and 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; or is a medically important event or reaction.
Time frame: From first dose of IP up to Week 24
Population: Safety Analysis Set: All participants who received at least 1 dose of IP during the study period, analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24 | All TEAEs (Including Serious) | 30 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24 | Serious TEAEs | 3 Participants |
| ARO-ANG3 50 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24 | Serious TEAEs | 3 Participants |
| ARO-ANG3 50 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24 | All TEAEs (Including Serious) | 37 Participants |
| ARO-ANG3 100 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24 | All TEAEs (Including Serious) | 29 Participants |
| ARO-ANG3 100 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24 | Serious TEAEs | 0 Participants |
| ARO-ANG3 200 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24 | All TEAEs (Including Serious) | 39 Participants |
| ARO-ANG3 200 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24 | Serious TEAEs | 1 Participants |
Secondary
Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24
Time frame: Baseline, Week 24
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization.Observed cases.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24 | 1.24 percentage change | Standard Error 2.801 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24 | -53.02 percentage change | Standard Error 2.829 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24 | -68.52 percentage change | Standard Error 2.807 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24 | -72.45 percentage change | Standard Error 2.761 |
p-value: <0.000195% CI: [-62.11, -46.4]mixed Models Repeated Measures
p-value: <0.000195% CI: [-77.58, -61.95]Mixed Models Repeated Measures
p-value: <0.000195% CI: [-81.44, -65.93]Mixed Models Repeated Measures
Secondary
Percent Change From Baseline in ANGPTL3 Over Time
Time frame: Baseline, up to Week 36 (double-blind treatment period)
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time | Week 4 | 5.54 percentage change | Standard Error 2.353 |
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time | Week 8 | 2.97 percentage change | Standard Error 3.023 |
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time | Week 12 | 7.38 percentage change | Standard Error 3.599 |
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time | Week 16 | 8.48 percentage change | Standard Error 2.379 |
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time | Week 20 | 4.35 percentage change | Standard Error 2.338 |
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time | Week 24 | 1.24 percentage change | Standard Error 2.801 |
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time | Week 28 | 5.18 percentage change | Standard Error 2.879 |
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time | Week 36 | 3.73 percentage change | Standard Error 3.11 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 24 | -53.02 percentage change | Standard Error 2.829 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 20 | -60.50 percentage change | Standard Error 2.36 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 8 | -56.09 percentage change | Standard Error 3.074 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 36 | -41.70 percentage change | Standard Error 3.158 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 28 | -49.57 percentage change | Standard Error 2.92 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 16 | -63.73 percentage change | Standard Error 2.4 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 12 | -47.72 percentage change | Standard Error 3.635 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 4 | -62.11 percentage change | Standard Error 2.388 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 28 | -61.43 percentage change | Standard Error 2.921 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 12 | -63.17 percentage change | Standard Error 3.608 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 16 | -75.61 percentage change | Standard Error 2.379 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 20 | -73.10 percentage change | Standard Error 2.347 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 24 | -68.52 percentage change | Standard Error 2.807 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 36 | -53.41 percentage change | Standard Error 3.155 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 4 | -75.25 percentage change | Standard Error 2.401 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 8 | -69.01 percentage change | Standard Error 3.066 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 12 | -66.62 percentage change | Standard Error 3.542 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 16 | -80.52 percentage change | Standard Error 2.345 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 8 | -73.47 percentage change | Standard Error 3.045 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 4 | -79.15 percentage change | Standard Error 2.365 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 20 | -76.25 percentage change | Standard Error 2.299 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 36 | -59.85 percentage change | Standard Error 3.066 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 28 | -68.19 percentage change | Standard Error 2.852 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time | Week 24 | -72.45 percentage change | Standard Error 2.761 |
Comparison: Week 4p-value: <0.000195% CI: [-74.26, -61.04]Mixed Model Repeated Measures (MMRM)
Comparison: Week 4p-value: <0.000195% CI: [-87.42, -74.17]Mixed Model Repeated Measures (MMRM)
Comparison: Week 4p-value: <0.000195% CI: [-91.27, -78.12]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: <0.000195% CI: [-67.57, -50.57]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: <0.000195% CI: [-80.47, -63.5]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: <0.000195% CI: [-84.9, -67.99]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: <0.000195% CI: [-65.18, -45.01]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: <0.000195% CI: [-80.6, -60.51]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: <0.000195% CI: [-83.95, -64.04]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: <0.000195% CI: [-78.88, -65.56]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: <0.000195% CI: [-90.72, -77.46]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: <0.000195% CI: [-95.59, -82.42]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: <0.000195% CI: [-71.4, -58.31]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: <0.000195% CI: [-83.98, -70.93]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: <0.000195% CI: [-87.06, -74.14]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: <0.000195% CI: [-62.11, -46.4]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: <0.000195% CI: [-77.58, -61.95]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: <0.000195% CI: [-81.44, -65.93]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: <0.000195% CI: [-62.84, -46.67]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: <0.000195% CI: [-74.69, -58.52]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: <0.000195% CI: [-81.36, -65.38]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: <0.000195% CI: [-54.17, -36.69]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: <0.000195% CI: [-65.88, -48.41]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: <0.000195% CI: [-72.19, -54.97]Mixed Model Repeated Measures (MMRM)
Secondary
Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period
Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -49.22 percentage change | Standard Error 5.28 |
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -43.36 percentage change | Standard Error 5.072 |
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -53.85 percentage change | Standard Error 3.393 |
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -44.08 percentage change | Standard Error 10.028 |
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -40.12 percentage change | Standard Error 5.814 |
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -36.82 percentage change | Standard Error 9.076 |
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -53.01 percentage change | Standard Error 3.998 |
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -59.55 percentage change | Standard Error 3.49 |
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | 3.41 percentage change | Standard Error 5.372 |
| Placebo | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -55.48 percentage change | Standard Error 5.056 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -60.01 percentage change | Standard Error 3.812 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -41.57 percentage change | Standard Error 4.417 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -65.83 percentage change | Standard Error 2.836 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -48.56 percentage change | Standard Error 6.842 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -54.18 percentage change | Standard Error 4.076 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -55.20 percentage change | Standard Error 4.666 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -52.97 percentage change | Standard Error 4.56 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -39.57 percentage change | Standard Error 5.638 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -43.45 percentage change | Standard Error 5.176 |
| ARO-ANG3 50 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -50.18 percentage change | Standard Error 6.57 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -77.02 percentage change | Standard Error 2.699 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -61.65 percentage change | Standard Error 4.51 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -71.03 percentage change | Standard Error 4.37 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -67.23 percentage change | Standard Error 4.07 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -65.71 percentage change | Standard Error 4.877 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | 4.47 percentage change | Standard Error 7.595 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -63.26 percentage change | Standard Error 4.176 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -48.46 percentage change | Standard Error 14.321 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -65.80 percentage change | Standard Error 4.669 |
