Back to resultsCompanion Protocol for ¹³C-Methacetin Breath Tests in BMS: NCT03486899, NCT03486912 Referenced Trials
Primary Purpose
NASH - Nonalcoholic Steatohepatitis
Status
Completed
Phase
Locations
United States
Study Type
Interventional
Intervention
¹³C-Methacetin Breath Test
BMS-986036
BreathID MCS device
Sponsored by
About this trial
This is an interventional diagnostic trial for NASH - Nonalcoholic Steatohepatitis
Eligibility Criteria
Inclusion Criteria:
- 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)-
Exclusion Criteria:
- 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)
- Past or current evidence of hepatic decompensation (e.g., ascites, variceal bleeding, hepatic encephalopathy and/or spontaneous bacterial peritonitis) or liver transplantation Other protocol defined inclusion/exclusion criteria could apply
Sites / Locations
- Spring Gastroenterology
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
BMS-986036 Dose Level 1
BMS-986036 Dose Level 2
BMS-986036 Dose Level 3
Placebo
Arm Description
Administered by subcutaneous injection
Administered by subcutaneous injection
Administered by subcutaneous injection
Administered by subcutaneous injection
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Number of Subjects That Experience Deterioration Events
Binary diagnosis of subjects that experience deterioration event as determined by the MBT compared to the placebo treatment arm
Correlation
Correlation of MBT PDR Peak to biopsy proven changes in fibrosis and/or NAS (NAFLD Activity Score) from Day 1 to Week 48. Total NAS score represents the sum of scores for steatosis (0-3), lobular inflammation (0-3), and ballooning (0-2), and ranges from 0-8; where 8 is the most severe.
Correlation
Correlation of MBT changes to changes in liver stiffness as measured by Magnetic Resonance Elastography (MRE) from Day 1 to Week 48
Correlation
Correlation of MBT changes to changes in Proton Density Fat Fraction (PDFF) as measured by Magnetic Resonance Imaging(MRI) from Day 1 to Week 48
Correlation
Correlation of MBT changes to changes in Serum Pro-C3 results from Day 1 to Week 48
Correlation
Correlation of MBT changes to changes in liver elastography by Fibroscan (in cohort 2 only) from Day 1 to Week 48
Correlation
Correlation of MBT changes to changes in MELD (model for end-stage liver disease) scores (in cohort 2 only) from Day 1 to Week 48.The MELD score is generally calculated as: MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43. The higher the score, the more chances of mortality.
Correlation
Correlation of MBT changes to changes in CTP (Child-Turcotte-Pugh) score form Day 1 to Week 48. The CTP score is based on the sum of the ranges of the following parameters: total bilirubin (1-3), serum albumin (1-3), prothrombin time (1-3), ascites level (1-3) and hepatic encephalopathy grade (1-3). The higher the score, the more advanced is the liver disease
Full Information
NCT ID
NCT03611101
First Posted
July 19, 2018
Last Updated
December 19, 2022
Sponsor
Meridian Bioscience, Inc.
Collaborators
Bristol-Myers Squibb
1. Study Identification
Unique Protocol Identification Number
NCT03611101
Brief Title
Companion Protocol for ¹³C-Methacetin Breath Tests in BMS: NCT03486899, NCT03486912 Referenced Trials
Official Title
Companion Protocol for the ¹³C-Methacetin Breath Test (MBT) for Use in Bristol-Myers Squibb Phase 2b Studies for BMS-986036 (PEG-FGF21), Under Studies Referenced in NCT03486899, NCT03486912
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
May 4, 2018 (Actual)
Primary Completion Date
August 18, 2020 (Actual)
Study Completion Date
November 10, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Meridian Bioscience, Inc.
Collaborators
Bristol-Myers Squibb
4. Oversight
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
Subjects that are enrolled into either of two separate BMS sponsored IND (Investigational New Drug) studies (referenced by NCT03486899 and NCT03486912) at selected study sites will be offered the opportunity to perform the MBT. These will be considered as two separate study cohorts (cohort 1 and 2 respectively) within this companion protocol. There are four (4) treatment arms (BMS-986036 Dose Level 1, Dose Level 2, Dose Level 3 or matching placebo), as defined in the respective BMS sponsored protocols.
Cohort 1 consists of Subjects with NASH and stage 3 fibrosis, as assessed by a central laboratory reader of the liver biopsies (up to 160), and who meet all the NCT03486899 referenced study criteria.
