NASH
Conditions
Keywords
NASH, NAFLD, Liver diseases, Fatty Liver, Metabolic diseases
Brief summary
Part 1: This is a multi-center evaluation of pegozafermin (administered weekly or every other week) in a randomized, double-blind, placebo-controlled study administered for 12 weeks in participants with NASH and NAFLD at high risk of NASH, including a pre-defined number of participants with biopsy confirmed NASH and fibrosis stages F1-F3 to be enrolled. Part 2: This is a multi-center, open label evaluation of pegozafermin at 27 mg administered weekly for 20 weeks in participants with biopsy-proven NASH (NAS ≥4, fibrosis stage F2 or F3).
Interventions
DRUGPegozafermin
Subcutaneous injection
OTHERPlacebo
Subcutaneous injection
Sponsors
ProSciento, Inc.
89bio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Part 1 was blinded, Part 2 was open label
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participants must be 21 to 75 years of age inclusive, at the time of signing the informed consent form (ICF). * Evidence of steatosis by Fibroscan and magnetic resonance imaging based proton density fat fraction (MRI-PDFF) * NASH or NAFLD at high risk for NASH as reflected by AT LEAST ONE of the following: * Diagnosis of NASH with fibrosis (stages F1, F2 or F3), without cirrhosis, by percutaneous liver biopsy within 24 months prior to screening * Central obesity WITH type 2 diabetes mellitus (T2DM) * Central obesity WITH either increased alanine transaminase (ALT) and/or Fibroscan vibration-controlled transient elastography (VCTE) score ≥7 KPa. * Part 2 only: Biopsy-proven NASH in a liver biopsy obtained within 24 weeks of baseline with fibrosis stage F2 or F3 and NAS ≥4, with a score of at least 1 in each of steatosis, ballooning degeneration, and lobular inflammation. A small number of high risk F1 allowed. Key
Exclusion criteria
* Clinically significant disorder or a history of any illness that, in the opinion of the Investigator, might confound the results of the study, or pose additional risk to the participant by participation in the study. * History of type 1 diabetes. * Weight loss of more than 5% within 3 months prior to Day -1 or more than 10% within 6 months prior to Day -1 or planning to try to lose weight during conduct of study. * History of a liver disorder other than NASH or clinical suspicion of a liver disorder other than NASH * History of cirrhosis or evidence of cirrhosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs) | Up to 113 days | An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were defined as AEs occurring at or after the first dose date and time, through study termination, or existing prior to the time of and worsening after the time of the first dose of investigational product. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Part 2: Number of Participants With TEAEs | Up to 162 days | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were defined as AEs occurring at or after the first dose date and time, through study termination, or existing prior to the time of and worsening after the time of the first dose of investigational product. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin | Predose and up to 168 hours postdose on Day 29 | — |
| Part 1: Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Pegozafermin | Predose and up to 168 hours postdose on Day 29 | — |
| Part 1: Time to Peak Serum Concentration (Tmax) of Pegozafermin | Predose and up to 168 hours postdose on Day 29 | — |
| Part 1: Terminal Elimination Half-life (t1/2) of Pegozafermin | Predose and up to 168 hours postdose on Day 29 | — |
| Part 2: Number of Participants With at Least a 2-point Improvement in NAFLD Activity Score (NAS) With at Least a 1-point Improvement in Ballooning or Lobular Inflammation, and no Worsening of Fibrosis | Day 141 | NAS was the sum of the scores of steatosis, inflammation, and ballooning. NAS score ranges from of 0 to 8, with higher scores indicating worse disease severity. Worsening of fibrosis was defined as progression of fibrosis ≥1 stage in NASH Clinical Research Network (CRN) fibrosis score. NASH CRN Fibrosis is staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Parts 1 and 2: Percent Change From Baseline in Liver Fat as Assessed Via Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) | Part 1: Baseline, Day 92; Part 2: Baseline, Day 141 | LS Mean was calculated using MMRM. |