| ARO-ANG3 100 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -67.75 percentage change | Standard Error 4.771 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -65.28 percentage change | Standard Error 6.196 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -56.81 percentage change | Standard Error 3.166 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -62.95 percentage change | Standard Error 4.439 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -65.97 percentage change | Standard Error 3.28 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -68.85 percentage change | Standard Error 2.867 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -65.54 percentage change | Standard Error 3.02 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -69.32 percentage change | Standard Error 3.691 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -71.21 percentage change | Standard Error 2.367 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -64.68 percentage change | Standard Error 3.414 |
| ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -76.03 percentage change | Standard Error 1.982 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -74.62 percentage change | Standard Error 3.753 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -64.79 percentage change | Standard Error 5.478 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -69.38 percentage change | Standard Error 3.736 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -63.23 percentage change | Standard Error 5.801 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -64.57 percentage change | Standard Error 3.909 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | 0.79 percentage change | Standard Error 4.664 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -61.38 percentage change | Standard Error 4.943 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -61.52 percentage change | Standard Error 3.012 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -58.10 percentage change | Standard Error 4.837 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -70.19 percentage change | Standard Error 3.928 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -59.24 percentage change | Standard Error 3.551 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -62.00 percentage change | Standard Error 4.122 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -74.59 percentage change | Standard Error 2.775 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -77.96 percentage change | Standard Error 2.273 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -63.89 percentage change | Standard Error 4.009 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -67.04 percentage change | Standard Error 3.743 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -68.91 percentage change | Standard Error 3.31 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -55.31 percentage change | Standard Error 4.725 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -55.73 percentage change | Standard Error 5.734 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -55.43 percentage change | Standard Error 4.784 |
Secondary
Percent Change From Baseline in Fasting HDL-C Over Time
Time frame: Baseline, up to Week 36 (double-blind treatment period)
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time | Week 4 | -0.3 percentage change | Standard Error 2.59 |
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time | Week 8 | 0.4 percentage change | Standard Error 2.67 |
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time | Week 12 | 2.0 percentage change | Standard Error 3.1 |
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time | Week 16 | 2.1 percentage change | Standard Error 2.99 |
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time | Week 20 | 3.4 percentage change | Standard Error 2.89 |
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time | Week 24 | 3.1 percentage change | Standard Error 2.91 |
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time | Week 28 | 3.0 percentage change | Standard Error 2.78 |
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time | Week 36 | 6.4 percentage change | Standard Error 2.78 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 24 | -9.0 percentage change | Standard Error 2.94 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 20 | -11.3 percentage change | Standard Error 2.92 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 8 | -14.5 percentage change | Standard Error 2.71 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 36 | -1.4 percentage change | Standard Error 2.82 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 28 | -5.5 percentage change | Standard Error 2.82 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 16 | -15.8 percentage change | Standard Error 3.02 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 12 | -7.0 percentage change | Standard Error 3.11 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 4 | -13.9 percentage change | Standard Error 2.63 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 28 | -14.7 percentage change | Standard Error 2.87 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 12 | -18.7 percentage change | Standard Error 3.14 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 16 | -28.5 percentage change | Standard Error 3.04 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 20 | -25.1 percentage change | Standard Error 2.94 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 24 | -18.5 percentage change | Standard Error 2.96 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 36 | -13.7 percentage change | Standard Error 2.86 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 4 | -25.5 percentage change | Standard Error 2.68 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 8 | -25.0 percentage change | Standard Error 2.74 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 12 | -18.2 percentage change | Standard Error 3.05 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 16 | -30.2 percentage change | Standard Error 2.96 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 8 | -25.8 percentage change | Standard Error 2.69 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 4 | -24.8 percentage change | Standard Error 2.61 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 20 | -27.1 percentage change | Standard Error 2.86 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 36 | -9.4 percentage change | Standard Error 2.75 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 28 | -18.6 percentage change | Standard Error 2.77 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time | Week 24 | -21.5 percentage change | Standard Error 2.89 |
Comparison: Week 4p-value: 0.000395% CI: [-20.9, -6.4]Mixed Model Repeated Measures (MMRM)
Comparison: Week 4p-value: <0.000195% CI: [-32.6, -17.9]Mixed Model Repeated Measures (MMRM)
Comparison: Week 4p-value: <0.000195% CI: [-31.8, -17.3]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: 0.000195% CI: [-22.4, -7.5]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: <0.000195% CI: [-33, -17.9]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: <0.000195% CI: [-33.7, -18.7]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: 0.042995% CI: [-17.6, -0.3]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: <0.000195% CI: [-29.4, -12]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: <0.000195% CI: [-28.7, -11.6]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: <0.000195% CI: [-26.2, -9.5]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: <0.000195% CI: [-39, -22.2]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: <0.000195% CI: [-40.5, -24]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: 0.000595% CI: [-22.7, -6.5]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: <0.000195% CI: [-36.6, -20.3]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: <0.000195% CI: [-38.4, -22.4]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: 0.003995% CI: [-20.2, -3.9]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: <0.000195% CI: [-29.8, -13.4]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: <0.000195% CI: [-32.6, -16.5]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: 0.034395% CI: [-16.2, -0.6]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: <0.000195% CI: [-25.6, -9.8]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: <0.000195% CI: [-29.3, -13.8]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: 0.050195% CI: [-15.6, 0]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: <0.000195% CI: [-27.9, -12.2]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: <0.000195% CI: [-23.5, -8.1]Mixed Model Repeated Measures (MMRM)
Secondary
Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period
Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -8.80 percentage change | Standard Error 5.376 |
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -9.46 percentage change | Standard Error 6.308 |
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -8.97 percentage change | Standard Error 10.168 |
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -3.87 percentage change | Standard Error 6.823 |
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -10.53 percentage change | Standard Error 6.499 |
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -9.01 percentage change | Standard Error 6.448 |
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -10.68 percentage change | Standard Error 8.416 |
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | 13.70 percentage change | Standard Error 6.036 |
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -13.83 percentage change | Standard Error 7.363 |
| Placebo | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -8.26 percentage change | Standard Error 6.279 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -12.31 percentage change | Standard Error 3.791 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | 1.67 percentage change | Standard Error 3.36 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -10.98 percentage change | Standard Error 3.588 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -9.96 percentage change | Standard Error 3.318 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -3.95 percentage change | Standard Error 4.247 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -16.58 percentage change | Standard Error 3.672 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -12.02 percentage change | Standard Error 5.116 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -4.80 percentage change | Standard Error 5.98 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -12.48 percentage change | Standard Error 3.816 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -11.66 percentage change | Standard Error 5.293 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -15.50 percentage change | Standard Error 4.847 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -21.60 percentage change | Standard Error 5.268 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | 7.70 percentage change | Standard Error 5.318 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -21.38 percentage change | Standard Error 6.028 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -19.64 percentage change | Standard Error 4.846 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -26.62 percentage change | Standard Error 4.804 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -22.23 percentage change | Standard Error 5.893 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -22.77 percentage change | Standard Error 4.713 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -20.28 percentage change | Standard Error 15.397 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -19.76 percentage change | Standard Error 5.356 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -29.44 percentage change | Standard Error 3.11 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -28.55 percentage change | Standard Error 3.462 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -28.81 percentage change | Standard Error 3.214 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -27.31 percentage change | Standard Error 4.225 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -26.12 percentage change | Standard Error 3.535 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -12.88 percentage change | Standard Error 3.147 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -26.51 percentage change | Standard Error 3.816 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -26.54 percentage change | Standard Error 3.486 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -22.29 percentage change | Standard Error 3.771 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -24.78 percentage change | Standard Error 3.397 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -14.07 percentage change | Standard Error 5.004 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -12.81 percentage change | Standard Error 5.209 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -13.75 percentage change | Standard Error 6.207 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -5.47 percentage change | Standard Error 5.504 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | 4.80 percentage change | Standard Error 4.562 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -11.86 percentage change | Standard Error 4.787 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -16.01 percentage change | Standard Error 3.759 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -16.68 percentage change | Standard Error 2.024 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -13.48 percentage change | Standard Error 7.252 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -14.33 percentage change | Standard Error 8.371 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -18.32 percentage change | Standard Error 4.314 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -24.10 percentage change | Standard Error 5.009 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -28.27 percentage change | Standard Error 3.705 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -28.24 percentage change | Standard Error 3.362 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -20.43 percentage change | Standard Error 4.082 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -15.04 percentage change | Standard Error 4.116 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -19.78 percentage change | Standard Error 3.504 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -16.39 percentage change | Standard Error 4.648 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -11.26 percentage change | Standard Error 3.771 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -17.82 percentage change | Standard Error 3.788 |
Secondary
Percent Change From Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24
Time frame: Baseline, Week 24
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization.Observed cases.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24 | 3.1 percentage change | Standard Error 2.91 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24 | -9.0 percentage change | Standard Error 2.94 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24 | -18.5 percentage change | Standard Error 2.96 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24 | -21.5 percentage change | Standard Error 2.89 |
p-value: 0.003995% CI: [-20.2, -3.9]Mixed Models Repeated Measures
p-value: <0.000195% CI: [-29.8, -13.4]Mixed Models Repeated Measures
p-value: <0.000195% CI: [-32.6, -16.5]Mixed Models Repeated Measures
Secondary
Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time
Time frame: Baseline, up to Week 36 (double-blind treatment period)
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 4 | 5.1 percentage change | Standard Error 3.95 |
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 8 | 3.7 percentage change | Standard Error 4.78 |
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 12 | 7.7 percentage change | Standard Error 7.31 |
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 16 | 3.6 percentage change | Standard Error 4.51 |
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 20 | 1.8 percentage change | Standard Error 4.26 |
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 24 | 5.0 percentage change | Standard Error 4.53 |
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 28 | 0.2 percentage change | Standard Error 4.67 |
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 36 | 3.1 percentage change | Standard Error 5.75 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 24 | -11.0 percentage change | Standard Error 4.58 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 20 | -12.2 percentage change | Standard Error 4.31 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 8 | -10.1 percentage change | Standard Error 4.85 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 36 | -8.9 percentage change | Standard Error 5.81 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 28 | -9.1 percentage change | Standard Error 4.75 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 16 | -9.5 percentage change | Standard Error 4.56 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 12 | -7.6 percentage change | Standard Error 7.36 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 4 | -8.3 percentage change | Standard Error 4.03 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 28 | -2.4 percentage change | Standard Error 4.74 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 12 | 7.9 percentage change | Standard Error 7.34 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 16 | -7.4 percentage change | Standard Error 4.52 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 20 | -6.9 percentage change | Standard Error 4.28 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 24 | -4.3 percentage change | Standard Error 4.56 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 36 | 3.7 percentage change | Standard Error 5.82 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 4 | -3.4 percentage change | Standard Error 4.02 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 8 | -0.7 percentage change | Standard Error 4.83 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 12 | -12.1 percentage change | Standard Error 7.23 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 16 | -19.5 percentage change | Standard Error 4.48 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 8 | -10.8 percentage change | Standard Error 4.81 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 4 | -13.7 percentage change | Standard Error 3.98 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 20 | -15.3 percentage change | Standard Error 4.22 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 36 | -4.4 percentage change | Standard Error 5.71 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 28 | -11.3 percentage change | Standard Error 4.66 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time | Week 24 | -15.1 percentage change | Standard Error 4.51 |
Comparison: Week 4p-value: 0.019295% CI: [-24.5, -2.2]Mixed Model Repeated Measures (MMRM)
Comparison: Week 4p-value: 0.136295% CI: [-19.6, 2.7]Mixed Model Repeated Measures (MMRM)
