A Study to Evaluate the Safety, Tolerability, and Drug Levels of BMS-963272 in Participants With Nonalcoholic Fatty Liver Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, and drug levels of BMS-963272 compared to placebo in participants with nonalcoholic fatty liver disease (NAFLD) and high probability of advanced fibrosis.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 1b Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BMS-963272 in Participants With Nonalcoholic Fatty Liver Disease

Conditions
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Nonalcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: BMS-963272
* Other: Placebo matching BMS-963272


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) ≥ 30 kg/m^2 Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 10% as evaluated by central review FibroScan-based transient elastography ≥ 9.9 kPa Alanine aminotransferase (ALT): > 30 U/L If available, historical diagnosis of non-alcoholic steatohepatitis (NASH) according to NASH Clinical Research Network classification by liver biopsy within 6 months before screening will be recorded Must agree to follow specific methods of contraception, if applicable Exclusion Criteria: Women who are breastfeeding Inability to tolerate the mixed meal or the testing conditions, oral medication, venipuncture and/or inadequate venous access History or current diagnosis of cirrhosis, hepatocellular carcinoma (HCC), or hepatic decompensation Recent history (within 2 years before screening) of drug or alcohol abuse or excessive alcohol intake, defined as 30 g/day (men) or 20 g/day (women) Use of lipase inhibitors such as orlistat within 4 weeks before screening or during screening Use of glucagon-like peptide-1 (GLP-1) receptor agonists within 12 weeks before screening or during screening Uncontrolled hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg) during screening, unless discussed with the Medical Monitor Glycated hemoglobin (HbA1c) ≥ 9.5% NASH-modifying therapies including investigational therapies (e.g., obeticholic acid, ursodeoxycholic acid) within 90 days before screening or during screening Medications for obesity within 12 weeks before screening, or during screening If taking vitamin E at a dose ≥ 800 mg/day, the dose must be stable beginning at least 6 months before screening and should remain stable during screening If taking a thiazolidinedione, the dose must be stable beginning at least 12 weeks before screening and should remain stable during screening If taking a dipeptidyl peptidase (DPP)-4 inhibitor or other medications for diabetes, the dose must be stable beginning at least 12 weeks before screening and should remain stable during screening If taking insulin, the dose may be altered by up to 10% within 12 weeks before screening and during the screening period If taking a statin or other prescription or over-the-counter lipid-lowering drug, the dose must be stable beginning at least 6 weeks before screening and should remain stable during screening Other protocol-defined inclusion/exclusion criteria apply

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Treatment (BMS-963272) Dosing Regimen 1<br> | Drug: BMS-963272<br>* Specified dose on specified days<br>|
| Experimental: Active Treatment (BMS-963272) Dosing Regimen 2<br> | Drug: BMS-963272<br>* Specified dose on specified days<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo matching BMS-963272<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) |  | Up to 166 days | 
| Incidence of serious adverse events (SAEs) |  | Up to 166 days | 
| Incidence of clinically significant changes in vital signs: Blood pressure |  | Up to 166 days | 
| Incidence of clinically significant changes in vital signs: Heart rate |  | Up to 166 days | 
| Incidence of clinically significant changes in physical examination findings |  | Up to 166 days | 
| Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval | PR interval: The time from the onset of the P wave to the start of the QRS complex | Up to 166 days | 
| Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS interval | QRS interval: A combination of the Q wave, R wave and S wave, the QRS complex represents ventricular depolarization | Up to 166 days | 
| Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval | QT interval: Measured from the beginning of the QRS complex to the end of the T wave | Up to 166 days | 
| Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF interval | QTcF interval: Corrected QT interval using Fridericia's formula (QTcF) | Up to 166 days | 
| Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry test |  | Up to 166 days | 
| Incidence of clinically significant changes in clinical laboratory results: Hematology tests |  | Up to 166 days | 
| Incidence of clinically significant changes in clinical laboratory results: Coagulation tests |  | Up to 166 days | 
| Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests |  | Up to 46 days | 
| Incidence of clinically significant changes in clinical laboratory results: Liver function tests |  | Up to 166 days | 
| Incidence of clinically significant changes in clinical laboratory results: Lipid panel tests |  | Up to 166 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) sampling: Maximum observed plasma concentration (Cmax) |  | Day 1 and Day 84 | 
| Pharmacokinetic (PK) sampling: Time to maximum observed plasma concentration (Tmax) |  | Day 1 and Day 84 | 
| Pharmacokinetic (PK) sampling: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC [0-T]) |  | Day 1 and Day 84 | 
| Trough observed plasma concentration (Ctrough) |  | Day 1, Day 15, Day 29, Day 57, and Day 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BMS-963272, Liver Fibrosis, Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH), Phase 1b