| Part 1: Percent Change From Baseline in Adiponectin at Day 92 | Baseline, Day 92 | LS Mean was calculated using MMRM. |
| Part 2: Number of Participants With NASH Resolution Without Worsening of Fibrosis | Day 141 | Resolution of NASH included the total absence of ballooning (score=0) and absent or mild inflammation (score 0 to 1). Worsening of fibrosis was defined as progression of fibrosis ≥1 stage in NASH CRN fibrosis score. NASH CRN Fibrosis was staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis). |
| Part 2: Number of Participants With at Least an Improvement of Fibrosis ≥1 Stage Without Worsening of NASH | Day 141 | Fibrosis improvement was defined as ≥1-stage decrease in NASH CRN fibrosis score. Worsening of NASH was defined as increase ≥1 point in NAS for ballooning or inflammation. NASH CRN Fibrosis was staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis). |
| Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92 | Baseline, Day 92 | LS Mean was calculated using MMRM. |
| Part 1: Number of Participants With a Positive Anti-Drug Antibodies (ADA) Response to Pegozafermin | Up to 113 days | Number of participants with anti-pegozafermin antibodies (ADA) with status as ADA positive has been reported. |
| Parts 1 and 2: Percent Change From Baseline in Body Weight | Part 1: Baseline, Day 85; Part 2: Baseline, Day 141 | Least Squares (LS) Mean was calculated using mixed-model repeated measures (MMRM). |
| Part 1: Percent Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR) at Day 50 | Baseline, Day 50 | LS Mean was calculated using MMRM. Adipo-IR was derived from fasting insulin and free fatty acid. |
| Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Part 1: Baseline, Day 92; Part 2: Baseline, Day 141 | LS Mean was calculated using MMRM. |
| Part 1: Percent Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Day 92 | Baseline, Day 92 | LS Mean was calculated using MMRM. HOMA-IR value was calculated by multiplying fasting Glucose (mg/dL) with fasting Insulin (uIU/ml) and then dividing by 405. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Pegozafermin 3 mg QW Participants were administered 3 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85. | 6 |
| Part 1: Pegozafermin 9 mg QW Participants were administered 9 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85. | 12 |
| Part 1: Pegozafermin 18 mg QW Participants were administered 18 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85. | 11 |
| Part 1: Pegozafermin 27 mg QW Participants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85. | 10 |
| Part 1: Pegozafermin 18 mg Q2W Participants were administered 18 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85. | 14 |
| Part 1: Pegozafermin 36 mg Q2W Participants were administered 36 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85. | 9 |
| Part 1: Placebo QW or Q2W Participants were administered placebo matching to pegozafermin QW or Q2W, via SC injection, starting on Day 1 through Day 85. | 19 |
| Part 2: Pegozafermin 27 mg QW Participants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 134. | 20 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 1 | 2 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Part 1: Pegozafermin 3 mg QW | Part 1: Pegozafermin 9 mg QW | Part 1: Pegozafermin 18 mg QW | Part 1: Pegozafermin 27 mg QW | Part 1: Pegozafermin 18 mg Q2W | Part 1: Pegozafermin 36 mg Q2W | Part 1: Placebo QW or Q2W | Part 2: Pegozafermin 27 mg QW | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 56.13 years STANDARD_DEVIATION 8.23 | 49.50 years STANDARD_DEVIATION 11.45 | 51.47 years STANDARD_DEVIATION 13.39 | 51.96 years STANDARD_DEVIATION 9.83 | 51.22 years STANDARD_DEVIATION 8.14 | 52.46 years STANDARD_DEVIATION 8.73 | 52.62 years STANDARD_DEVIATION 8.99 | 58.44 years STANDARD_DEVIATION 9.07 | 52.97 years STANDARD_DEVIATION 1.81 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 11 Participants | 9 Participants | 10 Participants | 13 Participants | 9 Participants | 16 Participants | 5 Participants | 79 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 15 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 11 Participants | 9 Participants | 10 Participants | 13 Participants | 9 Participants | 17 Participants | 20 Participants | 94 Participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 8 Participants | 8 Participants | 10 Participants | 1 Participants | 12 Participants | 15 Participants | 65 Participants |