Cohort 2 consists of Subjects with NASH and compensated liver cirrhosis, as assessed by a central laboratory reader of the liver biopsies (up to100), and who meet all the NCT03486912 referenced study criteria.
Approximately 75 sites will be included in the BMS studies, but not all participating sites will elect to perform the MBT. Each subject will perform up to 3 MBTs over 1 year; approximately one every 24 weeks.
The MBT in this study will only be conducted in the USA.
The primary purpose of the BMS study is to assess an experimental treatment for the following conditions: Hepatic cirrhosis, liver fibrosis, Nonalcoholic Fatty Liver Disease (NAFLD) and NASH (Nonalcoholic Steatohepatitis).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NASH - Nonalcoholic Steatohepatitis
7. Study Design
Primary Purpose
Diagnostic
Interventional Study Model
Parallel Assignment
Model Description
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The collaborator is responsible for the masking process.
Allocation
Randomized
Enrollment
124 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BMS-986036 Dose Level 1
Arm Type
Experimental
Arm Description
Administered by subcutaneous injection
Arm Title
BMS-986036 Dose Level 2
Arm Type
Experimental
Arm Description
Administered by subcutaneous injection
Arm Title
BMS-986036 Dose Level 3
Arm Type
Experimental
Arm Description
Administered by subcutaneous injection
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Administered by subcutaneous injection
Intervention Type
Combination Product
Intervention Name(s)
¹³C-Methacetin Breath Test
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
BMS-986036
Intervention Description
Investigational drug for NASH treatment in Main BMS protocol
Intervention Type
Device
Intervention Name(s)
BreathID MCS device
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percent Change in MBT From Day 1 to Week 48
Description
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.
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Number of Subjects That Experience Deterioration Events
Description
Binary diagnosis of subjects that experience deterioration event as determined by the MBT compared to the placebo treatment arm
Time Frame
48 weeks
Title
Correlation
Description
Correlation of MBT PDR Peak to biopsy proven changes in fibrosis and/or NAS (NAFLD Activity Score) from Day 1 to Week 48. Total NAS score represents the sum of scores for steatosis (0-3), lobular inflammation (0-3), and ballooning (0-2), and ranges from 0-8; where 8 is the most severe.
Time Frame
48 weeks
Title
Correlation
Description
Correlation of MBT changes to changes in liver stiffness as measured by Magnetic Resonance Elastography (MRE) from Day 1 to Week 48
Time Frame
48 weeks
Title
Correlation
Description
Correlation of MBT changes to changes in Proton Density Fat Fraction (PDFF) as measured by Magnetic Resonance Imaging(MRI) from Day 1 to Week 48
Time Frame
48 weeks
Title
Correlation
Description
Correlation of MBT changes to changes in Serum Pro-C3 results from Day 1 to Week 48
Time Frame
48 weeks
Title
Correlation
Description
Correlation of MBT changes to changes in liver elastography by Fibroscan (in cohort 2 only) from Day 1 to Week 48
Time Frame
48 weeks
Title
Correlation
Description
Correlation of MBT changes to changes in MELD (model for end-stage liver disease) scores (in cohort 2 only) from Day 1 to Week 48.The MELD score is generally calculated as: MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43. The higher the score, the more chances of mortality.
Time Frame
48 weeks
Title
Correlation
Description
Correlation of MBT changes to changes in CTP (Child-Turcotte-Pugh) score form Day 1 to Week 48. The CTP score is based on the sum of the ranges of the following parameters: total bilirubin (1-3), serum albumin (1-3), prothrombin time (1-3), ascites level (1-3) and hepatic encephalopathy grade (1-3). The higher the score, the more advanced is the liver disease
Time Frame
48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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)-
Exclusion Criteria:
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)
Past or current evidence of hepatic decompensation (e.g., ascites, variceal bleeding, hepatic encephalopathy and/or spontaneous bacterial peritonitis) or liver transplantation Other protocol defined inclusion/exclusion criteria could apply
Facility Information:
Facility Name
Spring Gastroenterology
City
Humble
State/Province
Texas
ZIP/Postal Code
77338-4125
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Companion Protocol for ¹³C-Methacetin Breath Tests in BMS: NCT03486899, NCT03486912 Referenced Trials
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