Non-Alcoholic Steatohepatitis
Conditions
Keywords
First Line Therapy, NASH
Brief summary
The purpose of this sub-study of MB130-045 is to determine the pharmacokinetic effects, pharmacodynamic effects, efficacy and safety of BMS-986036 20 mg QD in subjects with Non-alcoholic Steatohepatitis (NASH)
Interventions
DRUGBMS-986036
BMS-986036 20 mg QD
DRUGPlacebo
Placebo QD
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Male or female between 21 and 75 years old * Body Mass Index (BMI) of 25 or more
Exclusion criteria
* Chronic Liver disease other than NASH * Uncontrolled diabetes * Any major surgery within 6 weeks of screening * Unable to self-administer under the skin injections * Any bone trauma, fracture or bone surgery within 8 weeks of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline in Bone Mineral Density by Dual Energy X-Ray Absorptiometry (DXA) | From Day 1 to Day 112 | The mean percent change in bone mineral density from baseline to day 112 reported for each arm. |
| Number of Participants With Vital Sign Abnormalities | From first dose to date of last dose plus 30 days | The number of participants with out-of-range vital signs noted during interim or final vital sign assessments was reported for each arm. |
| Number of Participants With Electrocardiogram (ECG) Abnormalities | From first dose to date of last dose plus 30 days | The number of participants with out-of-range ECG intervals observed during interim or final electrocardiogram assessments was reported for each arm. |
| Number of Participants With Physical Examination Abnormalities | From first dose to date of last dose plus 30 days | The number of participants with abnormalities observed during interim or final physical examination assessments is reported for each arm. |
| Mean Change in Percent Hepatic Fat Fraction (%) by Magnetic Resonance Imaging (MRI) From Baseline to Week 16 | From Day 1 to Day 112 | 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. |
| Number of Participants With Adverse Events (AEs) | From first dose to date of last dose plus 30 days | The number of participants with on-study AEs was reported for each arm. |
| Number of Participants With Serious Adverse Events (SAEs) | From first dose to date of last dose plus 30 days | The number of participants with on-study SAEs was reported for each arm. |
| Number of Participants With Injection Site Reactions | From first dose to date of last dose plus 30 days | The number of participants with on-study injection site reactions was reported for each arm. |
| Number of Participants With Adverse Events Leading to Discontinuation | From first dose to date of last dose plus 30 days | The number of participants with on-study AEs leading to discontinuation was reported for each arm. |
| Number of Deaths | From first dose to date of last dose plus 30 days | The number of deaths was reported for each arm. |
| Number of Participants With Marked Laboratory Abnormalities | From first dose to date of last dose plus 30 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Positive Anti-BMS-986036 Antibody (ADA) Response at Day 142 | From Day 1 to Day 142 | 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. |
| Number of Participants With Positive Anti-FGF21 Antibody Response at Day 142 | From Day 1 to Day 142 | 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. |
| Geometric Mean of Trough Observed Plasma Concentration (Ctrough) of BMS-986036 at Day 112 | From Day 1 to Day 112 | 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. |
Countries
United States
Participant flow
Pre-assignment details
3 participants were enrolled, randomized and treated within this sub-study (PK cohort). Note: parent study is NCT02413372 (MB130-045).
Participants by arm
| Arm | Count |
|---|---|
| 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 | 1 |
| Placebo 20 mg QD Participants self-administered SC injections of placebo, once daily, for 16 weeks in a double-blind, outpatient setting. | 2 |
| Total | 3 |
Baseline characteristics
| Characteristic | BMS-986036 20 mg QD | Placebo 20 mg QD | Total |
|---|---|---|---|
| Age, Continuous | 35 Years | 49.5 Years STANDARD_DEVIATION 2.12 | 44.67 Years STANDARD_DEVIATION 8.5 |
| Age, Customized < 65 years of age | 1 Participants | 2 Participants | 3 Participants |
| Age, Customized >= 65 years of age | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Mean Change in Percent Hepatic Fat Fraction (%) by Magnetic Resonance Imaging (MRI) From Baseline to Week 16
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.
Time frame: From Day 1 to Day 112
Population: All treated participants~Note: data not reported due to privacy reasons
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BMS-986036 20 mg QD | Mean Change in Percent Hepatic Fat Fraction (%) by Magnetic Resonance Imaging (MRI) From Baseline to Week 16 | NA percentage |
| Placebo 20 mg QD | Mean Change in Percent Hepatic Fat Fraction (%) by Magnetic Resonance Imaging (MRI) From Baseline to Week 16 | NA percentage |
Primary
Mean Percent Change From Baseline in Bone Mineral Density by Dual Energy X-Ray Absorptiometry (DXA)
The mean percent change in bone mineral density from baseline to day 112 reported for each arm.