| Sex: Female, Male Male | 1 Participants | 6 Participants | 3 Participants | 2 Participants | 4 Participants | 8 Participants | 7 Participants | 5 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 12 | 0 / 11 | 0 / 10 | 0 / 14 | 0 / 9 | 0 / 18 | 0 / 20 |
| other Total, other adverse events | 6 / 7 | 4 / 12 | 7 / 11 | 7 / 10 | 8 / 14 | 8 / 9 | 8 / 18 | 18 / 20 |
| serious Total, serious adverse events | 0 / 7 | 0 / 12 | 0 / 11 | 0 / 10 | 1 / 14 | 1 / 9 | 0 / 18 | 0 / 20 |
Outcome results
Primary
Part 1: Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Pegozafermin
Time frame: Predose and up to 168 hours postdose on Day 29
Population: The PK Analysis set included all randomized participants who received at least 1 dose of study intervention and had at least 1 on-study PK measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Part 1: Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Pegozafermin | 11879 ng*hour/mL |
| Part 1: Pegozafermin 9 mg QW | Part 1: Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Pegozafermin | 42576 ng*hour/mL |
| Part 1: Pegozafermin 18 mg QW | Part 1: Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Pegozafermin | 95765 ng*hour/mL |
| Part 1: Pegozafermin 27 mg QW | Part 1: Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Pegozafermin | 112632 ng*hour/mL |
| Part 1: Pegozafermin 18 mg Q2W | Part 1: Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Pegozafermin | 78761 ng*hour/mL |
| Part 1: Pegozafermin 36 mg Q2W | Part 1: Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Pegozafermin | 209436 ng*hour/mL |
Primary
Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin
Time frame: Predose and up to 168 hours postdose on Day 29
Population: The PK Analysis set included all randomized participants who received at least 1 dose of study intervention and had at least 1 on-study PK measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin | 103 ng/mL |
| Part 1: Pegozafermin 9 mg QW | Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin | 439 ng/mL |
| Part 1: Pegozafermin 18 mg QW | Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin | 901 ng/mL |
| Part 1: Pegozafermin 27 mg QW | Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin | 1166 ng/mL |
| Part 1: Pegozafermin 18 mg Q2W | Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin | 649 ng/mL |
| Part 1: Pegozafermin 36 mg Q2W | Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin | 1674 ng/mL |
Primary
Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were defined as AEs occurring at or after the first dose date and time, through study termination, or existing prior to the time of and worsening after the time of the first dose of investigational product. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Up to 113 days
Population: The Safety Analysis set included all randomized participants who received at least 1 dose of study intervention. Arm groups were based upon the actual treatment received for the purpose of safety analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs) | 6 Participants |
| Part 1: Pegozafermin 9 mg QW | Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs) | 4 Participants |
| Part 1: Pegozafermin 18 mg QW | Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs) | 7 Participants |
| Part 1: Pegozafermin 27 mg QW | Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs) | 7 Participants |
| Part 1: Pegozafermin 18 mg Q2W | Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs) | 8 Participants |
| Part 1: Pegozafermin 36 mg Q2W | Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs) | 8 Participants |
| Part 1: Placebo QW or Q2W | Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs) | 8 Participants |
Primary
Part 1: Terminal Elimination Half-life (t1/2) of Pegozafermin
Time frame: Predose and up to 168 hours postdose on Day 29
Population: The PK Analysis set included all randomized participants who received at least 1 dose of study intervention and had at least 1 on-study PK measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Part 1: Terminal Elimination Half-life (t1/2) of Pegozafermin | 57.1 hr |
| Part 1: Pegozafermin 9 mg QW | Part 1: Terminal Elimination Half-life (t1/2) of Pegozafermin | 46.3 hr |
| Part 1: Pegozafermin 18 mg QW | Part 1: Terminal Elimination Half-life (t1/2) of Pegozafermin | 68.1 hr |
| Part 1: Pegozafermin 27 mg QW | Part 1: Terminal Elimination Half-life (t1/2) of Pegozafermin | 53.0 hr |
