Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Bristol-Myers Squibb | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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).
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BMS-986036 Dose Level 1 | Experimental | Administered by subcutaneous injection |
|
| BMS-986036 Dose Level 2 | Experimental | Administered by subcutaneous injection |
|
| BMS-986036 Dose Level 3 | Experimental | Administered by subcutaneous injection |
|
| Placebo | Placebo Comparator | Administered by subcutaneous injection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 48 weeks |
| Correlation |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Spring Gastroenterology | Humble | Texas | 77338-4125 | United States |
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | BMS-986036 Dose Level 1 10 mg | Administered by subcutaneous injection ¹³C-Methacetin Breath Test: 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: Investigational drug for NASH treatment in Main BMS protocol BreathID MCS 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. |
| FG001 | BMS-986036 Dose Level 2 20 mg | Administered by subcutaneous injection ¹³C-Methacetin Breath Test: 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: Investigational drug for NASH treatment in Main BMS protocol BreathID MCS 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. |
| FG002 | BMS-986036 Dose Level 3 40 mg | Administered by subcutaneous injection ¹³C-Methacetin Breath Test: 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: Investigational drug for NASH treatment in Main BMS protocol BreathID MCS 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. |
| FG003 | Placebo | Administered by subcutaneous injection ¹³C-Methacetin Breath Test: 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: Investigational drug for NASH treatment in Main BMS protocol BreathID MCS 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
It should be noted, that there is no specific single outcome baseline measure, since the study compares each subject's baseline breath test results (PDR peak) to his/her future results to see if any changes were detected due to treatment. Every subject has a unique baseline. The actual measure is breath test PDR peak at Day 1. No analysis is done on the baseline measure , as it is only a reference for detecting changes.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | BMS-986036 Dose Level 1 10 mg | Administered by subcutaneous injection ¹³C-Methacetin Breath Test: 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: Investigational drug for NASH treatment in Main BMS protocol BreathID MCS 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Percent Change in PDR peak (MBT parameter) from Day 1 to Week 48 in the Safety Analysis Set (Intended to be treated). Due to COVID-19, a follow up MBT at Week 48 was partial and did not include all those that performed the initial MBT on Day 1.. | Posted | Mean | Standard Deviation | percentage of change in MBT | 48 weeks |
48 hours after Methacetin Breath Test
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BMS-986036 Dose Level 1 10 mg | Administered by subcutaneous injection ¹³C-Methacetin Breath Test: 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: Investigational drug for NASH treatment in Main BMS protocol BreathID MCS 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. |
Not provided
Not provided
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Manager | Exalenz Bioscience | +972-8-9737513 | avrahamh@exalenz.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 20, 2018 | Feb 28, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 5, 2021 | Feb 28, 2022 | SAP_001.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000630067 | Pegbelfermin |
Not provided
Not provided
Not provided
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.
Not provided
Not provided
The collaborator is responsible for the masking process.
| BMS-986036 | Drug | Investigational drug for NASH treatment in Main BMS protocol |
|
| 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. |
|
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.
| 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 | 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 | 48 weeks |
| Correlation | Correlation of MBT changes to changes in Serum Pro-C3 results from Day 1 to Week 48 | 48 weeks |
| Correlation | Correlation of MBT changes to changes in liver elastography by Fibroscan (in cohort 2 only) from Day 1 to Week 48 | 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. | 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 | 48 weeks |
| BG001 | BMS-986036 Dose Level 2 20 mg | Administered by subcutaneous injection ¹³C-Methacetin Breath Test: 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: Investigational drug for NASH treatment in Main BMS protocol BreathID MCS 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. |
| BG002 | BMS-986036 Dose Level 3 40 mg | Administered by subcutaneous injection ¹³C-Methacetin Breath Test: 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: Investigational drug for NASH treatment in Main BMS protocol BreathID MCS 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. |
| BG003 | Placebo | Administered by subcutaneous injection ¹³C-Methacetin Breath Test: 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: Investigational drug for NASH treatment in Main BMS protocol BreathID MCS 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. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID | Title | Description |
|---|
| OG000 | BMS-986036 Dose Level 1 10 mg | Administered by subcutaneous injection ¹³C-Methacetin Breath Test: 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: Investigational drug for NASH treatment in Main BMS protocol BreathID MCS 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. |
| OG001 | BMS-986036 Dose Level 2 20 mg | Administered by subcutaneous injection ¹³C-Methacetin Breath Test: 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: Investigational drug for NASH treatment in Main BMS protocol BreathID MCS 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. |
| OG002 | BMS-986036 Dose Level 3 40 mg | Administered by subcutaneous injection ¹³C-Methacetin Breath Test: 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: Investigational drug for NASH treatment in Main BMS protocol BreathID MCS 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. |
| OG003 | Placebo | Administered by subcutaneous injection ¹³C-Methacetin Breath Test: 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: Investigational drug for NASH treatment in Main BMS protocol BreathID MCS 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. |
|
|
| Secondary | 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 | Posted | Count of Participants | Participants | 48 weeks |
|
|
|
| Secondary | 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. | Posted | Number | r-correlation | 48 weeks |
|
|
|
| Secondary | Correlation | Correlation of MBT changes to changes in liver stiffness as measured by Magnetic Resonance Elastography (MRE) from Day 1 to Week 48 | Posted | Number | r-correlation | 48 weeks |
|
|
|
| Secondary | 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 | Posted | Number | r-correlation | 48 weeks |
|
|
|
| Secondary | Correlation | Correlation of MBT changes to changes in Serum Pro-C3 results from Day 1 to Week 48 | Posted | Number | r-correlation | 48 weeks |
|
|
|
| Secondary | Correlation | Correlation of MBT changes to changes in liver elastography by Fibroscan (in cohort 2 only) from Day 1 to Week 48 | Posted | Number | r-correlation | 48 weeks |
|
|
|
| Secondary | 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. | The objective of this endpoint was to compare changes in MBT collected for all subjects versus changes in MELD, a clinically used parameter used to assess liver function in each arm, over the course of the participation time in this trial, The result value is N/A if there were no subjects that had a MELD value that changed over the course of the trial, rendering r-correlation evaluation of changes in MBT versus changes in MELD not applicable. | Posted | Number | r-correlation | 48 weeks |
|
|
|
| Secondary | 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 | The objective of this endpoint was to compare changes in MBT collected for all subjects versus changes in CTP, a clinically used parameter used to assess liver function, in each arm, over the course of the participation time in this trial, The result value is N/A if there were no subjects that had a CTP value that changed over the course of the trial, rendering r-correlation evaluation of changes in MBT versus changes in CTP not applicable. | Posted | Number | r-correlation | 48 weeks |
|
|
|
| 0 |
| 32 |
| 0 |
| 32 |
| 0 |
| 32 |
| EG001 | BMS-986036 Dose Level 2 20 mg | Administered by subcutaneous injection ¹³C-Methacetin Breath Test: 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: Investigational drug for NASH treatment in Main BMS protocol BreathID MCS 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. | 0 | 32 | 0 | 32 | 0 | 32 |
| EG002 | BMS-986036 Dose Level 3 40 mg | Administered by subcutaneous injection ¹³C-Methacetin Breath Test: 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: Investigational drug for NASH treatment in Main BMS protocol BreathID MCS 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. | 0 | 30 | 0 | 30 | 0 | 30 |
| EG003 | Placebo | Administered by subcutaneous injection ¹³C-Methacetin Breath Test: 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: Investigational drug for NASH treatment in Main BMS protocol BreathID MCS 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. | 0 | 30 | 0 | 30 | 0 | 30 |
Not provided
Not provided