A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of BIO89-100 in Subjects With Biopsy-Confirmed Nonalcoholic Steatohepatitis (NASH)
Overview
- Phase
- Phase 2
- Intervention
- BIO89-100
- Conditions
- NASH - Nonalcoholic Steatohepatitis
- Sponsor
- 89bio, Inc.
- Enrollment
- 222
- Locations
- 89
- Primary Endpoint
- Main Study: Number of Participants With Histological Resolution of Nonalcoholic Steatohepatitis (NASH) Without Worsening of Fibrosis
- Status
- Completed
- Last Updated
- 3 months ago
Overview
Brief Summary
This is a randomized, double-blind, placebo-controlled study that will evaluate the safety, efficacy, tolerability of BIO89-100 in patients with biopsy-confirmed fibrosis stages F2-F3 NASH.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 21 to 75
- •Biopsy-confirmed NASH with fibrosis stage F2 or F3 per NASH CRN System and NAS ≥4, with a score of at least 1 in each of steatosis, ballooning degeneration, and lobular inflammation.
- •Qualifying biopsy must be either within 6 months of screening visit or obtained during screening period
Exclusion Criteria
- •Have poorly controlled high blood pressure
- •Have type 1 diabetes or poorly controlled type 2 diabetes.
- •History of cirrhosis or evidence of cirrhosis by clinical, imaging, or liver biopsy evaluation
- •Are planning to try to lose weight during the conduct of the study.
- •Have a BMI \<25 kg/m2
- •Other inclusion and exclusion criteria may apply.
Arms & Interventions
BIO89-100 - 15 mg once weekly (QW)
Intervention: BIO89-100
BIO89-100 - 30 mg QW
Intervention: BIO89-100
BIO89-100 - 44 mg once every 2 weeks (Q2W)
Intervention: BIO89-100
Placebo QW
Intervention: Placebo
Placebo Q2W
Intervention: Placebo
Placebo QW (Main study)/ BIO89-100 - 30 mg QW (Extension)
Intervention: BIO89-100
Placebo QW (Main study)/ BIO89-100 - 30 mg QW (Extension)
Intervention: Placebo
Outcomes
Primary Outcomes
Main Study: Number of Participants With Histological Resolution of Nonalcoholic Steatohepatitis (NASH) Without Worsening of Fibrosis
Time Frame: Week 24
Nonalcoholic fatty liver disease activity score (NAS) was the sum of the scores of steatosis, inflammation, and ballooning. NAS score ranged from 0 to 8, with higher scores indicating worse disease severity. Resolution of NASH was defined as the total absence of ballooning (score=0) and absent or mild inflammation (score=0 to 1). NASH clinical research system (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). Worsening of fibrosis was defined as progression of fibrosis greater than or equal to (≥) 1 stage in NASH CRN fibrosis score.
Main Study: Number of Participants Who Achieved Improvement of Fibrosis ≥1 Stage Without Worsening of NASH
Time Frame: Week 24
Worsening of NASH was defined as increase in nonalcoholic fatty liver disease activity score (NAS) for ballooning, inflammation, or steatosis. NAS was the sum of the scores of steatosis, inflammation, and ballooning. NAS score ranged from 0 to 8, with higher scores indicating worse disease severity. Fibrosis improvement was defined as ≥1-stage decrease 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).
Secondary Outcomes
- Main Study: Number of Participants With at Least a 2-Point Improvement in NAS and no Worsening of Fibrosis(Week 24)
- Main Study: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-c)(Baseline, Week 24)
- Main Study: Number of Participants With NASH Resolution and Fibrosis Improvement ≥1 Stage(Week 24)
- Main Study: Number of Participants With at Least a 2-point Improvement in NAS Score and Are Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) Responders and Alanine Aminotransferase (ALT) Responders(Week 24)
- Main Study: Percent Change From Baseline in Serum Triglycerides(Baseline, Week 24)
- Main Study: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-c)(Baseline, Week 24)
- Main Study: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-c)(Baseline, Week 24)
- Main Study: Percent Change From Baseline in Adiponectin(Baseline, Week 24)
- Main Study: Percent Change From Baseline in HbA1c (Glycated Hemoglobin)(Baseline, Week 24)
- Main Study: Percent Change From Baseline in Alanine Transaminase(Baseline, Week 12 and 24)
- Main Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF)(Baseline, Week 12 and 24)
- Main Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3)(Baseline, Week 12 and 24)
- Main Study: Trough Serum Concentration of Pegozafermin(Predose at Week 12 and 24)
- Main and Extension Study: Percent Change From Baseline in Alanine Transaminase(Baseline, Week 48)
- Main and Extension Study: Percent Change From Baseline in N-Terminal Type III Collagen Propeptide (Pro-C3)(Baseline, Week 48)
- Main and Extension Study: Percent Change From Baseline in Hepatic Fat Fraction By Magnetic Resonance Imaging - (MRI-PDFF)(Baseline, Week 48)
- Main and Extension Study: Trough Serum Concentration of Pegozafermin(Predose at Week 48)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Baseline up to Week 51)