Comparison: Week 4p-value: 0.00195% CI: [-29.8, -7.7]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: 0.042895% CI: [-27.3, -0.5]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: 0.512295% CI: [-17.9, 8.9]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: 0.033195% CI: [-27.9, -1.2]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: 0.1495% CI: [-35.8, 5.1]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: 0.985495% CI: [-20.2, 20.6]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: 0.055295% CI: [-40.1, 0.4]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: 0.04395% CI: [-25.7, -0.4]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: 0.087195% CI: [-23.6, 1.6]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: 0.000495% CI: [-35.7, -10.6]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: 0.021995% CI: [-25.9, -2]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: 0.152695% CI: [-20.6, 3.2]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: 0.004995% CI: [-28.9, -5.2]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: 0.013895% CI: [-28.7, -3.3]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: 0.14895% CI: [-22, 3.3]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: 0.001995% CI: [-32.8, -7.5]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: 0.16695% CI: [-22.4, 3.9]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: 0.696495% CI: [-15.7, 10.5]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: 0.083195% CI: [-24.5, 1.5]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: 0.142595% CI: [-28.2, 4.1]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: 0.949495% CI: [-15.6, 16.6]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: 0.353595% CI: [-23.5, 8.4]Mixed Model Repeated Measures (MMRM)
Secondary
Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period
Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | 3.79 percentage change | Standard Error 8.934 |
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | 5.75 percentage change | Standard Error 6.546 |
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -7.17 percentage change | Standard Error 22.117 |
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | 9.29 percentage change | Standard Error 18.925 |
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -9.73 percentage change | Standard Error 8.195 |
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | 8.54 percentage change | Standard Error 17.305 |
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | 6.61 percentage change | Standard Error 8.96 |
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | 16.61 percentage change | Standard Error 13.866 |
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | 6.95 percentage change | Standard Error 14.056 |
| Placebo | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | 16.09 percentage change | Standard Error 11.331 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -4.90 percentage change | Standard Error 5.203 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -7.68 percentage change | Standard Error 4.934 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -10.81 percentage change | Standard Error 5.105 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -2.69 percentage change | Standard Error 5.57 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -2.03 percentage change | Standard Error 6.503 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -2.77 percentage change | Standard Error 6.09 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -7.84 percentage change | Standard Error 6.363 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -5.88 percentage change | Standard Error 5.801 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -6.14 percentage change | Standard Error 5.553 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -10.57 percentage change | Standard Error 6.996 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -2.47 percentage change | Standard Error 7.839 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -4.52 percentage change | Standard Error 7.677 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -1.59 percentage change | Standard Error 8.079 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -10.68 percentage change | Standard Error 5.7 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -3.40 percentage change | Standard Error 7.119 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -7.43 percentage change | Standard Error 5.762 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -4.64 percentage change | Standard Error 9.376 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -12.81 percentage change | Standard Error 7.465 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -12.81 percentage change | Standard Error 9.496 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -6.14 percentage change | Standard Error 6.38 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -5.41 percentage change | Standard Error 11.638 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -13.20 percentage change | Standard Error 7.882 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -0.07 percentage change | Standard Error 7.654 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -13.83 percentage change | Standard Error 5.902 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -4.47 percentage change | Standard Error 8.744 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | 4.59 percentage change | Standard Error 7.053 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -8.25 percentage change | Standard Error 7.573 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -9.92 percentage change | Standard Error 4.137 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | 1.94 percentage change | Standard Error 7.628 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | 7.38 percentage change | Standard Error 12.473 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | 5.82 percentage change | Standard Error 18.362 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | 5.74 percentage change | Standard Error 20.327 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | 3.32 percentage change | Standard Error 20.431 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | 4.05 percentage change | Standard Error 18.896 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | 4.13 percentage change | Standard Error 5.905 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | 6.86 percentage change | Standard Error 21.962 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -9.58 percentage change | Standard Error 14.506 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -15.64 percentage change | Standard Error 7.008 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | 3.50 percentage change | Standard Error 20.049 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | 3.74 percentage change | Standard Error 16.591 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -6.97 percentage change | Standard Error 4.466 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -6.18 percentage change | Standard Error 6.423 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -10.01 percentage change | Standard Error 4.929 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -10.08 percentage change | Standard Error 4.989 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -2.80 percentage change | Standard Error 6.23 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -7.85 percentage change | Standard Error 5.264 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -1.59 percentage change | Standard Error 6.358 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -8.43 percentage change | Standard Error 5.346 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -2.82 percentage change | Standard Error 5.633 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -2.16 percentage change | Standard Error 5.032 |
Secondary
Percent Change From Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24
Time frame: Baseline, Week 24
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization.Observed cases.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24 | 5.0 percentage change | Standard Error 4.53 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24 | -11.0 percentage change | Standard Error 4.58 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24 | -4.3 percentage change | Standard Error 4.56 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24 | -15.1 percentage change | Standard Error 4.51 |
p-value: 0.013895% CI: [-28.7, -3.3]Mixed Models Repeated Measures
p-value: 0.14895% CI: [-22, 3.3]Mixed Models Repated Measures
p-value: 0.001995% CI: [-32.8, -7.5]Mxed Models Repeated Measures
Secondary
Percent Change From Baseline in Fasting Non-HDL-C Over Time
Time frame: Baseline, up to Week 36 (double-blind treatment period)
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 4 | 5.2 percentage change | Standard Error 2.51 |
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 8 | 3.7 percentage change | Standard Error 3.02 |
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 12 | 3.4 percentage change | Standard Error 3.06 |
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 16 | 2.5 percentage change | Standard Error 2.86 |
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 20 | 0.8 percentage change | Standard Error 2.71 |
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 24 | 4.2 percentage change | Standard Error 3.31 |
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 28 | 1.2 percentage change | Standard Error 3 |
