Companion Protocol for ¹³C-Methacetin Breath Tests in BMS: NCT03486899, NCT03486912 Referenced Trials

NCT03611101 | Completed Results DMC

• 1 other identifier: BMS-EX-0118
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief Summary

This is a companion study assessing the ¹³C-Methacetin Breath Test (MBT) in subjects participating in the Bristol Myers-Squibb (BMS) NCT03486899 and NCT03486912 referenced studies using study drug BMS-986036.

Conditions

NASH - Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Percent Change in MBT From Day 1 to Week 48

  Identification of subjects that experience a change in metabolic capacity in each of the treatment arms versus placebo arm after 48 weeks compared to baseline as determined independently by the Methacetin Breath Test (MBT) PDR peak output parameter under a responder analysis. No actual cut-off values or specific values of percent change criteria were pre-specified since this study was solely exploratory by nature as described in the protocol. The MBT PDR peak parameter was collected and analyzed for all those that performed the MBT based on the initial eligibility criteria of the study protocol and obtained a valid device printout with a PDR peak result, with no other methods or criteria used to exclude subjects. The outcome measure PDR peak is automatically calculated and generated in the printout when the device completes its measuring.

  48 weeks

Secondary Outcomes (8)

• Number of Subjects That Experience Deterioration Events

  48 weeks

• Correlation

  48 weeks

• Correlation

  48 weeks

• Correlation

  48 weeks

• Correlation

  48 weeks

Study Arms (4)

BMS-986036 Dose Level 1

EXPERIMENTAL

Administered by subcutaneous injection

Combination Product: ¹³C-Methacetin Breath Test; Drug: BMS-986036; Device: BreathID MCS device

BMS-986036 Dose Level 2

EXPERIMENTAL

Administered by subcutaneous injection

Combination Product: ¹³C-Methacetin Breath Test; Drug: BMS-986036; Device: BreathID MCS device

BMS-986036 Dose Level 3

EXPERIMENTAL

Administered by subcutaneous injection

Combination Product: ¹³C-Methacetin Breath Test; Drug: BMS-986036; Device: BreathID MCS device

Placebo

PLACEBO COMPARATOR

Administered by subcutaneous injection

Combination Product: ¹³C-Methacetin Breath Test; Drug: BMS-986036; Device: BreathID MCS device

Interventions

¹³C-Methacetin Breath Test COMBINATION_PRODUCT

A breath analyzer will be used to measure changes in 12C (carbon 12) to 13C (carbon 13) ratio as a result of metabolism of the Methacetin substrate before and after treatment.

BMS-986036 Dose Level 1; BMS-986036 Dose Level 2; BMS-986036 Dose Level 3; Placebo

BMS-986036 DRUG

Investigational drug for NASH treatment in Main BMS protocol

BMS-986036 Dose Level 1; BMS-986036 Dose Level 2; BMS-986036 Dose Level 3; Placebo

BreathID MCS device DEVICE

The BreathID MCS device is a breath analyzer specifically used for measuring changes in the ratio of 13CO2 and 12CO2 isotopes of carbon dioxide. The device is connected to the subject via a nasal cannula and breath is passively collected before and after ingestion of labelled 13C- Methacetin substrate.

BMS-986036 Dose Level 1; BMS-986036 Dose Level 2; BMS-986036 Dose Level 3; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Liver biopsy performed within 6 months prior to the Screening Visit; if not performed within 6 months prior to the Screening Visit, a liver biopsy will be performed during the Screening Period and at least 4 weeks prior to randomization (Biopsy must be consistent with NASH, with: a) A score of at least 1 for each NAS component (steatosis, lobular inflammation, and ballooning), as assessed by the central reader AND b) Stage 3/Stage 4 (Cirrhosis) liver fibrosis (cohort 1 and cohort 2 respectively) according to the NASH CRN (Clinical Research Network) classification, as assessed by the central reader
• Participants taking anti-diabetic, anti-obesity, or anti-dyslipidemic medications must have been on stable dosing regimens for at least 3 months prior to the Screening Visit
• Participants taking vitamin E at doses ≥800 IU/day must have been on stable doses for at least 6 months prior to the Screening Visit (Vitamin E treatment must not have been initiated after the liver biopsy was performed)-

You may not qualify if:

• Other causes of liver disease (e.g., alcoholic liver disease, hepatitis B virus infection, chronic hepatitis C virus infection, autoimmune hepatitis, drug-induced hepatotoxicity, Wilson disease, alpha-1-antitrypsin deficiency, iron overload, and hemochromatosis)
• Current or past history of hepatocellular carcinoma (HCC)

Sponsors & Collaborators

• Meridian Bioscience, Inc.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Spring Gastroenterology

Humble, Texas, 77338-4125, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Pegbelfermin

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Limitations and Caveats

This companion protocol, evaluating the utility of the MBT as a biomarker for assessment of treatment efficacy of the parent study drug, was designed to be exploratory by nature, and no pre-specified criteria for success were set a priori. The parent study conclusion was that the study drug is ineffective based on several standard clinically used biomarkers. As such, evaluating MBT as a biomarker of drug efficacy for a drug that was shown not to be effective is not applicable.

Results Point of Contact

• Title: Clinical Trial Manager
• Organization: Exalenz Bioscience

avrahamh@exalenz.com

+972-8-9737513

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The collaborator is responsible for the masking process.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be enrolled and randomized via interactive response technology (IRT) to receive BMS-9860936 Dose Level 1 , BMS-986036 Dose Level 2, BMS-9860936 Dose Level 3 or matching placebo in a 1:1:1:1 ratio. in both Stage 3 liver fibrosis and cirrhosis cohorts.

Study Record Dates

• First Submitted: July 19, 2018
• First Posted: August 2, 2018
• Study Start: May 4, 2018
• Primary Completion: August 18, 2020
• Study Completion: November 10, 2021
• Last Updated: December 20, 2022
• Results First Posted: August 9, 2022

Record last verified: 2022-12

Locations

US (1)