Safety and Effectiveness of BMS-986263 in Adults With Compensated Cirrhosis (Liver Disease) From Nonalcoholic Steatohepatitis (NASH)

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multiple-Dose Phase 2 Study to Evaluate the Efficacy and Safety of BMS-986263 in Adults With Compensated Cirrhosis From Nonalcoholic Steatohepatitis (NASH)

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04267393

Enrollment

124

Registered

2020-02-12

Start date

2021-03-17

Completion date

2024-02-09

Last updated

2024-09-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Nonalcoholic Steatohepatitis (NASH)

Keywords

Nonalcoholic Steatohepatitis, Liver Disease, NASH, Compensated cirrhosis

Brief summary

The purpose of this randomized study is to assess safety and effectiveness of BMS-986263 in adults with compensated cirrhosis (chronic liver disease) from nonalcoholic steatohepatitis (fatty liver disease) (NASH).

Interventions

DRUGBMS-986263

Specified dose on specified days

OTHERPlacebo

Specified dose on specified days

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

21 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Participants with liver biopsy fibrosis score stage 4 (NASH CRN) performed within 12 months * Men and women must agree to follow methods of contraception

Exclusion criteria

* Worsening liver disease or any disease might compromise participant safety in the opinion of the investigator * Known immunocompromised status or any disease or condition which might compromise participant safety * Prior exposure to BMS-986263 * Clinically relevant abnormal physical examination, vital signs, ECG, or clinical laboratory tests * Hepatic decompensation Other protocol-defined inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (NASH CRN Fibrosis Score), as Determined by Liver Biopsy After 12 Weeks of Treatment.	12 Weeks	Percentage of participants who achieve ≥ 1 stage improvement in liver fibrosis (NASH CRN Fibrosis Score), as determined by liver biopsy after 12 weeks of treatment. For the NASH CRN Fibrosis Score, fibrosis is staged on a 0 to 4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis). Responder is defined as achieved \>=1 stage improvement in liver fibrosis (NASH CRN Fibrosis Score) as determined by liver biopsy from baseline to week 12/early treatment termination (ETT).

Secondary

Measure	Time frame	Description
Percentage of Participants Who Achieve ≥ 2 Stage Improvement in Liver Fibrosis (NASH CRN Fibrosis Score) With no Worsening of NASH After 12 Weeks of Treatment.	12 Weeks	Percentage of participants who achieve ≥ 2 stage improvement in liver fibrosis (NASH CRN Fibrosis Score) with no worsening of NASH after 12 weeks of treatment. For the NASH CRN Fibrosis Score, fibrosis is staged on a 0 to 4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
Percentage of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (Modified Ishak Score) After 12 Weeks of Treatment.	12 Weeks	Percentage of participants who achieve ≥ 1 stage improvement in liver fibrosis (modified Ishak score) after 12 weeks of treatment. A modified Ishak scoring system (0 to 6 scale) was originally developed to grade portal-based liver fibrosis associated with viral hepatitis. The modified Ishak system has been adapted to grade central-based liver fibrosis associated with NASH, and it also uses a 0 to 6 scale: 0: No fibrosis 1. perisinusoidal or periportal fibrosis 2. perisinusoidal and portal/periportal fibrosis 3. bridging fibrosis with linkage of \< 50% of vascular structures (portal and centrilobular) 4. bridging fibrosis with linkage of \> 50% of vascular structures (portal and centrilobular) 5. early or incomplete cirrhosis 6. established or advanced cirrhosis
Percentage of Participants Who Achieve ≥ 2 Stage Improvement in Liver Fibrosis (Modified Ishak Score) After 12 Weeks of Treatment.	12 Weeks	Percentage of participants who achieve ≥ 2 stage improvement in liver fibrosis (modified Ishak score) after 12 weeks of treatment. A modified Ishak scoring system (0 to 6 scale) was originally developed to grade portal-based liver fibrosis associated with viral hepatitis. The modified Ishak system has been adapted to grade central-based liver fibrosis associated with NASH, and it also uses a 0 to 6 scale: 0: No fibrosis 1. perisinusoidal or periportal fibrosis 2. perisinusoidal and portal/periportal fibrosis 3. bridging fibrosis with linkage of \< 50% of vascular structures (portal and centrilobular) 4. bridging fibrosis with linkage of \> 50% of vascular structures (portal and centrilobular) 5. early or incomplete cirrhosis 6. established or advanced cirrhosis
Mean Change From Baseline in CPA After 12 Weeks of Treatment	12 Weeks	Change from baseline in CPA after 12 weeks of treatment. Assessment of collagen proportionate area(CPA) is a method by which the amount (percentage) of collagen in stained tissue sections is analyzed using morphometric image analysis. This allows for a quantitative assessment of fibrosis. Percentage of fat in stained tissue sections is also analyzed using morphometric image analysis.
Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Events (TESAE)	From First Treatment to end of Follow up (36 weeks)	An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does have a causal relationship with this treatment.
Percentage of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (NASH CRN Fibrosis Score) With no Worsening of NASH After 12 Weeks of Treatment.	12 Weeks	Percentage of participants who achieve ≥ 1 stage improvement in liver fibrosis (NASH CRN Fibrosis Score) with no worsening of NASH after 12 weeks of treatment. For the NASH CRN Fibrosis Score, fibrosis is staged on a 0 to 4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
Number of Participants With Clinically Significant Changes in Vitals Signs.	From First Treatment to end of Follow up (36 weeks)	Includes body temperature, respiratory rate, blood pressure, and heart rate. Blood pressure and heart rate should be measured after the participant has been resting quietly for at least 5 minutes.
Number of Participants With Clinically Significant Changes in Physical Examination Findings.	From First Treatment to end of Follow up (36 weeks)	Physical examination includes body weight, height, and BMI (height and BMI calculation at screening only).
Number of Participants With Clinically Significant Changes in Electrocardiogram Readings.	From First Treatment to end of Follow up (36 weeks)	Number of Participants with clinically significant changes in electrocardiogram readings.
Number of Participants With Clinically Significant Changes in BMD.	From First Treatment to end of Follow up (36 weeks)	Bone Mineral Density(BMD) will be measured by a dual-energy X-ray absorptiometry (DXA) Scan.
Plasma Concentration of BMS-986263 Components at the End of 12 Weeks or ETT.	12 Weeks	Plasma concentrations of BMS-986263 components: siRNA, DPD, HEDC, and S104.
Number of Participants With Clinically Significant Changes in Clinical Laboratory Values.	From First Treatment to end of Follow up (36 weeks)	Investigators must document their review of each laboratory safety report. A central laboratory will perform the analyses and will provide reference ranges for these tests. clinical laboratory assessments analyzed: Hematology, Blood Chemistry, Urinalysis and a Metabolic Panel.