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 36 | -1.5 percentage change | Standard Error 3.19 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 24 | -25.1 percentage change | Standard Error 3.31 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 20 | -28.1 percentage change | Standard Error 2.7 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 8 | -24.4 percentage change | Standard Error 3.04 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 36 | -20.2 percentage change | Standard Error 3.21 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 28 | -23.1 percentage change | Standard Error 3.01 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 16 | -26.8 percentage change | Standard Error 2.86 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 12 | -22.8 percentage change | Standard Error 3.04 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 4 | -23.5 percentage change | Standard Error 2.52 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 28 | -22.3 percentage change | Standard Error 3.04 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 12 | -18.4 percentage change | Standard Error 3.04 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 16 | -28.3 percentage change | Standard Error 2.85 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 20 | -26.5 percentage change | Standard Error 2.69 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 24 | -24.6 percentage change | Standard Error 3.31 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 36 | -17.3 percentage change | Standard Error 3.23 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 4 | -25.3 percentage change | Standard Error 2.55 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 8 | -22.8 percentage change | Standard Error 3.04 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 12 | -28.1 percentage change | Standard Error 2.97 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 16 | -37.0 percentage change | Standard Error 2.81 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 8 | -30.3 percentage change | Standard Error 3.02 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 4 | -32.9 percentage change | Standard Error 2.5 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 20 | -34.1 percentage change | Standard Error 2.64 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 36 | -24.1 percentage change | Standard Error 3.14 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 28 | -30.0 percentage change | Standard Error 2.96 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time | Week 24 | -32.2 percentage change | Standard Error 3.26 |
Comparison: Week 4p-value: <0.000195% CI: [-35.7, -21.7]Mixed Model Repeated Measures (MMRM)
Comparison: Week 4p-value: <0.000195% CI: [-37.5, -23.4]Mixed Model Repeated Measures (MMRM)
Comparison: Week 4p-value: <0.000195% CI: [-45.1, -31.2]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: <0.000195% CI: [-36.6, -19.7]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: <0.000195% CI: [-35, -18.1]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: <0.000195% CI: [-42.4, -25.6]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: <0.000195% CI: [-34.6, -17.6]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: <0.000195% CI: [-30.3, -13.3]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: <0.000195% CI: [-39.9, -23.1]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: <0.000195% CI: [-37.3, -21.4]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: <0.000195% CI: [-38.8, -22.9]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: <0.000195% CI: [-47.4, -31.6]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: <0.000195% CI: [-36.4, -21.4]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: <0.000195% CI: [-34.8, -19.7]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: <0.000195% CI: [-42.3, -27.4]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: <0.000195% CI: [-38.5, -20]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: <0.000195% CI: [-37.9, -19.5]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: <0.000195% CI: [-45.5, -27.2]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: <0.000195% CI: [-32.7, -15.9]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: <0.000195% CI: [-31.9, -15.1]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: <0.000195% CI: [-39.5, -22.9]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: <0.000195% CI: [-27.6, -9.7]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: 0.000695% CI: [-24.7, -6.8]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: <0.000195% CI: [-31.4, -13.8]Mixed Model Repeated Measures (MMRM)
Secondary
Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period
Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -14.32 percentage change | Standard Error 6.774 |
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -14.70 percentage change | Standard Error 5.087 |
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -32.24 percentage change | Standard Error 14.568 |
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -13.13 percentage change | Standard Error 14.219 |
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -23.39 percentage change | Standard Error 6.01 |
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -13.02 percentage change | Standard Error 13.661 |
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -14.79 percentage change | Standard Error 6.493 |
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | 6.70 percentage change | Standard Error 13.049 |
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -13.72 percentage change | Standard Error 9.131 |
| Placebo | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -10.42 percentage change | Standard Error 7.33 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -22.99 percentage change | Standard Error 3.544 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -19.95 percentage change | Standard Error 3.532 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -25.54 percentage change | Standard Error 3.73 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -20.71 percentage change | Standard Error 3.77 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -22.11 percentage change | Standard Error 4.372 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -22.82 percentage change | Standard Error 4.267 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -24.01 percentage change | Standard Error 4.257 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -23.26 percentage change | Standard Error 3.579 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -25.07 percentage change | Standard Error 3.492 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -27.52 percentage change | Standard Error 5.126 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -19.61 percentage change | Standard Error 4.659 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -25.34 percentage change | Standard Error 4.315 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -5.02 percentage change | Standard Error 5.171 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -26.53 percentage change | Standard Error 4.347 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -22.32 percentage change | Standard Error 5.34 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -25.80 percentage change | Standard Error 4.039 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -24.42 percentage change | Standard Error 7.159 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -34.23 percentage change | Standard Error 3.783 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -37.23 percentage change | Standard Error 3.633 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -25.66 percentage change | Standard Error 3.442 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -31.53 percentage change | Standard Error 3.04 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -33.90 percentage change | Standard Error 3.422 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -25.23 percentage change | Standard Error 3.912 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -31.95 percentage change | Standard Error 4.492 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -30.46 percentage change | Standard Error 2.642 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -16.02 percentage change | Standard Error 3.824 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -30.48 percentage change | Standard Error 3.626 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -24.38 percentage change | Standard Error 3.392 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -22.97 percentage change | Standard Error 3.462 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -22.98 percentage change | Standard Error 3.151 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -25.86 percentage change | Standard Error 4.405 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -25.19 percentage change | Standard Error 4.215 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -30.83 percentage change | Standard Error 4.832 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -28.60 percentage change | Standard Error 3.545 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -2.53 percentage change | Standard Error 3.75 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -29.09 percentage change | Standard Error 4.005 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -24.24 percentage change | Standard Error 9.558 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -28.66 percentage change | Standard Error 4.59 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -28.43 percentage change | Standard Error 4.168 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -28.13 percentage change | Standard Error 3.93 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -30.08 percentage change | Standard Error 2.731 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -30.82 percentage change | Standard Error 4.407 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -33.41 percentage change | Standard Error 3.158 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -30.35 percentage change | Standard Error 3.013 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -27.84 percentage change | Standard Error 3.414 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -27.73 percentage change | Standard Error 3.387 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -26.68 percentage change | Standard Error 3.107 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -27.88 percentage change | Standard Error 3.495 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -23.12 percentage change | Standard Error 3.116 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -25.75 percentage change | Standard Error 3.735 |
Secondary
Percent Change From Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24
Time frame: Baseline, Week 24
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization.Observed cases.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24 | 4.2 percentage change | Standard Error 3.31 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24 | -25.1 percentage change | Standard Error 3.31 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24 | -24.6 percentage change | Standard Error 3.31 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24 | -32.2 percentage change | Standard Error 3.26 |
