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

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

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.

Study Overview

• Status: Terminated
• Conditions: Nonalcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: BMS-963272; Other: Placebo matching BMS-963272

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Cullman, Alabama, United States, 35055
      • Cullman Clinical Trials
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Local Institution
    • Tucson, Arizona, United States, 85712
      • Arizona Liver Health - Tucson
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Local Institution
    • Boynton Beach, Florida, United States, 33472
      • RecioMed Clinical Research Network
    • Miami, Florida, United States, 33014
      • Local Institution
    • Miami, Florida, United States, 33147
      • Advanced Pharma - Miami
    • Miami Lakes, Florida, United States, 33016
      • Floridian Clinical Research
    • Port Orange, Florida, United States, 32127
      • Local Institution
  • Louisiana
    • Bastrop, Louisiana, United States, 71220
      • Local Institution
  • Mississippi
    • Biloxi, Mississippi, United States, 39532
      • Local Institution
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Local Institution
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Local Institution
    • Germantown, Tennessee, United States, 38138
      • Local Institution
  • Texas
    • Austin, Texas, United States, 78757
      • Pinnacle Clinical Research - Austin
    • Edinburg, Texas, United States, 78539
      • Local Institution
    • McAllen, Texas, United States, 78504
      • Local Institution
    • San Antonio, Texas, United States, 78229
      • Local Institution
    • San Antonio, Texas, United States, 78215
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2021
• Primary Completion (Actual): August 12, 2021
• Study Completion (Actual): August 12, 2021

Study Registration Dates

• First Submitted: February 19, 2021
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 23, 2021

Study Record Updates

• Last Update Posted (Actual): June 9, 2022
• Last Update Submitted That Met QC Criteria: June 8, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Phase 1b; Liver Fibrosis; Nonalcoholic Steatohepatitis (NASH); BMS-963272; Nonalcoholic Fatty Liver Disease (NAFLD)
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: MB006-025

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No