| Part 1: Pegozafermin 18 mg Q2W | Part 1: Terminal Elimination Half-life (t1/2) of Pegozafermin | 54.4 hr |
| Part 1: Pegozafermin 36 mg Q2W | Part 1: Terminal Elimination Half-life (t1/2) of Pegozafermin | 53.2 hr |
Primary
Part 1: Time to Peak Serum Concentration (Tmax) of Pegozafermin
Time frame: Predose and up to 168 hours postdose on Day 29
Population: The PK Analysis set included all randomized participants who received at least 1 dose of study intervention and had at least 1 on-study PK measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Part 1: Time to Peak Serum Concentration (Tmax) of Pegozafermin | 59.5 hr |
| Part 1: Pegozafermin 9 mg QW | Part 1: Time to Peak Serum Concentration (Tmax) of Pegozafermin | 48.0 hr |
| Part 1: Pegozafermin 18 mg QW | Part 1: Time to Peak Serum Concentration (Tmax) of Pegozafermin | 48.0 hr |
| Part 1: Pegozafermin 27 mg QW | Part 1: Time to Peak Serum Concentration (Tmax) of Pegozafermin | 48.1 hr |
| Part 1: Pegozafermin 18 mg Q2W | Part 1: Time to Peak Serum Concentration (Tmax) of Pegozafermin | 72.0 hr |
| Part 1: Pegozafermin 36 mg Q2W | Part 1: Time to Peak Serum Concentration (Tmax) of Pegozafermin | 48.0 hr |
Primary
Part 2: Number of Participants With at Least a 2-point Improvement in NAFLD Activity Score (NAS) With at Least a 1-point Improvement in Ballooning or Lobular Inflammation, and no Worsening of Fibrosis
NAS was the sum of the scores of steatosis, inflammation, and ballooning. NAS score ranges from of 0 to 8, with higher scores indicating worse disease severity. Worsening of fibrosis was defined as progression of fibrosis ≥1 stage in NASH Clinical Research Network (CRN) fibrosis score. NASH CRN Fibrosis is staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
Time frame: Day 141
Population: The Histology Biopsy Analysis Set included all enrolled participants who received at least 1 dose of study intervention and who had both baseline (screening or eligible historical) and post-baseline biopsies.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Part 2: Number of Participants With at Least a 2-point Improvement in NAFLD Activity Score (NAS) With at Least a 1-point Improvement in Ballooning or Lobular Inflammation, and no Worsening of Fibrosis | 12 Participants |
Primary
Part 2: Number of Participants With TEAEs
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were defined as AEs occurring at or after the first dose date and time, through study termination, or existing prior to the time of and worsening after the time of the first dose of investigational product. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Up to 162 days
Population: The Full Analysis Set included all enrolled participants in Part 2 who received at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Part 2: Number of Participants With TEAEs | 18 Participants |
Secondary
Part 1: Number of Participants With a Positive Anti-Drug Antibodies (ADA) Response to Pegozafermin
Number of participants with anti-pegozafermin antibodies (ADA) with status as ADA positive has been reported.
Time frame: Up to 113 days
Population: The Safety Analysis set included all randomized participants who received at least 1 dose of study intervention. Arm groups were based upon the actual treatment received for the purpose of safety analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Part 1: Number of Participants With a Positive Anti-Drug Antibodies (ADA) Response to Pegozafermin | 1 Participants |
| Part 1: Pegozafermin 9 mg QW | Part 1: Number of Participants With a Positive Anti-Drug Antibodies (ADA) Response to Pegozafermin | 9 Participants |
| Part 1: Pegozafermin 18 mg QW | Part 1: Number of Participants With a Positive Anti-Drug Antibodies (ADA) Response to Pegozafermin | 7 Participants |
| Part 1: Pegozafermin 27 mg QW | Part 1: Number of Participants With a Positive Anti-Drug Antibodies (ADA) Response to Pegozafermin | 7 Participants |
| Part 1: Pegozafermin 18 mg Q2W | Part 1: Number of Participants With a Positive Anti-Drug Antibodies (ADA) Response to Pegozafermin | 11 Participants |
| Part 1: Pegozafermin 36 mg Q2W | Part 1: Number of Participants With a Positive Anti-Drug Antibodies (ADA) Response to Pegozafermin | 6 Participants |
| Part 1: Placebo QW or Q2W | Part 1: Number of Participants With a Positive Anti-Drug Antibodies (ADA) Response to Pegozafermin | 2 Participants |
Secondary
Part 1: Percent Change From Baseline in Adiponectin at Day 92
LS Mean was calculated using MMRM.