p-value: <0.000195% CI: [-38.5, -20]Mixed Models Repeated Measures
p-value: <0.000195% CI: [-37.9, -19.5]Mixed Models Repeated Measures
p-value: <0.000195% CI: [-45.5, -27.2]Mixed Models Repeated Measures
Secondary
Percent Change From Baseline in Fasting TG Over Time
Time frame: Baseline, up to Week 36 (double-blind treatment period)
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting TG Over Time | Week 4 | 7.00 percentage change | Standard Error 3.583 |
| Placebo | Percent Change From Baseline in Fasting TG Over Time | Week 8 | 13.58 percentage change | Standard Error 4.188 |
| Placebo | Percent Change From Baseline in Fasting TG Over Time | Week 12 | 2.17 percentage change | Standard Error 4.305 |
| Placebo | Percent Change From Baseline in Fasting TG Over Time | Week 16 | 17.18 percentage change | Standard Error 6.952 |
| Placebo | Percent Change From Baseline in Fasting TG Over Time | Week 20 | 11.54 percentage change | Standard Error 5.93 |
| Placebo | Percent Change From Baseline in Fasting TG Over Time | Week 24 | 7.55 percentage change | Standard Error 3.774 |
| Placebo | Percent Change From Baseline in Fasting TG Over Time | Week 28 | 7.24 percentage change | Standard Error 3.95 |
| Placebo | Percent Change From Baseline in Fasting TG Over Time | Week 36 | -0.43 percentage change | Standard Error 3.798 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time | Week 24 | -43.67 percentage change | Standard Error 3.77 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time | Week 20 | -48.70 percentage change | Standard Error 5.928 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time | Week 8 | -41.01 percentage change | Standard Error 4.217 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time | Week 36 | -34.49 percentage change | Standard Error 3.809 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time | Week 28 | -41.38 percentage change | Standard Error 3.966 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time | Week 16 | -48.48 percentage change | Standard Error 6.947 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time | Week 12 | -42.79 percentage change | Standard Error 4.269 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time | Week 4 | -41.52 percentage change | Standard Error 3.604 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time | Week 28 | -43.95 percentage change | Standard Error 4.039 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time | Week 12 | -41.71 percentage change | Standard Error 4.274 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time | Week 16 | -51.99 percentage change | Standard Error 6.942 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time | Week 20 | -52.73 percentage change | Standard Error 5.942 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time | Week 24 | -49.01 percentage change | Standard Error 3.777 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time | Week 36 | -38.33 percentage change | Standard Error 3.85 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time | Week 4 | -52.22 percentage change | Standard Error 3.658 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time | Week 8 | -47.73 percentage change | Standard Error 4.25 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time | Week 12 | -49.84 percentage change | Standard Error 4.183 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time | Week 16 | -58.73 percentage change | Standard Error 6.82 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time | Week 8 | -52.55 percentage change | Standard Error 4.257 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time | Week 4 | -56.21 percentage change | Standard Error 3.619 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time | Week 20 | -57.97 percentage change | Standard Error 5.79 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time | Week 36 | -51.63 percentage change | Standard Error 3.75 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time | Week 28 | -54.39 percentage change | Standard Error 3.92 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time | Week 24 | -55.57 percentage change | Standard Error 3.726 |
Comparison: Week 4p-value: <0.000195% CI: [-58.53, -38.51]Mixed Model Repeated Measures (MMRM)
Comparison: Week 4p-value: <0.000195% CI: [-69.3, -49.12]Mixed Model Repeated Measures (MMRM)
Comparison: Week 4p-value: <0.000195% CI: [-73.24, -53.18]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: <0.000195% CI: [-66.31, -42.89]m
Comparison: Week 8p-value: <0.000195% CI: [-73.07, -49.55]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: <0.000195% CI: [-77.9, -54.37]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: <0.000195% CI: [-56.91, -33.01]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: <0.000195% CI: [-55.83, -31.92]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: <0.000195% CI: [-63.83, -40.18]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: <0.000195% CI: [-85.04, -46.29]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: <0.000195% CI: [-88.54, -49.8]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: <0.000195% CI: [-95.11, -56.71]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: <0.000195% CI: [-76.78, -43.71]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: <0.000195% CI: [-80.83, -47.72]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: <0.000195% CI: [-85.85, -53.18]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: <0.000195% CI: [-61.73, -40.7]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: <0.000195% CI: [-67.09, -46.04]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: <0.000195% CI: [-73.56, -52.66]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: <0.000195% CI: [-59.66, -37.59]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: <0.000195% CI: [-62.32, -40.05]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: <0.000195% CI: [-72.6, -50.67]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: <0.000195% CI: [-44.65, -23.46]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: <0.000195% CI: [-48.56, -27.25]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: <0.000195% CI: [-61.71, -40.68]Mixed Model Repeated Measures (MMRM)
Secondary
Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period
Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -40.67 percentage change | Standard Error 5.792 |
| Placebo | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -47.14 percentage change | Standard Error 4.687 |
| Placebo | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -48.23 percentage change | Standard Error 11.315 |
| Placebo | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -41.86 percentage change | Standard Error 9.334 |
| Placebo | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -48.07 percentage change | Standard Error 6.892 |
| Placebo | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -47.40 percentage change | Standard Error 6.442 |
| Placebo | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -43.74 percentage change | Standard Error 5.555 |
| Placebo | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -10.02 percentage change | Standard Error 8.711 |
| Placebo | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -40.57 percentage change | Standard Error 9.384 |
| Placebo | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -45.81 percentage change | Standard Error 7.065 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -45.32 percentage change | Standard Error 3.994 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -34.78 percentage change | Standard Error 3.941 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -45.78 percentage change | Standard Error 4.449 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -42.51 percentage change | Standard Error 3.294 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -48.67 percentage change | Standard Error 4.081 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -47.10 percentage change | Standard Error 3.546 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -47.33 percentage change | Standard Error 3.969 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -48.48 percentage change | Standard Error 3.041 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -45.95 percentage change | Standard Error 3.609 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -53.83 percentage change | Standard Error 3.49 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -42.05 percentage change | Standard Error 8.623 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -55.29 percentage change | Standard Error 5.17 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -2.09 percentage change | Standard Error 13.925 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -48.62 percentage change | Standard Error 7.597 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -48.96 percentage change | Standard Error 7.586 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -50.45 percentage change | Standard Error 7.323 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -52.40 percentage change | Standard Error 6.578 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -58.42 percentage change | Standard Error 3.043 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -61.61 percentage change | Standard Error 8.343 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -58.81 percentage change | Standard Error 4.31 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -56.23 percentage change | Standard Error 2.968 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -55.11 percentage change | Standard Error 3.039 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -52.86 percentage change | Standard Error 3.051 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -56.65 percentage change | Standard Error 3.545 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -55.23 percentage change | Standard Error 3.101 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -39.64 percentage change | Standard Error 3.357 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -50.56 percentage change | Standard Error 4.288 