Time frame: 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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BMS-986036 20 mg QD | Mean Percent Change From Baseline in Bone Mineral Density by Dual Energy X-Ray Absorptiometry (DXA) | NA Percentage |
| Placebo 20 mg QD | Mean Percent Change From Baseline in Bone Mineral Density by Dual Energy X-Ray Absorptiometry (DXA) | NA Percentage |
Primary
Number of Deaths
The number of deaths was reported for each arm.
Time frame: From first dose to date of last dose plus 30 days
Population: All treated participants~Note: data not reported due to privacy reasons
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986036 20 mg QD | Number of Deaths | NA Participants |
| Placebo 20 mg QD | Number of Deaths | NA Participants |
Primary
Number of Participants With Adverse Events (AEs)
The number of participants with on-study AEs was reported for each arm.
Time frame: From first dose to date of last dose plus 30 days
Population: All treated participants~Note: data not reported due to privacy reasons
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986036 20 mg QD | Number of Participants With Adverse Events (AEs) | NA Participants |
| Placebo 20 mg QD | Number of Participants With Adverse Events (AEs) | NA Participants |
Primary
Number of Participants With Adverse Events Leading to Discontinuation
The number of participants with on-study AEs leading to discontinuation was reported for each arm.
Time frame: From first dose to date of last dose plus 30 days
Population: All treated participants~Note: data not reported due to privacy reasons
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986036 20 mg QD | Number of Participants With Adverse Events Leading to Discontinuation | NA Participants |
| Placebo 20 mg QD | Number of Participants With Adverse Events Leading to Discontinuation | NA Participants |
Primary
Number of Participants With Electrocardiogram (ECG) Abnormalities
The number of participants with out-of-range ECG intervals observed during interim or final electrocardiogram assessments was reported for each arm.
Time frame: From first dose to date of last dose plus 30 days
Population: All treated participants~Note: data not reported due to privacy reasons
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BMS-986036 20 mg QD | Number of Participants With Electrocardiogram (ECG) Abnormalities | PR > 200 msec | NA Participants |
| BMS-986036 20 mg QD | Number of Participants With Electrocardiogram (ECG) Abnormalities | QRS > 120 msec | NA Participants |
| BMS-986036 20 mg QD | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT > 500 msec | NA Participants |
| BMS-986036 20 mg QD | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF > 450 msec | NA Participants |
| BMS-986036 20 mg QD | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT change from baseline > 30 msec | NA Participants |
| BMS-986036 20 mg QD | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF change from baseline > 30 msec | NA Participants |
| Placebo 20 mg QD | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT change from baseline > 30 msec | NA Participants |
| Placebo 20 mg QD | Number of Participants With Electrocardiogram (ECG) Abnormalities | PR > 200 msec | NA Participants |
| Placebo 20 mg QD | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF > 450 msec | NA Participants |
| Placebo 20 mg QD | Number of Participants With Electrocardiogram (ECG) Abnormalities | QRS > 120 msec | NA Participants |
| Placebo 20 mg QD | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF change from baseline > 30 msec | NA Participants |
| Placebo 20 mg QD | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT > 500 msec | NA Participants |
Primary
Number of Participants With Injection Site Reactions
The number of participants with on-study injection site reactions was reported for each arm.
Time frame: From first dose to date of last dose plus 30 days
Population: All treated participants~Note: data not reported due to privacy reasons
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BMS-986036 20 mg QD | Number of Participants With Injection Site Reactions | Injection Site Reaction | NA Participants |
| BMS-986036 20 mg QD | Number of Participants With Injection Site Reactions | Injection Site Bruising | NA Participants |
| BMS-986036 20 mg QD | Number of Participants With Injection Site Reactions | Injection Site Erythema | NA Participants |
| BMS-986036 20 mg QD | Number of Participants With Injection Site Reactions | Injection Site Pain | NA Participants |
| BMS-986036 20 mg QD | Number of Participants With Injection Site Reactions | Injection Site Rash | NA Participants |
| BMS-986036 20 mg QD | Number of Participants With Injection Site Reactions | Injection Site Swelling | NA Participants |
| Placebo 20 mg QD | Number of Participants With Injection Site Reactions | Injection Site Rash | NA Participants |
| Placebo 20 mg QD | Number of Participants With Injection Site Reactions | Injection Site Pain | NA Participants |
| Placebo 20 mg QD | Number of Participants With Injection Site Reactions | Injection Site Bruising | NA Participants |
| Placebo 20 mg QD | Number of Participants With Injection Site Reactions | Injection Site Swelling | NA Participants |
| Placebo 20 mg QD | Number of Participants With Injection Site Reactions | Injection Site Erythema | NA Participants |
| Placebo 20 mg QD | Number of Participants With Injection Site Reactions | Injection Site Reaction | NA Participants |
Primary
Number of Participants With Marked Laboratory Abnormalities
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.