Time frame: Baseline, Day 92
Population: The analysis set included all randomized participants who received at least 1 dose of investigational product and who had measurable post-baseline PD data in Part 1. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Part 1: Percent Change From Baseline in Adiponectin at Day 92 | 37.65 Percent change | Standard Error 14.48 |
| Part 1: Pegozafermin 9 mg QW | Part 1: Percent Change From Baseline in Adiponectin at Day 92 | 25.46 Percent change | Standard Error 9.88 |
| Part 1: Pegozafermin 18 mg QW | Part 1: Percent Change From Baseline in Adiponectin at Day 92 | 29.09 Percent change | Standard Error 10.47 |
| Part 1: Pegozafermin 27 mg QW | Part 1: Percent Change From Baseline in Adiponectin at Day 92 | 60.85 Percent change | Standard Error 12 |
| Part 1: Pegozafermin 18 mg Q2W | Part 1: Percent Change From Baseline in Adiponectin at Day 92 | 23.11 Percent change | Standard Error 9.07 |
| Part 1: Pegozafermin 36 mg Q2W | Part 1: Percent Change From Baseline in Adiponectin at Day 92 | 24.14 Percent change | Standard Error 12.1 |
| Part 1: Placebo QW or Q2W | Part 1: Percent Change From Baseline in Adiponectin at Day 92 | -4.25 Percent change | Standard Error 7.8 |
Secondary
Part 1: Percent Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR) at Day 50
LS Mean was calculated using MMRM. Adipo-IR was derived from fasting insulin and free fatty acid.
Time frame: Baseline, Day 50
Population: The analysis set included all randomized participants who received at least 1 dose of study intervention and who had measurable post-baseline PD data in Part 1. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Part 1: Percent Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR) at Day 50 | -6.12 Percent change | Standard Error 61.71 |
| Part 1: Pegozafermin 9 mg QW | Part 1: Percent Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR) at Day 50 | 82.00 Percent change | Standard Error 59.79 |
| Part 1: Pegozafermin 18 mg QW | Part 1: Percent Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR) at Day 50 | 3.28 Percent change | Standard Error 60.01 |
| Part 1: Pegozafermin 27 mg QW | Part 1: Percent Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR) at Day 50 | 78.40 Percent change | Standard Error 46.41 |
| Part 1: Pegozafermin 18 mg Q2W | Part 1: Percent Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR) at Day 50 | -25.96 Percent change | Standard Error 42.75 |
| Part 1: Pegozafermin 36 mg Q2W | Part 1: Percent Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR) at Day 50 | -10.36 Percent change | Standard Error 50.33 |
| Part 1: Placebo QW or Q2W | Part 1: Percent Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR) at Day 50 | -15.82 Percent change | Standard Error 32.62 |
Secondary
Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92
LS Mean was calculated using MMRM.
Time frame: Baseline, Day 92
Population: The analysis set included all randomized participants who received at least 1 dose of study intervention and who had measurable post-baseline PD data in Part 1. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92 | 28.70 Percent change | Standard Error 24.68 |
| Part 1: Pegozafermin 9 mg QW | Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92 | 50.20 Percent change | Standard Error 21.05 |
| Part 1: Pegozafermin 18 mg QW | Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92 | 27.08 Percent change | Standard Error 17.76 |
| Part 1: Pegozafermin 27 mg QW | Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92 | 51.58 Percent change | Standard Error 22.08 |
| Part 1: Pegozafermin 18 mg Q2W | Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92 | 43.85 Percent change | Standard Error 18.17 |
| Part 1: Pegozafermin 36 mg Q2W | Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92 | 56.12 Percent change | Standard Error 20.81 |
| Part 1: Placebo QW or Q2W | Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92 | 20.91 Percent change | Standard Error 13.96 |
Secondary
Part 1: Percent Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Day 92
LS Mean was calculated using MMRM. HOMA-IR value was calculated by multiplying fasting Glucose (mg/dL) with fasting Insulin (uIU/ml) and then dividing by 405.
