A Multiple Ascending Dose Study of Pegozafermin in Participants With Biopsy Confirmed Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) and at High Risk of NASH

Phase 1

Completed

• Conditions: NASH
• Interventions: Drug: Pegozafermin; Other: Placebo

• Registration Number: NCT04048135
• Lead Sponsor: 89bio, Inc.

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2019-07-29
• Study First Submitted: 2019-08-04
• Study First Submitted QC: 2019-08-06
• Study First Posted: 2019-08-07
• Primary Completion: 2020-08-28
• Study Completion: 2022-01-19
• Status Verified: 2024-02
• Results First Submitted: 2024-03-04
• Results First Submitted QC: 2024-03-04
• Last Update Submitted: 2024-03-04
• Results First Posted: 2024-04-02
• Last Update Posted: 2024-04-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 101

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 2: Pegozafermin 27 mg QW	Pegozafermin	Participants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 134.
Part 1: Pegozafermin 18 mg QW	Pegozafermin	Participants were administered 18 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.
Part 1: Pegozafermin 27 mg QW	Pegozafermin	Participants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.
Part 1: Pegozafermin 18 mg Every 2 Weeks (Q2W)	Pegozafermin	Participants were administered 18 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85.
Part 1: Pegozafermin 3 milligrams (mg) weekly (QW)	Pegozafermin	Participants were administered 3 mg of pegozafermin QW, via subcutaneous (SC) injection, starting on Day 1 through Day 85.
Part 1: Pegozafermin 9 mg QW	Pegozafermin	Participants were administered 9 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.
Part 1: Pegozafermin 36 mg Q2W	Pegozafermin	Participants were administered 36 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85.
Part 1: Placebo QW or Q2W	Placebo	Participants were administered placebo matching to pegozafermin QW or Q2W, via SC injection, starting on Day 1 through Day 85.

Primary Outcome Measures

Name	Time	Method
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 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 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 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 Outcome Measures

Name	Time	Method
Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92	Baseline, Day 92	LS Mean was calculated using MMRM.
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 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 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.
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 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 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 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).

Trial Locations

Locations (1)

89bio Clinical Study Site; 🇵🇷 San Juan, Puerto Rico