Study Evaluating the Safety, Efficacy and Tolerability of BIO89-100 in Subjects With Biopsy-confirmed Nonalcoholic Steatohepatitis (NASH)

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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NASH - Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: BIO89-100


Participation Criteria
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Eligibility Criteria
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Key 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 Key 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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIO89-100 - 15 mg QW<br> | Drug: BIO89-100<br>* Subcutaneous injection<br>|
| Experimental: Experimental: BIO89-100 - 30 mg QW<br> | Drug: BIO89-100<br>* Subcutaneous injection<br>|
| Experimental: Experimental: BIO89-100 - 44 mg Q2W<br> | Drug: BIO89-100<br>* Subcutaneous injection<br>|
| Placebo Comparator: Placebo Comparator: Placebo QW<br> | Drug: BIO89-100<br>* Subcutaneous injection<br>|
| Placebo Comparator: Placebo Comparator: Placebo Q2W<br> | Drug: BIO89-100<br>* Subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Main: Proportion of participants with histological resolution of NASH without worsening of fibrosis |  | 24 Weeks | 
| Main: Proportion of participants with ≥1 stage decrease in fibrosis stage with no worsening of NASH |  | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Main: Proportion of participants with at least a 2-point improvement in NAS and no worsening of fibrosis |  | 24 Weeks | 
| Main: Proportion of participants with NASH resolution AND with ≥1 stage decrease in fibrosis stage |  | 24 Weeks | 
| Main: Proportion of participants with at least a 2-point improvement in NAS and are MRI-PDFF responders AND ALT responders |  | 24 Weeks | 
| Main: Absolute and percentage change from baseline in serum triglycerides |  | 12 Weeks, 24 Weeks | 
| Main: Absolute and percentage change from baseline in Low Density Lipoprotein (LDL) Cholesterol |  | 12 Weeks, 24 Weeks | 
| Main: Absolute change and percentage change from baseline in Alanine Transaminase (ALT) |  | 12 Weeks, 24 Weeks, 48 Weeks | 
| Main: Absolute change and percentage change from baseline in N-terminal type III collagen propeptide (Pro-C3) |  | 12 Weeks, 24 Weeks, 48 Weeks | 
| Main: Absolute change and percentage change from baseline in Magnetic Resonance Imaging - Hepatic Fat Fraction (MRI-PDFF) |  | 12 Weeks, 24 Weeks, 48 Weeks | 
| Main: Percentage change from baseline in HbA1c |  | 12 Weeks, 24 Weeks | 
| Main: Absolute and percentage change from baseline in Adiponectin |  | 12 Weeks, 24 Weeks | 
| Main: Steady-state blood level of BIO89-100 | Plasma trough concentration (ng/mL) of BIO89-100 taken at pre-dose samples | Blood samples for PK analysis collected at up to 8 study visits over the course of approximately 48 weeks | 
| Main: Absolute and percentage change from baseline in Non High Density Lipoprotein (HDL) Cholesterol |  | 12 Weeks, 24 Weeks | 
| Main: Absolute and percentage change from baseline in High Density Lipoprotein (HDL) Cholesterol |  | 12 Weeks, 24 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver Diseases, Fatty Liver, Digestive System Diseases, Non-alcoholic Fatty Liver Disease, Metabolic diseases, NASH NAFLD