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

NASH Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04048135
• Other study ID #: BIO89-100-002
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 29, 2019
• Est. completion date: January 19, 2022

Study information

• Verified date: February 2024
• Source: 89bio, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: January 19, 2022
• Est. primary completion date: August 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• NASH
• Non-alcoholic Fatty Liver Disease

Intervention

Drug:
• Pegozafermin
Subcutaneous injection

Other:
• Placebo
Subcutaneous injection

Locations

Country	Name	City	State
Puerto Rico	89bio Clinical Study Site	San Juan
United States	89bio Clinical Study Site	Austin	Texas
United States	89bio Clinical Study Site	Berlin	New Jersey
United States	89bio Clinical Study Site	Chandler	Arizona
United States	89bio Clinical Study Site	Chula Vista	California
United States	89bio Clinical Study Site	Concord	North Carolina
United States	89bio Clinical Study Site	East Syracuse	New York
United States	89bio Clinical Study Site	Edinburg	Texas
United States	89bio Clinical Study Site	Florham Park	New Jersey
United States	89bio Clinical Study Site	Greenwood	South Carolina
United States	89bio Clinical Study Site	Hermitage	Tennessee
United States	89bio Clinical Study Site	Houston	Texas
United States	89bio Clinical Study Site	Huntington Beach	California
United States	89bio Clinical Study Site	Lake Charles	Louisiana
United States	89bio Clinical Study Site	Madison	Alabama
United States	89bio Clinical Study Site	Miami	Florida
United States	89bio Clinical Study Site	Miami Lakes	Florida
United States	89bio Clinical Study Site	Montclair	California
United States	89bio Clinical Study Site	Ocala	Florida
United States	89bio Clinical Study Site	Raleigh	North Carolina
United States	89bio Clinical Study Site	San Antonio	Texas
United States	89bio Clinical Study Site	San Antonio	Texas
United States	89bio Clinical Study Site	Sarasota	Florida
United States	89bio Clinical Study Site	Summerville	South Carolina
United States	89bio Clinical Study Site	Tucson	Arizona
United States	89bio Clinical Study Site	Wichita Falls	Texas

Sponsors (2)

Lead Sponsor	Collaborator
89bio, Inc.	ProSciento, Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Up to 113 days
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.	Up to 162 days
Primary	Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin		Predose and up to 168 hours postdose on Day 29
Primary	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
Primary	Part 1: Time to Peak Serum Concentration (Tmax) of Pegozafermin		Predose and up to 168 hours postdose on Day 29
Primary	Part 1: Terminal Elimination Half-life (t1/2) of Pegozafermin		Predose and up to 168 hours postdose on Day 29
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).	Day 141
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.	Up to 113 days
Secondary	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
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.	Part 1: Baseline, Day 92; Part 2: Baseline, Day 141
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.	Baseline, Day 92
Secondary	Part 1: Percent Change From Baseline in Adiponectin at Day 92	LS Mean was calculated using MMRM.	Baseline, Day 92
Secondary	Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92	LS Mean was calculated using MMRM.	Baseline, Day 92
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.	Baseline, Day 50
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.	Part 1: Baseline, Day 92; Part 2: Baseline, Day 141
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).	Day 141
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).	Day 141

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