A Sub-study of BMS-986036 in Subjects With Non-Alcoholic Steatohepatitis (NASH)

Study Overview
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Brief Summary
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The purpose of this sub-study of MB130-045 is to determine the pharmacokinetic effects, pharmacodynamic effects, efficacy and safety of BMS-986036 20 mg QD in subjects with Non-alcoholic Steatohepatitis (NASH)

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multiple Dose Sub-study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamic Effects of BMS-986036 in Adults With Non-alcoholic Steatohepatitis

Conditions
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Non-Alcoholic Steatohepatitis

Intervention / Treatment
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* Drug: BMS-986036
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Male or female between 21 and 75 years old Body Mass Index (BMI) of 25 or more Exclusion Criteria: Chronic Liver disease other than NASH Uncontrolled diabetes Any major surgery within 6 weeks of screening Unable to self-administer under the skin injections Any bone trauma, fracture or bone surgery within 8 weeks of screening

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group D:<br>Administered as specified on specified days | Drug: BMS-986036<br>* BMS-986036 20 mg QD<br>|
| Placebo Comparator: Treatment Group E:<br>Administered as specified on specified days | Drug: Placebo<br>* Placebo QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Percent Hepatic Fat Fraction (%) by Magnetic Resonance Imaging (MRI) From Baseline to Week 16 | The mean change in percent hepatic fat fraction (%) by MRI from baseline to Week 16 was assessed for each arm. A longitudinal repeated measures analysis was used to analyze the change in hepatic fat fraction (%) at Week 16 from baseline in the treated population who have both a baseline and at least one post-baseline measurement. | From Day 1 to Day 112 | 
| Number of Participants With Adverse Events (AEs) | The number of participants with on-study AEs was reported for each arm. | From first dose to date of last dose plus 30 days | 
| Number of Participants With Serious Adverse Events (SAEs) | The number of participants with on-study SAEs was reported for each arm. | From first dose to date of last dose plus 30 days | 
| Number of Participants With Injection Site Reactions | The number of participants with on-study injection site reactions was reported for each arm. | From first dose to date of last dose plus 30 days | 
| Number of Participants With Adverse Events Leading to Discontinuation | The number of participants with on-study AEs leading to discontinuation was reported for each arm. | From first dose to date of last dose plus 30 days | 
| Number of Deaths | The number of deaths was reported for each arm. | From first dose to date of last dose plus 30 days | 
| Number of Participants With Marked Laboratory Abnormalities | The number of participants whose worst toxicity grade increased from baseline to grade 3 or 4 (Toxicity Scale: DAIDS Version 1.0) is reported for each arm. | From first dose to date of last dose plus 30 days | 
| Number of Participants With Vital Sign Abnormalities | The number of participants with out-of-range vital signs noted during interim or final vital sign assessments was reported for each arm. | From first dose to date of last dose plus 30 days | 
| Number of Participants With Electrocardiogram (ECG) Abnormalities | The number of participants with out-of-range ECG intervals observed during interim or final electrocardiogram assessments was reported for each arm. | From first dose to date of last dose plus 30 days | 
| Number of Participants With Physical Examination Abnormalities | The number of participants with abnormalities observed during interim or final physical examination assessments is reported for each arm. | From first dose to date of last dose plus 30 days | 
| Mean Percent Change From Baseline in Bone Mineral Density by Dual Energy X-Ray Absorptiometry (DXA) | The mean percent change in bone mineral density from baseline to day 112 reported for each arm. | From Day 1 to Day 112 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean of Trough Observed Plasma Concentration (Ctrough) of BMS-986036 at Day 112 | The observed serum concentration of BMS-986036 before the next dose is administered (pre-dose concentration) was assessed for both C-terminal intact and total molecule. Geometric means are presented for each arm. | From Day 1 to Day 112 | 
| Number of Participants With Positive Anti-BMS-986036 Antibody (ADA) Response at Day 142 | Participants were monitored for antibodies to study medication using a validated ADA homogenous bridge assay with BMS-986036 and electrochemical luminescence detection. The number of treated participants with positive Anti-BMS-986036 antibody titers up to Day 142 with regards to baseline was reported for each arm. | From Day 1 to Day 142 | 
| Number of Participants With Positive Anti-FGF21 Antibody Response at Day 142 | Participants were monitored for antibodies to FGF21 using a validated homogenous bridge assay with Met-FGF21 (recombinant produced) and electrochemical luminescence detection. The number of treated participants with positive Anti-FGF21 antibody titers up to Day 142 with regards to baseline was reported for each arm. | From Day 1 to Day 142 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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First Line Therapy, NASH