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -46.81 percentage change | Standard Error 3.828 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -48.07 percentage change | Standard Error 3.255 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -51.51 percentage change | Standard Error 2.712 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -44.56 percentage change | Standard Error 4.44 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -40.73 percentage change | Standard Error 8.993 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -46.34 percentage change | Standard Error 8.818 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -49.06 percentage change | Standard Error 3.275 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | 7.87 percentage change | Standard Error 12.061 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -49.25 percentage change | Standard Error 4.86 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -51.88 percentage change | Standard Error 3.705 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -49.30 percentage change | Standard Error 4.388 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -48.98 percentage change | Standard Error 6.568 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -49.57 percentage change | Standard Error 5.99 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -58.36 percentage change | Standard Error 2.11 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -58.96 percentage change | Standard Error 3.563 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -62.76 percentage change | Standard Error 2.262 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -58.66 percentage change | Standard Error 2.135 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -57.14 percentage change | Standard Error 2.697 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -53.57 percentage change | Standard Error 4.055 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -56.59 percentage change | Standard Error 2.225 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -51.71 percentage change | Standard Error 4.761 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -51.88 percentage change | Standard Error 2.612 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -47.42 percentage change | Standard Error 6.81 |
Secondary
Percent Change From Baseline in Fasting Total ApoB Over Time
Time frame: Baseline, up to Week 36 (double-blind treatment period)
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 4 | 2.57 percentage change | Standard Error 2.074 |
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 8 | 1.51 percentage change | Standard Error 2.518 |
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 12 | 2.26 percentage change | Standard Error 2.656 |
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 16 | -1.36 percentage change | Standard Error 2.524 |
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 20 | -0.28 percentage change | Standard Error 2.35 |
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 24 | 2.27 percentage change | Standard Error 2.807 |
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 28 | 0.51 percentage change | Standard Error 2.688 |
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 36 | -2.30 percentage change | Standard Error 2.777 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 24 | -16.40 percentage change | Standard Error 2.835 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 20 | -17.99 percentage change | Standard Error 2.37 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 8 | -15.85 percentage change | Standard Error 2.553 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 36 | -12.85 percentage change | Standard Error 2.801 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 28 | -15.39 percentage change | Standard Error 2.725 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 16 | -15.72 percentage change | Standard Error 2.543 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 12 | -14.96 percentage change | Standard Error 2.653 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 4 | -14.00 percentage change | Standard Error 2.116 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 28 | -12.47 percentage change | Standard Error 2.703 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 12 | -7.69 percentage change | Standard Error 2.617 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 16 | -14.33 percentage change | Standard Error 2.513 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 20 | -14.52 percentage change | Standard Error 2.329 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 24 | -12.91 percentage change | Standard Error 2.805 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 36 | -9.07 percentage change | Standard Error 2.791 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 4 | -11.71 percentage change | Standard Error 2.093 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 8 | -10.66 percentage change | Standard Error 2.525 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 12 | -15.10 percentage change | Standard Error 2.606 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 16 | -21.66 percentage change | Standard Error 2.509 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 8 | -15.05 percentage change | Standard Error 2.556 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 4 | -18.47 percentage change | Standard Error 2.105 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 20 | -18.58 percentage change | Standard Error 2.326 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 36 | -13.21 percentage change | Standard Error 2.756 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 28 | -17.03 percentage change | Standard Error 2.68 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time | Week 24 | -19.64 percentage change | Standard Error 2.788 |
Comparison: Week 4p-value: <0.000195% CI: [-22.41, -10.74]Mixed Model Repeated Measures (MMRM)
Comparison: Week 4p-value: <0.000195% CI: [-20.08, -8.48]Mixed Model Repeated Measures (MMRM)
Comparison: Week 4p-value: <0.000195% CI: [-26.85, -15.23]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: <0.000195% CI: [-24.42, -10.29]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: 0.000895% CI: [-19.19, -5.13]Mixed Model Repeated Measures (MMRM)
Comparison: Week 8p-value: <0.000195% CI: [-23.62, -9.5]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: <0.000195% CI: [-24.61, -9.81]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: 0.008295% CI: [-17.3, -2.6]Mixed Model Repeated Measures (MMRM)
Comparison: Week 12p-value: <0.000195% CI: [-24.68, -10.03]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: <0.000195% CI: [-21.42, -7.3]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: 0.000395% CI: [-19.98, -5.95]Mixed Model Repeated Measures (MMRM)
Comparison: Week 16p-value: <0.000195% CI: [-27.3, -13.29]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: <0.000195% CI: [-24.29, -11.13]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: <0.000195% CI: [-20.75, -7.72]Mixed Model Repeated Measures (MMRM)
Comparison: Week 20p-value: <0.000195% CI: [-24.8, -11.79]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: <0.000195% CI: [-26.53, -10.8]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: 0.000295% CI: [-23, -7.36]Mixed Model Repeated Measures (MMRM)
Comparison: Week 24p-value: <0.000195% CI: [-29.69, -14.12]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: <0.000195% CI: [-23.44, -8.35]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: 0.000895% CI: [-20.49, -5.46]Mixed Model Repeated Measures (MMRM)
Comparison: Week 28p-value: <0.000195% CI: [-25.01, -10.07]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: 0.008195% CI: [-18.32, -2.77]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: 0.087195% CI: [-14.52, 0.99]Mixed Model Repeated Measures (MMRM)
Comparison: Week 36p-value: 0.005895% CI: [-18.61, -3.2]Mixed Model Repeated Measures (MMRM)
Secondary
Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period
Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization. Observed cases.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | 0.31 percentage change | Standard Error 8.213 |
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -6.57 percentage change | Standard Error 11.292 |
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -3.46 percentage change | Standard Error 9.733 |
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -14.34 percentage change | Standard Error 5.296 |
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | 6.82 percentage change | — |
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -8.08 percentage change | Standard Error 9.722 |
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -5.48 percentage change | Standard Error 13.745 |
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | 6.57 percentage change | Standard Error 8.959 |
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | 0.08 percentage change | Standard Error 10.835 |
