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

A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetic Properties of BIO89-100 Administered Subcutaneously in Subjects With Nonalcoholic Steatohepatitis (NASH) or With Nonalcoholic Fatty Liver Disease (NAFLD) and at High Risk of NASH

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).

Study Overview

• Status: Completed
• Conditions: NASH
• Intervention / Treatment: Other: Placebo; Drug: Pegozafermin

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • 89bio Clinical Study Site
• United States
  • Alabama
    • Madison, Alabama, United States, 35758
      • 89bio Clinical Study Site
  • Arizona
    • Chandler, Arizona, United States, 85224
      • 89bio Clinical Study Site
    • Tucson, Arizona, United States, 85712
      • 89bio Clinical Study Site
  • California
    • Chula Vista, California, United States, 91911
      • 89bio Clinical Study Site
    • Huntington Beach, California, United States, 92647
      • 89bio Clinical Study Site
    • Montclair, California, United States, 91763
      • 89bio Clinical Study Site
  • Florida
    • Miami, Florida, United States, 33014-3616
      • 89bio Clinical Study Site
    • Miami Lakes, Florida, United States, 33014
      • 89bio Clinical Study Site
    • Ocala, Florida, United States, 34471
      • 89bio Clinical Study Site
    • Sarasota, Florida, United States, 34240
      • 89bio Clinical Study Site
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • 89bio Clinical Study Site
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • 89bio Clinical Study Site
    • Florham Park, New Jersey, United States, 07932
      • 89bio Clinical Study Site
  • New York
    • East Syracuse, New York, United States, 13057
      • 89bio Clinical Study Site
  • North Carolina
    • Concord, North Carolina, United States, 28027
      • 89bio Clinical Study Site
    • Raleigh, North Carolina, United States, 27612
      • 89bio Clinical Study Site
  • South Carolina
    • Greenwood, South Carolina, United States, 29646
      • 89bio Clinical Study Site
    • Summerville, South Carolina, United States, 29485
      • 89bio Clinical Study Site
  • Tennessee
    • Hermitage, Tennessee, United States, 37076
      • 89bio Clinical Study Site
  • Texas
    • Austin, Texas, United States, 78757
      • 89bio Clinical Study Site
    • Edinburg, Texas, United States, 78539
      • 89bio Clinical Study Site
    • Houston, Texas, United States, 77058
      • 89bio Clinical Study Site
    • San Antonio, Texas, United States, 78215
      • 89bio Clinical Study Site
    • San Antonio, Texas, United States, 78229
      • 89bio Clinical Study Site
    • Wichita Falls, Texas, United States, 76301
      • 89bio Clinical Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Pegozafermin 3 milligrams (mg) weekly (QW); Participants were administered 3 mg of pegozafermin QW, via subcutaneous (SC) injection, starting on Day 1 through Day 85.	Drug: Pegozafermin; Subcutaneous injection; Other Names: BIO89-100
Experimental: Part 1: Pegozafermin 9 mg QW; Participants were administered 9 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.	Drug: Pegozafermin; Subcutaneous injection; Other Names: BIO89-100
Experimental: Part 1: Pegozafermin 18 mg QW; Participants were administered 18 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.	Drug: Pegozafermin; Subcutaneous injection; Other Names: BIO89-100
Experimental: Part 1: Pegozafermin 27 mg QW; Participants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 85.	Drug: Pegozafermin; Subcutaneous injection; Other Names: BIO89-100
Experimental: Part 1: Pegozafermin 18 mg Every 2 Weeks (Q2W); Participants were administered 18 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85.	Drug: Pegozafermin; Subcutaneous injection; Other Names: BIO89-100
Experimental: Part 1: Pegozafermin 36 mg Q2W; Participants were administered 36 mg of pegozafermin Q2W, via SC injection, starting on Day 1 through Day 85.	Drug: Pegozafermin; Subcutaneous injection; Other Names: BIO89-100
Placebo Comparator: 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.	Other: Placebo; Subcutaneous injection
Experimental: Part 2: Pegozafermin 27 mg QW; Participants were administered 27 mg of pegozafermin QW, via SC injection, starting on Day 1 through Day 134.	Drug: Pegozafermin; Subcutaneous injection; Other Names: BIO89-100

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 113 days
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.	Up to 162 days
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	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).	Day 141

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 113 days
Parts 1 and 2: Percent Change From Baseline in Body Weight	Least Squares (LS) Mean was calculated using mixed-model repeated measures (MMRM).	Part 1: Baseline, Day 85; Part 2: Baseline, Day 141
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.	Part 1: Baseline, Day 92; Part 2: Baseline, Day 141
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.	Baseline, Day 92
Part 1: Percent Change From Baseline in Adiponectin at Day 92	LS Mean was calculated using MMRM.	Baseline, Day 92
Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92	LS Mean was calculated using MMRM.	Baseline, Day 92
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.	Baseline, Day 50
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.	Part 1: Baseline, Day 92; Part 2: Baseline, Day 141
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).	Day 141
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).	Day 141

Collaborators and Investigators

• Sponsor: 89bio, Inc.
• Collaborators: ProSciento, Inc.
• Investigators: Study Director: Charlton, MD, 89bio, Inc.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2019
• Primary Completion (Actual): August 28, 2020
• Study Completion (Actual): January 19, 2022

Study Registration Dates

• First Submitted: August 4, 2019
• First Submitted That Met QC Criteria: August 6, 2019
• First Posted (Actual): August 7, 2019

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Fatty Liver; Metabolic diseases; Liver diseases; NASH, NAFLD
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: BIO89-100-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No