Time frame: From first dose to date of last dose plus 30 days
Population: All treated participants~Note: data not reported due to privacy reasons
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BMS-986036 20 mg QD | Number of Participants With Marked Laboratory Abnormalities | Alanine Aminotransferase (ALT) | NA Participants |
| BMS-986036 20 mg QD | Number of Participants With Marked Laboratory Abnormalities | Glucose, Fasting - high | NA Participants |
| Placebo 20 mg QD | Number of Participants With Marked Laboratory Abnormalities | Alanine Aminotransferase (ALT) | NA Participants |
| Placebo 20 mg QD | Number of Participants With Marked Laboratory Abnormalities | Glucose, Fasting - high | NA Participants |
Primary
Number of Participants With Physical Examination Abnormalities
The number of participants with abnormalities observed during interim or final physical examination assessments is reported for each arm.
Time frame: From first dose to date of last dose plus 30 days
Population: All treated participants~Note: data not reported due to privacy reasons
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986036 20 mg QD | Number of Participants With Physical Examination Abnormalities | NA Participants |
| Placebo 20 mg QD | Number of Participants With Physical Examination Abnormalities | NA Participants |
Primary
Number of Participants With Serious Adverse Events (SAEs)
The number of participants with on-study SAEs was reported for each arm.
Time frame: From first dose to date of last dose plus 30 days
Population: All treated participants~Note: data not reported due to privacy reasons
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986036 20 mg QD | Number of Participants With Serious Adverse Events (SAEs) | NA Participants |
| Placebo 20 mg QD | Number of Participants With Serious Adverse Events (SAEs) | NA Participants |
Primary
Number of Participants With Vital Sign Abnormalities
The number of participants with out-of-range vital signs noted during interim or final vital sign assessments was reported for each arm.
Time frame: From first dose to date of last dose plus 30 days
Population: All treated participants~Note: data not reported due to privacy reasons
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986036 20 mg QD | Number of Participants With Vital Sign Abnormalities | NA Participants |
| Placebo 20 mg QD | Number of Participants With Vital Sign Abnormalities | NA Participants |
Secondary
Geometric Mean of Trough Observed Plasma Concentration (Ctrough) of BMS-986036 at Day 112
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.
Time frame: From Day 1 to Day 112
Population: All treated participants~Note: data not reported due to privacy reasons
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BMS-986036 20 mg QD | Geometric Mean of Trough Observed Plasma Concentration (Ctrough) of BMS-986036 at Day 112 | C-Terminal Intact | NA ng/mL |
| BMS-986036 20 mg QD | Geometric Mean of Trough Observed Plasma Concentration (Ctrough) of BMS-986036 at Day 112 | Total | NA ng/mL |
| Placebo 20 mg QD | Geometric Mean of Trough Observed Plasma Concentration (Ctrough) of BMS-986036 at Day 112 | C-Terminal Intact | NA ng/mL |
| Placebo 20 mg QD | Geometric Mean of Trough Observed Plasma Concentration (Ctrough) of BMS-986036 at Day 112 | Total | NA ng/mL |
Secondary
Number of Participants With Positive Anti-BMS-986036 Antibody (ADA) Response at Day 142
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.
Time frame: From Day 1 to Day 142
Population: All treated participants~Note: data not reported due to privacy reasons
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986036 20 mg QD | Number of Participants With Positive Anti-BMS-986036 Antibody (ADA) Response at Day 142 | NA Participants |
| Placebo 20 mg QD | Number of Participants With Positive Anti-BMS-986036 Antibody (ADA) Response at Day 142 | NA Participants |
Secondary
Number of Participants With Positive Anti-FGF21 Antibody Response at Day 142
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.
Time frame: From Day 1 to Day 142
Population: All treated participants~Note: data not reported due to privacy reasons
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986036 20 mg QD | Number of Participants With Positive Anti-FGF21 Antibody Response at Day 142 | NA Participants |
| Placebo 20 mg QD | Number of Participants With Positive Anti-FGF21 Antibody Response at Day 142 | NA Participants |