Time frame: Baseline, Day 92
Population: The analysis set included all randomized participants who received at least 1 dose of investigational product and who had measurable post-baseline PD data in Part 1. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Part 1: Percent Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Day 92 | 10.37 Percent change | Standard Error 51.3 |
| Part 1: Pegozafermin 9 mg QW | Part 1: Percent Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Day 92 | 7.40 Percent change | Standard Error 30.62 |
| Part 1: Pegozafermin 18 mg QW | Part 1: Percent Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Day 92 | 37.07 Percent change | Standard Error 20.87 |
| Part 1: Pegozafermin 27 mg QW | Part 1: Percent Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Day 92 | -41.42 Percent change | Standard Error 19.48 |
| Part 1: Pegozafermin 18 mg Q2W | Part 1: Percent Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Day 92 | -4.57 Percent change | Standard Error 15.57 |
| Part 1: Pegozafermin 36 mg Q2W | Part 1: Percent Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Day 92 | -41.11 Percent change | Standard Error 23.39 |
| Part 1: Placebo QW or Q2W | Part 1: Percent Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Day 92 | -0.09 Percent change | Standard Error 15.72 |
Secondary
Part 2: Number of Participants With at Least an Improvement of Fibrosis ≥1 Stage Without Worsening of NASH
Fibrosis improvement was defined as ≥1-stage decrease in NASH CRN fibrosis score. Worsening of NASH was defined as increase ≥1 point in NAS for ballooning or inflammation. NASH CRN Fibrosis was staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
Time frame: Day 141
Population: The Histology Biopsy Analysis Set included all enrolled participants who received at least 1 dose of study intervention and who had both baseline (screening or eligible historical) and post-baseline biopsies.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Part 2: Number of Participants With at Least an Improvement of Fibrosis ≥1 Stage Without Worsening of NASH | 5 Participants |
Secondary
Part 2: Number of Participants With NASH Resolution Without Worsening of Fibrosis
Resolution of NASH included the total absence of ballooning (score=0) and absent or mild inflammation (score 0 to 1). Worsening of fibrosis was defined as progression of fibrosis ≥1 stage in NASH CRN fibrosis score. NASH CRN Fibrosis was staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
Time frame: Day 141
Population: The Histology Biopsy Analysis Set included all enrolled participants who received at least 1 dose of study intervention and who had both baseline (screening or eligible historical) and post-baseline biopsies.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Part 2: Number of Participants With NASH Resolution Without Worsening of Fibrosis | 6 Participants |
Secondary
Parts 1 and 2: Percent Change From Baseline in Body Weight
Least Squares (LS) Mean was calculated using mixed-model repeated measures (MMRM).
Time frame: Part 1: Baseline, Day 85; Part 2: Baseline, Day 141
Population: The analysis set included all randomized participants who received at least 1 dose of study intervention and who had measurable post-baseline PD data in Parts 1 and 2. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Parts 1 and 2: Percent Change From Baseline in Body Weight | 1.19 Percent change | Standard Error 1.06 |
| Part 1: Pegozafermin 9 mg QW | Parts 1 and 2: Percent Change From Baseline in Body Weight | 2.59 Percent change | Standard Error 0.74 |
| Part 1: Pegozafermin 18 mg QW | Parts 1 and 2: Percent Change From Baseline in Body Weight | 2.47 Percent change | Standard Error 0.79 |
| Part 1: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Body Weight | -0.80 Percent change | Standard Error 0.86 |
| Part 1: Pegozafermin 18 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Body Weight | 2.11 Percent change | Standard Error 0.69 |
| Part 1: Pegozafermin 36 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Body Weight | 2.64 Percent change | Standard Error 0.86 |
| Part 1: Placebo QW or Q2W | Parts 1 and 2: Percent Change From Baseline in Body Weight | 1.38 Percent change | Standard Error 0.59 |
| Part 2: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Body Weight | -3.10 Percent change | Standard Error 0.83 |
Secondary
Parts 1 and 2: Percent Change From Baseline in Liver Fat as Assessed Via Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)
LS Mean was calculated using MMRM.
