Trial Outcomes & Findings for A Sub-study of BMS-986036 in Subjects With Non-Alcoholic Steatohepatitis (NASH) (NCT NCT03400163)

Results Overview

The mean change in percent hepatic fat fraction (%) by MRI from baseline to Week 16 was assessed for each arm. A longitudinal repeated measures analysis was used to analyze the change in hepatic fat fraction (%) at Week 16 from baseline in the treated population who have both a baseline and at least one post-baseline measurement.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

From Day 1 to Day 112

Results posted on

2021-02-26

Participant Flow

3 participants were enrolled, randomized and treated within this sub-study (PK cohort). Note: parent study is NCT02413372 (MB130-045).

Participant milestones

Participant milestones
Measure	BMS-986036 20 mg QD Participants self-administered 20 mg subcutaneous (SC) injections of BMS-986036, once daily (QD), for 16 weeks in a double-blind, outpatient setting	Placebo 20 mg QD Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting.
Treatment Period STARTED	1	2
Treatment Period COMPLETED	1	2
Treatment Period NOT COMPLETED	0	0
Follow-up Period STARTED	1	2
Follow-up Period COMPLETED	1	2
Follow-up Period NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Sub-study of BMS-986036 in Subjects With Non-Alcoholic Steatohepatitis (NASH)

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: From Day 1 to Day 112

Population: All treated participants Note: data not reported due to privacy reasons

The mean change in percent hepatic fat fraction (%) by MRI from baseline to Week 16 was assessed for each arm. A longitudinal repeated measures analysis was used to analyze the change in hepatic fat fraction (%) at Week 16 from baseline in the treated population who have both a baseline and at least one post-baseline measurement.

Outcome measures

Outcome measures
Measure	BMS-986036 20 mg QD n=1 Participants Participants self-administered 20 mg subcutaneous (SC) injections of BMS-986036, once daily (QD), for 16 weeks in a double-blind, outpatient setting	Placebo 20 mg QD n=2 Participants Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting.
Mean Change in Percent Hepatic Fat Fraction (%) by Magnetic Resonance Imaging (MRI) From Baseline to Week 16	NA percentage data not reported due to privacy reasons	NA percentage data not reported due to privacy reasons

PRIMARY outcome

Timeframe: From first dose to date of last dose plus 30 days

Population: All treated participants Note: data not reported due to privacy reasons

The number of participants with on-study AEs was reported for each arm.

Outcome measures

Outcome measures
Measure	BMS-986036 20 mg QD n=1 Participants Participants self-administered 20 mg subcutaneous (SC) injections of BMS-986036, once daily (QD), for 16 weeks in a double-blind, outpatient setting	Placebo 20 mg QD n=2 Participants Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting.
Number of Participants With Adverse Events (AEs)	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons

PRIMARY outcome

Timeframe: From first dose to date of last dose plus 30 days

Population: All treated participants Note: data not reported due to privacy reasons

The number of participants with on-study SAEs was reported for each arm.

Outcome measures

Outcome measures
Measure	BMS-986036 20 mg QD n=1 Participants Participants self-administered 20 mg subcutaneous (SC) injections of BMS-986036, once daily (QD), for 16 weeks in a double-blind, outpatient setting	Placebo 20 mg QD n=2 Participants Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting.
Number of Participants With Serious Adverse Events (SAEs)	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons

PRIMARY outcome

Timeframe: From first dose to date of last dose plus 30 days

Population: All treated participants Note: data not reported due to privacy reasons

The number of participants with on-study injection site reactions was reported for each arm.

Outcome measures

Outcome measures
Measure	BMS-986036 20 mg QD n=1 Participants Participants self-administered 20 mg subcutaneous (SC) injections of BMS-986036, once daily (QD), for 16 weeks in a double-blind, outpatient setting	Placebo 20 mg QD n=2 Participants Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting.
Number of Participants With Injection Site Reactions Injection Site Bruising	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons
Number of Participants With Injection Site Reactions Injection Site Erythema	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons
Number of Participants With Injection Site Reactions Injection Site Reaction	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons
Number of Participants With Injection Site Reactions Injection Site Pain	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons
Number of Participants With Injection Site Reactions Injection Site Rash	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons
Number of Participants With Injection Site Reactions Injection Site Swelling	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons

PRIMARY outcome

Timeframe: From first dose to date of last dose plus 30 days

Population: All treated participants Note: data not reported due to privacy reasons

The number of participants with on-study AEs leading to discontinuation was reported for each arm.