| Placebo | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -1.23 percentage change | Standard Error 7.644 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -14.39 percentage change | Standard Error 5.371 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -13.89 percentage change | Standard Error 3.645 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -13.42 percentage change | Standard Error 3.462 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -13.83 percentage change | Standard Error 3.624 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -21.00 percentage change | Standard Error 6.46 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -13.49 percentage change | Standard Error 3.086 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -12.73 percentage change | Standard Error 3.587 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -13.01 percentage change | Standard Error 7.131 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -12.63 percentage change | Standard Error 3.662 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -1.65 percentage change | — |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -10.22 percentage change | Standard Error 4.678 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -3.56 percentage change | Standard Error 6.243 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -0.30 percentage change | Standard Error 3.518 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -13.84 percentage change | Standard Error 3.803 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -13.78 percentage change | Standard Error 6.382 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -13.40 percentage change | Standard Error 3.056 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -14.12 percentage change | Standard Error 3.655 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -21.03 percentage change | Standard Error 3.791 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -24.76 percentage change | Standard Error 4.68 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -7.09 percentage change | Standard Error 5.09 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -7.48 percentage change | Standard Error 2.924 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -15.14 percentage change | Standard Error 3.52 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -16.23 percentage change | Standard Error 2.661 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -7.93 percentage change | Standard Error 5.968 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -16.73 percentage change | Standard Error 4.236 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -19.88 percentage change | Standard Error 2.991 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -4.45 percentage change | — |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -15.03 percentage change | Standard Error 2.91 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -11.91 percentage change | Standard Error 3.517 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -11.27 percentage change | Standard Error 4.524 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -3.88 percentage change | Standard Error 3.08 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -13.13 percentage change | Standard Error 4.275 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -13.63 percentage change | Standard Error 3.819 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -18.14 percentage change | Standard Error 2.81 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -10.27 percentage change | Standard Error 8.79 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -15.70 percentage change | Standard Error 4.187 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -13.87 percentage change | Standard Error 2.996 |
| Placebo/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -11.37 percentage change | Standard Error 16.839 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 15 | -13.05 percentage change | Standard Error 3.53 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 6 | -14.04 percentage change | Standard Error 3.504 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 3 | -8.34 percentage change | Standard Error 3.722 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 1 | -21.63 percentage change | — |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 24 | -18.04 percentage change | Standard Error 4.441 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 21 | -11.85 percentage change | Standard Error 3.789 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 12 | -15.90 percentage change | Standard Error 2.835 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 18 | -13.92 percentage change | Standard Error 3.741 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Month 2 | -7.58 percentage change | Standard Error 6.338 |
| ARO-ANG3 200 mg/ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period | Percent Change from Baseline to OLE Baseline/OLE Day 1 | -11.77 percentage change | Standard Error 3.309 |
Secondary
Percent Change From Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24
Time frame: Baseline, Week 24
Population: Full Analysis Set: All randomized participants who received at least 1 dose of IP during the study period, analyzed according to the treatment assigned at randomization.Observed cases.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24 | 2.27 percentage change | Standard Error 2.807 |
| ARO-ANG3 50 mg | Percent Change From Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24 | -16.40 percentage change | Standard Error 2.835 |
| ARO-ANG3 100 mg | Percent Change From Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24 | -12.91 percentage change | Standard Error 2.805 |
| ARO-ANG3 200 mg | Percent Change From Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24 | -19.64 percentage change | Standard Error 2.788 |
p-value: <0.000195% CI: [-26.53, -10.8]Mixed Models Repeated Measures
p-value: 0.000295% CI: [-23, -7.36]Mixed Models Repeated Measures
p-value: <0.000195% CI: [-29.69, -14.12]Mixed Models Repeated Measures
Secondary
Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period
Time frame: Baseline, Day 1: pre-dose, 15 minutes, 1, 3, 6 hours post-dose; Day 2: 24 hours post-dose; Week 12: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose (double-blind treatment period)
Population: Full PK Analysis Set: All participants who received at least 1 dose of active study drug and had at least 1 PK concentration data value. Observed cases.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, 1 Hour Post-Dose | 76.2131 ng/mL | Standard Deviation 34.4965 |
| Placebo | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, 3 Hours Post-Dose | 78.2496 ng/mL | Standard Deviation 36.47898 |
| Placebo | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 1, 1 Hour Post-Dose | 75.3752 ng/mL | Standard Deviation 31.39048 |
| Placebo | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, 6 Hours Post-Dose | 87.6919 ng/mL | Standard Deviation 37.30155 |
| Placebo | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, 24 Hours Post-Dose | 15.3604 ng/mL | Standard Deviation 13.03807 |
| Placebo | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 1, Pre-Dose | 0.0000 ng/mL | Standard Deviation 0 |
| Placebo | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 1, 3 Hours Post-Dose | 77.9834 ng/mL | Standard Deviation 34.90982 |
| Placebo | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 1, 6 Hours Post-Dose | 83.9751 ng/mL | Standard Deviation 53.53021 |
| Placebo | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, Pre-Dose | 0.0000 ng/mL | Standard Deviation 0 |
| Placebo | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 2, 24 Hours Post-Dose | 13.3369 ng/mL | Standard Deviation 8.85893 |
| Placebo | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 1, 15 Minutes Post-Dose | 57.6941 ng/mL | Standard Deviation 28.05778 |
| Placebo | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, 15 Minutes Post-Dose | 54.2741 ng/mL | Standard Deviation 43.95835 |
| ARO-ANG3 50 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 1, 15 Minutes Post-Dose | 63.5267 ng/mL | Standard Deviation 55.85108 |
| ARO-ANG3 50 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, 1 Hour Post-Dose | 130.2505 ng/mL | Standard Deviation 52.66507 |
| ARO-ANG3 50 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, Pre-Dose | 0.0653 ng/mL | Standard Deviation 0.27695 |
| ARO-ANG3 50 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 1, 3 Hours Post-Dose | 143.7746 ng/mL | Standard Deviation 79.62215 |
| ARO-ANG3 50 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, 3 Hours Post-Dose | 152.0302 ng/mL | Standard Deviation 78.31595 |
| ARO-ANG3 50 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 1, Pre-Dose | 2.6685 ng/mL | Standard Deviation 12.22871 |
| ARO-ANG3 50 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 2, 24 Hours Post-Dose | 33.3047 ng/mL | Standard Deviation 16.31049 |
| ARO-ANG3 50 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, 6 Hours Post-Dose | 154.3280 ng/mL | Standard Deviation 71.93043 |
| ARO-ANG3 50 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 1, 1 Hour Post-Dose | 130.3387 ng/mL | Standard Deviation 81.73501 |
| ARO-ANG3 50 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 1, 6 Hours Post-Dose | 152.0097 ng/mL | Standard Deviation 91.30854 |
| ARO-ANG3 50 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, 24 Hours Post-Dose | 36.2506 ng/mL | Standard Deviation 18.33432 |
| ARO-ANG3 50 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, 15 Minutes Post-Dose | 68.3054 ng/mL | Standard Deviation 52.28977 |
| ARO-ANG3 100 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, 24 Hours Post-Dose | 103.1401 ng/mL | Standard Deviation 60.85616 |
| ARO-ANG3 100 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 1, Pre-Dose | 0.0000 ng/mL | Standard Deviation 0 |
| ARO-ANG3 100 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 1, 15 Minutes Post-Dose | 154.7823 ng/mL | Standard Deviation 129.4319 |
| ARO-ANG3 100 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 1, 1 Hour Post-Dose | 221.5979 ng/mL | Standard Deviation 105.15447 |
| ARO-ANG3 100 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 1, 3 Hours Post-Dose | 259.2799 ng/mL | Standard Deviation 144.46149 |
| ARO-ANG3 100 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 1, 6 Hours Post-Dose | 280.0843 ng/mL | Standard Deviation 153.62465 |
| ARO-ANG3 100 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, Pre-Dose | 1.9366 ng/mL | Standard Deviation 7.7465 |
| ARO-ANG3 100 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, 15 Minutes Post-Dose | 134.0610 ng/mL | Standard Deviation 138.22698 |
| ARO-ANG3 100 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, 1 Hour Post-Dose | 247.9728 ng/mL | Standard Deviation 112.83368 |
| ARO-ANG3 100 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, 3 Hours Post-Dose | 304.2006 ng/mL | Standard Deviation 178.69258 |
| ARO-ANG3 100 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Week 12, 6 Hours Post-Dose | 312.6397 ng/mL | Standard Deviation 174.86753 |
| ARO-ANG3 100 mg | Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period | Day 2, 24 Hours Post-Dose | 77.9982 ng/mL | Standard Deviation 31.94202 |