Time frame: Part 1: Baseline, Day 92; Part 2: Baseline, Day 141
Population: The analysis set included all randomized participants who received at least 1 dose of study intervention and who had measurable post-baseline PD data in Parts 1 and 2. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Parts 1 and 2: Percent Change From Baseline in Liver Fat as Assessed Via Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) | -36.94 Percent change | Standard Error 11.01 |
| Part 1: Pegozafermin 9 mg QW | Parts 1 and 2: Percent Change From Baseline in Liver Fat as Assessed Via Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) | -49.62 Percent change | Standard Error 7.73 |
| Part 1: Pegozafermin 18 mg QW | Parts 1 and 2: Percent Change From Baseline in Liver Fat as Assessed Via Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) | -36.11 Percent change | Standard Error 8.14 |
| Part 1: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Liver Fat as Assessed Via Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) | -60.39 Percent change | Standard Error 9.4 |
| Part 1: Pegozafermin 18 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Liver Fat as Assessed Via Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) | -43.19 Percent change | Standard Error 6.99 |
| Part 1: Pegozafermin 36 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Liver Fat as Assessed Via Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) | -50.39 Percent change | Standard Error 9.07 |
| Part 1: Placebo QW or Q2W | Parts 1 and 2: Percent Change From Baseline in Liver Fat as Assessed Via Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) | 9.77 Percent change | Standard Error 6.04 |
| Part 2: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Liver Fat as Assessed Via Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) | -64.69 Percent change | Standard Error 3.38 |
Secondary
Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3)
LS Mean was calculated using MMRM.
Time frame: Part 1: Baseline, Day 92; Part 2: Baseline, Day 141
Population: The analysis set included all randomized participants who received at least 1 dose of study intervention and who had measurable post-baseline PD data in Parts 1 and 2. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Pegozafermin 3 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Non HDLc | -6.31 Percent change | Standard Error 6.45 |
| Part 1: Pegozafermin 3 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | HDLc | 18.17 Percent change | Standard Error 5.43 |
| Part 1: Pegozafermin 3 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Triglycerides | -22.74 Percent change | Standard Error 11.53 |
| Part 1: Pegozafermin 3 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | LDLc | -6.17 Percent change | Standard Error 7.38 |
| Part 1: Pegozafermin 3 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | HbA1C | 7.36 Percent change | Standard Error 4.05 |
| Part 1: Pegozafermin 3 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Alanine Transaminase | -16.87 Percent change | Standard Error 10.62 |
| Part 1: Pegozafermin 3 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Aspartate Aminotransferase | -29.36 Percent change | Standard Error 9.47 |
| Part 1: Pegozafermin 3 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Pro-C3 | -19.71 Percent change | Standard Error 14.53 |
| Part 1: Pegozafermin 9 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | HbA1C | 1.80 Percent change | Standard Error 2.84 |
| Part 1: Pegozafermin 9 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Non HDLc | -13.87 Percent change | Standard Error 4.61 |
| Part 1: Pegozafermin 9 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Alanine Transaminase | -26.65 Percent change | Standard Error 6.99 |
| Part 1: Pegozafermin 9 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Aspartate Aminotransferase | -19.90 Percent change | Standard Error 6.15 |
| Part 1: Pegozafermin 9 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Triglycerides | -23.95 Percent change | Standard Error 7.74 |
| Part 1: Pegozafermin 9 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | LDLc | -13.45 Percent change | Standard Error 5.29 |
| Part 1: Pegozafermin 9 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | HDLc | 11.19 Percent change | Standard Error 3.68 |
| Part 1: Pegozafermin 9 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Pro-C3 | -18.79 Percent change | Standard Error 9.02 |
| Part 1: Pegozafermin 18 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Aspartate Aminotransferase | -15.10 Percent change | Standard Error 6.52 |
| Part 1: Pegozafermin 18 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | HbA1C | 3.05 Percent change | Standard Error 2.99 |
| Part 1: Pegozafermin 18 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Pro-C3 | 1.08 Percent change | Standard Error 9.38 |
| Part 1: Pegozafermin 18 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Non HDLc | -1.92 Percent change | Standard Error 4.74 |
| Part 1: Pegozafermin 18 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Alanine Transaminase | -26.73 Percent change | Standard Error 7.4 |
| Part 1: Pegozafermin 18 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | LDLc | 2.59 Percent change | Standard Error 5.41 |
| Part 1: Pegozafermin 18 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Triglycerides | -17.71 Percent change | Standard Error 8.2 |
| Part 1: Pegozafermin 18 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | HDLc | 9.20 Percent change | Standard Error 3.92 |