Countries

Argentina, Belgium, Brazil, Canada, France, Germany, Israel, Italy, Japan, Puerto Rico, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States

Participant flow

Participants by arm

Arm	Count
Placebo Placebo	40
Treatment 1 BMS-986263 45mg QW	42
Treatment 2 BMS-986263 90mg QW	42
Total	124

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Randomization	Administrative Reasons by Sponsor	0	1	0
Randomization	Adverse Event	1	0	0
Treatment Period	Administrative Reasons by Sponsor	3	4	3
Treatment Period	Adverse Event	0	2	3
Treatment Period	Participant Withdrew Consent	0	0	1

Baseline characteristics

Characteristic	Treatment 1	Treatment 2	Total	Placebo
Age, Continuous	58.9 Years STANDARD_DEVIATION 6.76	60.0 Years STANDARD_DEVIATION 8.65	59.3 Years STANDARD_DEVIATION 7.98	58.9 Years STANDARD_DEVIATION 8.56
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants	18 Participants	53 Participants	22 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants	17 Participants	42 Participants	7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants	7 Participants	29 Participants	11 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	11 Participants	9 Participants	26 Participants	6 Participants
Race (NIH/OMB) Black or African American	0 Participants	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	31 Participants	32 Participants	97 Participants	34 Participants
Sex: Female, Male Female	25 Participants	25 Participants	72 Participants	22 Participants
Sex: Female, Male Male	17 Participants	17 Participants	52 Participants	18 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 39	0 / 41	0 / 42
other Total, other adverse events	17 / 39	24 / 41	29 / 42
serious Total, serious adverse events	1 / 39	1 / 41	2 / 42

Outcome results

Primary

Percentage of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (NASH CRN Fibrosis Score), as Determined by Liver Biopsy After 12 Weeks of Treatment.

Percentage of participants who achieve ≥ 1 stage improvement in liver fibrosis (NASH CRN Fibrosis Score), as determined by liver biopsy after 12 weeks of treatment. For the NASH CRN Fibrosis Score, fibrosis is staged on a 0 to 4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis). Responder is defined as achieved \>=1 stage improvement in liver fibrosis (NASH CRN Fibrosis Score) as determined by liver biopsy from baseline to week 12/early treatment termination (ETT).

Time frame: 12 Weeks

Population: Modified Intent to Treat Population (mITT)

Arm	Measure	Value (NUMBER)
Placebo	Percentage of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (NASH CRN Fibrosis Score), as Determined by Liver Biopsy After 12 Weeks of Treatment.	20.5 Percentage
Treatment 1	Percentage of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (NASH CRN Fibrosis Score), as Determined by Liver Biopsy After 12 Weeks of Treatment.	12.2 Percentage
Treatment 2	Percentage of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (NASH CRN Fibrosis Score), as Determined by Liver Biopsy After 12 Weeks of Treatment.	7.1 Percentage

Secondary

Mean Change From Baseline in CPA After 12 Weeks of Treatment

Change from baseline in CPA after 12 weeks of treatment. Assessment of collagen proportionate area(CPA) is a method by which the amount (percentage) of collagen in stained tissue sections is analyzed using morphometric image analysis. This allows for a quantitative assessment of fibrosis. Percentage of fat in stained tissue sections is also analyzed using morphometric image analysis.

Time frame: 12 Weeks

Population: Total number of evaluable participants are those who have both baseline and Week 12/ETT biopsy available

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Mean Change From Baseline in CPA After 12 Weeks of Treatment	-3.67 Percentage	Standard Error 1.861
Treatment 1	Mean Change From Baseline in CPA After 12 Weeks of Treatment	-0.35 Percentage	Standard Error 1.374
Treatment 2	Mean Change From Baseline in CPA After 12 Weeks of Treatment	-3.67 Percentage	Standard Error 1.973

Secondary