A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of BFKB8488A Compared With Placebo in Participants With Non-Alcoholic Steatohepatitis

Study Overview
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Brief Summary
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This study will evaluate the efficacy, safety, and pharmacokinetics of BFKB8488A compared to placebo in participants with non-alcoholic steatohepatitis (NASH).

Official Title
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A Phase II, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of BFKB8488A Compared With Placebo in Patients With Non-Alcoholic Steatohepatitis

Conditions
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Non-alcoholic Steatohepatitis

Intervention / Treatment
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* Drug: Placebo
* Drug: BFKB8488A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Confirmed diagnosis of NASH as documented through liver biopsy performed no more than 6 months before randomization, defined according to NASH CRN criteria along with a NASH CRN fibrosis score between F2 and F3 Hepatic steatosis on MRI (>= 8% average PDFF) prior to randomization Exclusion Criteria History of any liver disease other than NASH, except for resolved, self-limited illnesses such as Hepatitis A or E, and previous Hepatitis C Weight gain > 10% or loss > 5% within 3 months prior to randomization History of liver transplantation Current or history of significant alcohol consumption

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Fixed Dose: Placebo<br>Participants will receive a fixed dose of placebo matched to BFKB8488A. | Drug: Placebo<br>* Participants will receive subcutaneous (SC) placebo matched to BFKB8488A.<br>|
| Placebo Comparator: Individualized Dose: Placebo<br>Participants will received a dose of placebo matched to BFKB8488A. | Drug: Placebo<br>* Participants will receive subcutaneous (SC) placebo matched to BFKB8488A.<br>|
| Experimental: Fixed Dose: BFKB8488A Dose A<br>Participants will receive BFKB8488A. | Drug: BFKB8488A<br>* Participants will receive subcutaneous (SC) BFKB8488A.<br>|
| Experimental: Fixed Dose: BFKB8488A Dose B<br>Participants will receive BFKB8488A. | Drug: BFKB8488A<br>* Participants will receive subcutaneous (SC) BFKB8488A.<br>|
| Experimental: Fixed Dose: BFKB8488A Dose C<br>Participants will receive BFKB8488A. | Drug: BFKB8488A<br>* Participants will receive subcutaneous (SC) BFKB8488A.<br>|
| Experimental: Individualized Dose: BFKB8488A<br>Participants will receive increasing doses of BFKB8488A up to the highest tolerated dose . | Drug: BFKB8488A<br>* Participants will receive subcutaneous (SC) BFKB8488A.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants with NASH Resolution on Overall Histopathological Reading Without Worsening of Fibrosis at Week 52 |  | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Hepatic Fat Fraction as Assessed by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at Week 52 |  | Week 52 | 
| Proportion of Participants with Improvement in Liver Histology |  | Week 52 | 
| Proportion of Participants with Improvement in Liver Fibrosis of at Least One Stage, as Defined by NASH Clinical Research Network (CRN), and no Worsening of NASH at Week 52 |  | Week 52 | 
| Percentage of Participants with Adverse Events |  | Week 58 | 
| Serum Concentration of BFKB8488A |  | At pre-defined intervals from baseline to Week 58 | 
| Percentage of Participants with Anti-Drug Antibodies |  | Week 58 |