| Part 1: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Pro-C3 | -27.67 Percent change | Standard Error 11.2 |
| Part 1: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | HDLc | 2.90 Percent change | Standard Error 4.5 |
| Part 1: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Triglycerides | -27.63 Percent change | Standard Error 9.66 |
| Part 1: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | LDLc | -16.46 Percent change | Standard Error 6.34 |
| Part 1: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Non HDLc | -16.32 Percent change | Standard Error 5.51 |
| Part 1: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | HbA1C | -3.66 Percent change | Standard Error 3.42 |
| Part 1: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Alanine Transaminase | -43.69 Percent change | Standard Error 8.55 |
| Part 1: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Aspartate Aminotransferase | -37.88 Percent change | Standard Error 7.52 |
| Part 1: Pegozafermin 18 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | LDLc | -5.02 Percent change | Standard Error 5.06 |
| Part 1: Pegozafermin 18 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Aspartate Aminotransferase | -11.41 Percent change | Standard Error 5.63 |
| Part 1: Pegozafermin 18 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Non HDLc | -7.75 Percent change | Standard Error 4.38 |
| Part 1: Pegozafermin 18 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Triglycerides | -28.49 Percent change | Standard Error 8.62 |
| Part 1: Pegozafermin 18 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Pro-C3 | -11.18 Percent change | Standard Error 8.19 |
| Part 1: Pegozafermin 18 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | HbA1C | -1.85 Percent change | Standard Error 2.6 |
| Part 1: Pegozafermin 18 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Alanine Transaminase | -18.83 Percent change | Standard Error 6.38 |
| Part 1: Pegozafermin 18 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | HDLc | 20.10 Percent change | Standard Error 3.73 |
| Part 1: Pegozafermin 36 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Pro-C3 | -12.76 Percent change | Standard Error 11.22 |
| Part 1: Pegozafermin 36 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | HDLc | 9.79 Percent change | Standard Error 4.56 |
| Part 1: Pegozafermin 36 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Non HDLc | -6.34 Percent change | Standard Error 5.39 |
| Part 1: Pegozafermin 36 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Triglycerides | -20.71 Percent change | Standard Error 9.74 |
| Part 1: Pegozafermin 36 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Aspartate Aminotransferase | -25.32 Percent change | Standard Error 7.43 |
| Part 1: Pegozafermin 36 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Alanine Transaminase | -39.84 Percent change | Standard Error 8.42 |
| Part 1: Pegozafermin 36 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | HbA1C | 6.89 Percent change | Standard Error 3.43 |
| Part 1: Pegozafermin 36 mg Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | LDLc | -4.11 Percent change | Standard Error 6.2 |
| Part 1: Placebo QW or Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Non HDLc | 1.18 Percent change | Standard Error 3.56 |
| Part 1: Placebo QW or Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | HDLc | 1.96 Percent change | Standard Error 2.97 |
| Part 1: Placebo QW or Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | LDLc | 1.15 Percent change | Standard Error 4.08 |
| Part 1: Placebo QW or Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | HbA1C | 0.61 Percent change | Standard Error 2.28 |
| Part 1: Placebo QW or Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Alanine Transaminase | -4.18 Percent change | Standard Error 5.47 |
| Part 1: Placebo QW or Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Pro-C3 | 3.26 Percent change | Standard Error 7.02 |
| Part 1: Placebo QW or Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Aspartate Aminotransferase | -4.40 Percent change | Standard Error 4.85 |
| Part 1: Placebo QW or Q2W | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Triglycerides | -2.21 Percent change | Standard Error 6.23 |
| Part 2: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Pro-C3 | -19.52 Percent change | Standard Error 3.28 |
| Part 2: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Alanine Transaminase | -45.80 Percent change | Standard Error 3.86 |
| Part 2: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | HbA1C | -7.23 Percent change | Standard Error 1.66 |
| Part 2: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | LDLc | -12.36 Percent change | Standard Error 4.8 |
| Part 2: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Non HDLc | -17.12 Percent change | Standard Error 3.53 |
| Part 2: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | HDLc | 22.65 Percent change | Standard Error 5.58 |
| Part 2: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Triglycerides | -25.30 Percent change | Standard Error 5.66 |
| Part 2: Pegozafermin 27 mg QW | Parts 1 and 2: Percent Change From Baseline in Triglycerides, High Density Lipoprotein (HDL) Cholesterol (c), Non-HDLc, LDLc, Hemoglobin (HbA1C), Alanine Transaminase, Aspartate Aminotransferase, N-terminal Propeptide of Type III Collagen (Pro-C3) | Aspartate Aminotransferase | -47.28 Percent change | Standard Error 3.54 |