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

89bio, Inc.101 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

101

Conditions

NASH

Interventions

Pegozafermin

Eligibility

Sex: ALLMin age: 21 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (26)

89bio Clinical Study Site

Madison, Alabama, United States

89bio Clinical Study Site

Chandler, Arizona, United States

89bio Clinical Study Site

Tucson, Arizona, United States

89bio Clinical Study Site

Chula Vista, California, United States

89bio Clinical Study Site

Huntington Beach, California, United States

89bio Clinical Study Site

Montclair, California, United States

89bio Clinical Study Site

Miami, Florida, United States

89bio Clinical Study Site

Miami Lakes, Florida, United States

89bio Clinical Study Site

Ocala, Florida, United States

89bio Clinical Study Site

Sarasota, Florida, United States

...and 16 more locations

Outcomes

Primary Outcomes

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

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

Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin

Time frame: 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

Time frame: Predose and up to 168 hours postdose on Day 29

Part 1: Time to Peak Serum Concentration (Tmax) of Pegozafermin

Time frame: Predose and up to 168 hours postdose on Day 29

Part 1: Terminal Elimination Half-life (t1/2) of Pegozafermin

Time frame: 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).

Time frame: Day 141

Secondary Outcomes

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

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

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

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

Part 1: Percent Change From Baseline in Adiponectin at Day 92

LS Mean was calculated using MMRM.

Time frame: Baseline, Day 92

Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92

LS Mean was calculated using MMRM.

Time frame: 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.

Time frame: Baseline, Day 50

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

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