Trial Outcomes & Findings for Companion Protocol for ¹³C-Methacetin Breath Tests in BMS: NCT03486899, NCT03486912 Referenced Trials (NCT NCT03611101)

NCT ID: NCT03611101

Last Updated: 2022-12-20

Results Overview

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.

• Recruitment status: COMPLETED
• Target enrollment: 124 participants
• Primary outcome timeframe: 48 weeks
• Results posted on: 2022-12-20

Participant Flow

Participant milestones

Measure	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.	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.	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.	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.
Overall Study STARTED	32	32	30	30
Overall Study COMPLETED	25	28	27	23
Overall Study NOT COMPLETED	7	4	3	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	BMS-986036 Dose Level 1 10 mg n=32 Participants 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.	BMS-986036 Dose Level 2 20 mg n=32 Participants 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.	BMS-986036 Dose Level 3 40 mg n=30 Participants 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.	Placebo n=30 Participants 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.	Total n=124 Participants Total of all reporting groups
Age, Continuous	58.906 years STANDARD_DEVIATION 6.981 • n=5 Participants	58.438 years STANDARD_DEVIATION 10.096 • n=7 Participants	59.2 years STANDARD_DEVIATION 9.034 • n=5 Participants	60.433 years STANDARD_DEVIATION 7.338 • n=4 Participants	59.2 years STANDARD_DEVIATION 8.39 • n=21 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	20 Participants n=7 Participants	17 Participants n=5 Participants	17 Participants n=4 Participants	78 Participants n=21 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	12 Participants n=7 Participants	13 Participants n=5 Participants	13 Participants n=4 Participants	46 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants	29 Participants n=7 Participants	29 Participants n=5 Participants	27 Participants n=4 Participants	113 Participants n=21 Participants
Race (NIH/OMB) More than one race	4 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	8 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	32 participants n=5 Participants	32 participants n=7 Participants	30 participants n=5 Participants	30 participants n=4 Participants	124 participants n=21 Participants

PRIMARY outcome

Timeframe: 48 weeks

Population: 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..

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.

Outcome measures

Measure	BMS-986036 Dose Level 1 10 mg n=18 Participants 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.	BMS-986036 Dose Level 2 20 mg n=22 Participants 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.	BMS-986036 Dose Level 3 40 mg n=17 Participants 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.	Placebo n=17 Participants 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.
Percent Change in MBT From Day 1 to Week 48	8.8 percentage of change in MBT Standard Deviation 32.51	12.3 percentage of change in MBT Standard Deviation 33.36	-4.7 percentage of change in MBT Standard Deviation 27.64	15.3 percentage of change in MBT Standard Deviation 31.58

SECONDARY outcome

Timeframe: 48 weeks

Binary diagnosis of subjects that experience deterioration event as determined by the MBT compared to the placebo treatment arm

Outcome measures

Measure	BMS-986036 Dose Level 1 10 mg n=32 Participants 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.	BMS-986036 Dose Level 2 20 mg n=32 Participants 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.	BMS-986036 Dose Level 3 40 mg n=30 Participants 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.	Placebo n=30 Participants 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.
Number of Subjects That Experience Deterioration Events	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 48 weeks

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.

Outcome measures

Measure	BMS-986036 Dose Level 1 10 mg n=9 Participants 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.	BMS-986036 Dose Level 2 20 mg n=12 Participants 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.	BMS-986036 Dose Level 3 40 mg n=8 Participants 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.	Placebo n=10 Participants 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.
Correlation	-0.324 r-correlation	-0.501 r-correlation	0.275 r-correlation	-0.313 r-correlation

SECONDARY outcome

Timeframe: 48 weeks

Correlation of MBT changes to changes in liver stiffness as measured by Magnetic Resonance Elastography (MRE) from Day 1 to Week 48

Outcome measures

Measure	BMS-986036 Dose Level 1 10 mg n=13 Participants 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.	BMS-986036 Dose Level 2 20 mg n=15 Participants 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.	BMS-986036 Dose Level 3 40 mg n=13 Participants 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.	Placebo n=16 Participants 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.
Correlation	0.279 r-correlation	-0.115 r-correlation	-0.428 r-correlation	0.242 r-correlation

SECONDARY outcome

Timeframe: 48 weeks

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

Outcome measures

Measure	BMS-986036 Dose Level 1 10 mg n=16 Participants 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.	BMS-986036 Dose Level 2 20 mg n=21 Participants 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.	BMS-986036 Dose Level 3 40 mg n=14 Participants 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.	Placebo n=17 Participants 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.
Correlation	-0.202 r-correlation	-0.047 r-correlation	0.248 r-correlation	-0.044 r-correlation

SECONDARY outcome

Timeframe: 48 weeks

Correlation of MBT changes to changes in Serum Pro-C3 results from Day 1 to Week 48

Outcome measures

Measure	BMS-986036 Dose Level 1 10 mg n=17 Participants 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.	BMS-986036 Dose Level 2 20 mg n=22 Participants 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.	BMS-986036 Dose Level 3 40 mg n=16 Participants 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.	Placebo n=16 Participants 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.
Correlation	-0.001 r-correlation	0.242 r-correlation	-0.263 r-correlation	-0.072 r-correlation

SECONDARY outcome

Timeframe: 48 weeks

Correlation of MBT changes to changes in liver elastography by Fibroscan (in cohort 2 only) from Day 1 to Week 48

Outcome measures

Measure	BMS-986036 Dose Level 1 10 mg n=9 Participants 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.	BMS-986036 Dose Level 2 20 mg n=11 Participants 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.	BMS-986036 Dose Level 3 40 mg n=8 Participants 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.	Placebo n=11 Participants 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.
Correlation	0.491 r-correlation	-0.351 r-correlation	-0.121 r-correlation	-0.43 r-correlation

SECONDARY outcome

Timeframe: 48 weeks

Population: 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.

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.

Outcome measures

Measure	BMS-986036 Dose Level 1 10 mg n=17 Participants 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.	BMS-986036 Dose Level 2 20 mg n=22 Participants 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.	BMS-986036 Dose Level 3 40 mg n=16 Participants 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.	Placebo n=17 Participants 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.
Correlation	NA r-correlation 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.	NA r-correlation 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.	NA r-correlation 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.	NA r-correlation 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.

SECONDARY outcome

Timeframe: 48 weeks

Population: 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.

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

Outcome measures

Measure	BMS-986036 Dose Level 1 10 mg n=32 Participants 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.	BMS-986036 Dose Level 2 20 mg n=30 Participants 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.	BMS-986036 Dose Level 3 40 mg n=30 Participants 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.	Placebo n=30 Participants 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.
Correlation	NA r-correlation 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.	NA r-correlation 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.	NA r-correlation 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.	NA r-correlation 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.

Adverse Events

BMS-986036 Dose Level 1 10 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

BMS-986036 Dose Level 2 20 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

BMS-986036 Dose Level 3 40 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Clinical Trial Manager

Exalenz Bioscience

Phone: +972-8-9737513

Email: avrahamh@exalenz.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place