Clinical trial NCT04048135: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: NASH
Keywords: NASH, NAFLD
Liver diseases
Fatty Liver
Metabolic diseases
Lead sponsor: 89bio, Inc.
Sponsor class: INDUSTRY
Collaborators: name: ProSciento, Inc.
First posted: 2019-08-07
Enrollment: 101
Sex: ALL
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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

Primary outcomes:
measure: Part 1: Number of Participants With Treatment-emergent Adverse Event (TEAEs)
timeFrame: Up to 113 days
measure: Part 2: Number of Participants With TEAEs
timeFrame: Up to 162 days
measure: Part 1: Maximum Observed Serum Concentration (Cmax) of Pegozafermin
timeFrame: Predose and up to 168 hours postdose on Day 29
measure: Part 1: Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Pegozafermin
timeFrame: Predose and up to 168 hours postdose on Day 29
measure: Part 1: Time to Peak Serum Concentration (Tmax) of Pegozafermin
timeFrame: Predose and up to 168 hours postdose on Day 29
measure: Part 1: Terminal Elimination Half-life (t1/2) of Pegozafermin
timeFrame: Predose and up to 168 hours postdose on Day 29
measure: 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
timeFrame: Day 141
Secondary outcomes:
measure: Part 1: Number of Participants With a Positive Anti-Drug Antibodies (ADA) Response to Pegozafermin
timeFrame: Up to 113 days
measure: Parts 1 and 2: Percent Change From Baseline in Body Weight
timeFrame: Part 1: Baseline, Day 85; Part 2: Baseline, Day 141
measure: 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)
timeFrame: Part 1: Baseline, Day 92; Part 2: Baseline, Day 141
measure: Part 1: Percent Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Day 92
timeFrame: Baseline, Day 92
measure: Part 1: Percent Change From Baseline in Adiponectin at Day 92
timeFrame: Baseline, Day 92
measure: Part 1: Percent Change From Baseline in Free Fatty Acid at Day 92
timeFrame: Baseline, Day 92
measure: Part 1: Percent Change From Baseline in Adipose Tissue Insulin Resistance (Adipo-IR) at Day 50
timeFrame: Baseline, Day 50
measure: Parts 1 and 2: Percent Change From Baseline in Liver Fat as Assessed Via Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)
timeFrame: Part 1: Baseline, Day 92; Part 2: Baseline, Day 141
measure: Part 2: Number of Participants With at Least an Improvement of Fibrosis ≥1 Stage Without Worsening of NASH
timeFrame: Day 141
measure: Part 2: Number of Participants With NASH Resolution Without Worsening of Fibrosis
timeFrame: Day 141
Other outcomes:
Locations:
city: Madison
country: United States
facility: 89bio Clinical Study Site
state: Alabama
city: Chandler
country: United States
facility: 89bio Clinical Study Site
state: Arizona
city: Tucson
country: United States
facility: 89bio Clinical Study Site
state: Arizona
city: Chula Vista
country: United States
facility: 89bio Clinical Study Site
state: California
city: Huntington Beach
country: United States
facility: 89bio Clinical Study Site
state: California
city: Montclair
country: United States
facility: 89bio Clinical Study Site
state: California
city: Miami Lakes
country: United States
facility: 89bio Clinical Study Site
state: Florida
city: Miami
country: United States
facility: 89bio Clinical Study Site
state: Florida
city: Ocala
country: United States
facility: 89bio Clinical Study Site
state: Florida
city: Sarasota
country: United States
facility: 89bio Clinical Study Site
state: Florida
city: Lake Charles
country: United States
facility: 89bio Clinical Study Site
state: Louisiana
city: Berlin
country: United States
facility: 89bio Clinical Study Site
state: New Jersey
city: Florham Park
country: United States
facility: 89bio Clinical Study Site
state: New Jersey
city: East Syracuse
country: United States
facility: 89bio Clinical Study Site
state: New York
city: Concord
country: United States
facility: 89bio Clinical Study Site
state: North Carolina
city: Raleigh
country: United States
facility: 89bio Clinical Study Site
state: North Carolina
city: Greenwood
country: United States
facility: 89bio Clinical Study Site
state: South Carolina
city: Summerville
country: United States
facility: 89bio Clinical Study Site
state: South Carolina
city: Hermitage
country: United States
facility: 89bio Clinical Study Site
state: Tennessee
city: Austin
country: United States
facility: 89bio Clinical Study Site
state: Texas
city: Edinburg
country: United States
facility: 89bio Clinical Study Site
state: Texas
city: Houston
country: United States
facility: 89bio Clinical Study Site
state: Texas
city: San Antonio
country: United States
facility: 89bio Clinical Study Site
state: Texas
city: San Antonio
country: United States
facility: 89bio Clinical Study Site
state: Texas
city: Wichita Falls
country: United States
facility: 89bio Clinical Study Site
state: Texas
city: San Juan
country: Puerto Rico
facility: 89bio Clinical Study Site
Study officials:
affiliation: 89bio, Inc.
name: Charlton, MD
role: STUDY_DIRECTOR
References: