NASH - Nonalcoholic SteatohepatitisNCT03611101
Companion Protocol for ¹³C-Methacetin Breath Tests in BMS: NCT03486899, NCT03486912 Referenced Trials
A study testing ¹³C-Methacetin Breath Test, BMS-986036 and BreathID MCS device in people with NASH - Nonalcoholic Steatohepatitis, run by Meridian Bioscience, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- NASH - Nonalcoholic Steatohepatitis
- What is being tested?
- ¹³C-Methacetin Breath Test, BMS-986036 and BreathID MCS device
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 124 participants
- Where
- 1 siteUnited States
- Study dates
- 4 May 2018to 10 Nov 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)-
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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).
- Conditions
- NASH - Nonalcoholic Steatohepatitis
- Being tested
- ¹³C-Methacetin Breath Test, BMS-986036, BreathID MCS device
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
¹³C-Methacetin Breath TestCombination 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-986036Drug
Investigational drug for NASH treatment in Main BMS protocol
BreathID MCS deviceDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| BMS-986036 Dose Level 1 | Experimental | Administered by subcutaneous injection Receives: Combination Product: ¹³C-Methacetin Breath Test; Drug: BMS-986036; Device: BreathID MCS device |
| BMS-986036 Dose Level 2 | Experimental | Administered by subcutaneous injection Receives: Combination Product: ¹³C-Methacetin Breath Test; Drug: BMS-986036; Device: BreathID MCS device |
| BMS-986036 Dose Level 3 | Experimental | Administered by subcutaneous injection Receives: Combination Product: ¹³C-Methacetin Breath Test; Drug: BMS-986036; Device: BreathID MCS device |
| Placebo | Placebo comparator | Administered by subcutaneous injection Receives: Combination Product: ¹³C-Methacetin Breath Test; Drug: BMS-986036; Device: BreathID MCS device |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 48 weeks
Secondary outcomes (8)
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
Measured: 48 weeks
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.
Measured: 48 weeks
Correlation
Correlation of MBT changes to changes in liver stiffness as measured by Magnetic Resonance Elastography (MRE) from Day 1 to Week 48
Measured: 48 weeks
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
Measured: 48 weeks
Correlation
Correlation of MBT changes to changes in Serum Pro-C3 results from Day 1 to Week 48
Measured: 48 weeks
Correlation
Correlation of MBT changes to changes in liver elastography by Fibroscan (in cohort 2 only) from Day 1 to Week 48
Measured: 48 weeks
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.
Measured: 48 weeks
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
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2018
- Study start4 May 2018
- Primary completion18 Aug 2020
- Study completion10 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for NASH - Nonalcoholic SteatohepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- Meridian Bioscience, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03611101
- Sponsor's protocol ID
- BMS-EX-0118
- Status last verified
- Dec 2022
- First submitted
- 19 Jul 2018
- Last updated
- 20 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03611101
- Acronym / sponsor ID
- BMS-EX-0118
- Conditions
- NASH - Nonalcoholic Steatohepatitis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 124 participants (actual)
- Lead sponsor
- Meridian Bioscience, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Study start
- 4 May 2018 (actual)
- Primary completion
- 18 Aug 2020 (actual)
- Study completion
- 10 Nov 2021 (actual)
- First posted
- 2 Aug 2018 (actual)
- Results
- Posted 9 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| BMS-986036 Dose Level 1 | Experimental | Combination Product: ¹³C-Methacetin Breath Test, Drug: BMS-986036, Device: BreathID MCS deviceAdministered by subcutaneous injection |
| BMS-986036 Dose Level 2 | Experimental | Combination Product: ¹³C-Methacetin Breath Test, Drug: BMS-986036, Device: BreathID MCS deviceAdministered by subcutaneous injection |
| BMS-986036 Dose Level 3 | Experimental | Combination Product: ¹³C-Methacetin Breath Test, Drug: BMS-986036, Device: BreathID MCS deviceAdministered by subcutaneous injection |
| Placebo | Placebo comparator | Combination Product: ¹³C-Methacetin Breath Test, Drug: BMS-986036, Device: BreathID MCS deviceAdministered by subcutaneous injection |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)-
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ¹³C-Methacetin Breath TestA 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. | Combination product | BMS-986036 Dose Level 1, BMS-986036 Dose Level 2, BMS-986036 Dose Level 3, Placebo |
| BMS-986036Investigational drug for NASH treatment in Main BMS protocol | Drug | BMS-986036 Dose Level 1, BMS-986036 Dose Level 2, BMS-986036 Dose Level 3, Placebo |
| BreathID MCS deviceThe 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. | Device | BMS-986036 Dose Level 1, BMS-986036 Dose Level 2, BMS-986036 Dose Level 3, Placebo |
Primary outcome
Percent Change in MBT From Day 1 to Week 48
Time frame: 48 weeks
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.
8 secondary outcomes
Number of Subjects That Experience Deterioration Events
Time frame: 48 weeks
Correlation
Time frame: 48 weeks
Correlation
Time frame: 48 weeks
Correlation
Time frame: 48 weeks
Correlation
Time frame: 48 weeks
Correlation
Time frame: 48 weeks
Correlation
Time frame: 48 weeks
Correlation
Time frame: 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for NASH - Nonalcoholic Steatohepatitis
RecruitingPhase 3
A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis
NASH With Fibrosis, MASH With Fibrosis
Active, not recruitingPhase 1/2
A Study to Evaluate ALN-CIDEB in Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease or With Metabolic Dysfunction-Associated Steatohepatitis (MASLD/MASH)
Metabolic Dysfunction-Associated Steatotic Liver Disease, Metabolic Dysfunction-Associated Steatohepatitis
Active, not recruiting
Target of Suv420h1/2 in Hepatocytes
NAFLD
Active, not recruitingPhase 3
A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 )
NASH - Nonalcoholic Steatohepatitis
Not yet recruitingPhase 2/3
Evaluating the Safety and Efficacy of Roflumilast in the Treatment of Nonalcoholic Fatty Liver Disease Patients
NAFLD (Nonalcoholic Fatty Liver Disease)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ¹³C-Methacetin Breath Test, BMS-986036 and BreathID MCS device in people with NASH - Nonalcoholic Steatohepatitis, run by Meridian Bioscience, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in MBT From Day 1 to Week 48 (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2022.