Outcome measures

Outcome measures
Measure	BMS-986036 20 mg QD n=1 Participants Participants self-administered 20 mg subcutaneous (SC) injections of BMS-986036, once daily (QD), for 16 weeks in a double-blind, outpatient setting	Placebo 20 mg QD n=2 Participants Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting.
Number of Participants With Adverse Events Leading to Discontinuation	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons

PRIMARY outcome

Timeframe: From first dose to date of last dose plus 30 days

Population: All treated participants Note: data not reported due to privacy reasons

The number of deaths was reported for each arm.

Outcome measures

Outcome measures
Measure	BMS-986036 20 mg QD n=1 Participants Participants self-administered 20 mg subcutaneous (SC) injections of BMS-986036, once daily (QD), for 16 weeks in a double-blind, outpatient setting	Placebo 20 mg QD n=2 Participants Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting.
Number of Deaths	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons

PRIMARY outcome

Timeframe: From first dose to date of last dose plus 30 days

Population: All treated participants Note: data not reported due to privacy reasons

The number of participants whose worst toxicity grade increased from baseline to grade 3 or 4 (Toxicity Scale: DAIDS Version 1.0) is reported for each arm.

Outcome measures

Outcome measures
Measure	BMS-986036 20 mg QD n=1 Participants Participants self-administered 20 mg subcutaneous (SC) injections of BMS-986036, once daily (QD), for 16 weeks in a double-blind, outpatient setting	Placebo 20 mg QD n=2 Participants Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting.
Number of Participants With Marked Laboratory Abnormalities Alanine Aminotransferase (ALT)	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons
Number of Participants With Marked Laboratory Abnormalities Glucose, Fasting - high	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons

PRIMARY outcome

Timeframe: From first dose to date of last dose plus 30 days

Population: All treated participants Note: data not reported due to privacy reasons

The number of participants with out-of-range vital signs noted during interim or final vital sign assessments was reported for each arm.

Outcome measures

Outcome measures
Measure	BMS-986036 20 mg QD n=1 Participants Participants self-administered 20 mg subcutaneous (SC) injections of BMS-986036, once daily (QD), for 16 weeks in a double-blind, outpatient setting	Placebo 20 mg QD n=2 Participants Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting.
Number of Participants With Vital Sign Abnormalities	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons

PRIMARY outcome

Timeframe: From first dose to date of last dose plus 30 days

Population: All treated participants Note: data not reported due to privacy reasons

The number of participants with out-of-range ECG intervals observed during interim or final electrocardiogram assessments was reported for each arm.

Outcome measures

Outcome measures
Measure	BMS-986036 20 mg QD n=1 Participants Participants self-administered 20 mg subcutaneous (SC) injections of BMS-986036, once daily (QD), for 16 weeks in a double-blind, outpatient setting	Placebo 20 mg QD n=2 Participants Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting.
Number of Participants With Electrocardiogram (ECG) Abnormalities PR > 200 msec	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons
Number of Participants With Electrocardiogram (ECG) Abnormalities QRS > 120 msec	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons
Number of Participants With Electrocardiogram (ECG) Abnormalities QT > 500 msec	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcF > 450 msec	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons
Number of Participants With Electrocardiogram (ECG) Abnormalities QT change from baseline > 30 msec	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcF change from baseline > 30 msec	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons

PRIMARY outcome

Timeframe: From first dose to date of last dose plus 30 days

Population: All treated participants Note: data not reported due to privacy reasons

The number of participants with abnormalities observed during interim or final physical examination assessments is reported for each arm.

Outcome measures

Outcome measures
Measure	BMS-986036 20 mg QD n=1 Participants Participants self-administered 20 mg subcutaneous (SC) injections of BMS-986036, once daily (QD), for 16 weeks in a double-blind, outpatient setting	Placebo 20 mg QD n=2 Participants Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting.
Number of Participants With Physical Examination Abnormalities	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons

PRIMARY outcome

Timeframe: From Day 1 to Day 112

Population: All treated participants with DXA data at baseline and 6 months Note: data not reported due to privacy reasons

The mean percent change in bone mineral density from baseline to day 112 reported for each arm.

Outcome measures

Outcome measures
Measure	BMS-986036 20 mg QD n=1 Participants Participants self-administered 20 mg subcutaneous (SC) injections of BMS-986036, once daily (QD), for 16 weeks in a double-blind, outpatient setting	Placebo 20 mg QD n=2 Participants Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting.
Mean Percent Change From Baseline in Bone Mineral Density by Dual Energy X-Ray Absorptiometry (DXA)	NA Percentage Standard Deviation NA data not reported due to privacy reasons	NA Percentage Standard Deviation NA data not reported due to privacy reasons

SECONDARY outcome

Timeframe: From Day 1 to Day 112

Population: All treated participants Note: data not reported due to privacy reasons

The observed serum concentration of BMS-986036 before the next dose is administered (pre-dose concentration) was assessed for both C-terminal intact and total molecule. Geometric means are presented for each arm.

Outcome measures

Outcome measures
Measure	BMS-986036 20 mg QD n=1 Participants Participants self-administered 20 mg subcutaneous (SC) injections of BMS-986036, once daily (QD), for 16 weeks in a double-blind, outpatient setting	Placebo 20 mg QD n=2 Participants Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting.
Geometric Mean of Trough Observed Plasma Concentration (Ctrough) of BMS-986036 at Day 112 C-Terminal Intact	NA ng/mL Geometric Coefficient of Variation NA data not reported due to privacy reasons	NA ng/mL Geometric Coefficient of Variation NA data not reported due to privacy reasons
Geometric Mean of Trough Observed Plasma Concentration (Ctrough) of BMS-986036 at Day 112 Total	NA ng/mL Geometric Coefficient of Variation NA data not reported due to privacy reasons	NA ng/mL Geometric Coefficient of Variation NA data not reported due to privacy reasons

SECONDARY outcome

Timeframe: From Day 1 to Day 142

Population: All treated participants Note: data not reported due to privacy reasons

Participants were monitored for antibodies to study medication using a validated ADA homogenous bridge assay with BMS-986036 and electrochemical luminescence detection. The number of treated participants with positive Anti-BMS-986036 antibody titers up to Day 142 with regards to baseline was reported for each arm.

Outcome measures

Outcome measures
Measure	BMS-986036 20 mg QD n=1 Participants Participants self-administered 20 mg subcutaneous (SC) injections of BMS-986036, once daily (QD), for 16 weeks in a double-blind, outpatient setting	Placebo 20 mg QD n=2 Participants Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting.
Number of Participants With Positive Anti-BMS-986036 Antibody (ADA) Response at Day 142	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons

SECONDARY outcome

Timeframe: From Day 1 to Day 142

Population: All treated participants Note: data not reported due to privacy reasons

Participants were monitored for antibodies to FGF21 using a validated homogenous bridge assay with Met-FGF21 (recombinant produced) and electrochemical luminescence detection. The number of treated participants with positive Anti-FGF21 antibody titers up to Day 142 with regards to baseline was reported for each arm.

Outcome measures

Outcome measures
Measure	BMS-986036 20 mg QD n=1 Participants Participants self-administered 20 mg subcutaneous (SC) injections of BMS-986036, once daily (QD), for 16 weeks in a double-blind, outpatient setting	Placebo 20 mg QD n=2 Participants Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting.
Number of Participants With Positive Anti-FGF21 Antibody Response at Day 142	NA Participants data not reported due to privacy reasons	NA Participants data not reported due to privacy reasons

Adverse Events

BMS-986036 20 mg QD

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo 20 mg QD

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

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	BMS-986036 20 mg QD n=1 Participants Participants self-administered 20 mg subcutaneous (SC) injections of BMS-986036, once daily (QD), for 16 weeks in a double-blind, outpatient setting	Placebo 20 mg QD n=2 Participants Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting.	Total n=3 Participants Total of all reporting groups
Age, Continuous	35 Years STANDARD_DEVIATION NA • n=5 Participants	49.5 Years STANDARD_DEVIATION 2.12 • n=7 Participants	44.67 Years STANDARD_DEVIATION 8.50 • n=5 Participants
Age, Customized < 65 years of age	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Age, Customized >= 65 years of age	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants