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)
- Conditions
- Nonalcoholic Steatohepatitis10019654
- Registration Number
- NL-OMON53971
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 6
*Male and female participants, ages >= 21 years to <= 75 years of age, inclusive,
at the time of screening;
*Liver biopsy performed within 12 months prior to the screening visit or
performed during the screening period. A liver biopsy performed prior to
informed consent form, if utilized for eligibility, must be available for
central pathology reading prior to Randomization.
i) Liver biopsy consistent with NASH Clinical Research Network (CRN)
Fibrosis
Score Stage 4, as assessed by central pathology reading.
ii) Liver biopsy must either be consistent with steatohepatitis, as
assessed by central
pathology reading, OR, for liver biopsies without definite steatohepatitis,
there should
be some evidence of steatosis and/or ballooning and the following definition of
NASH
cirrhosis must be fulfilled:
(1) Absence of other causes of liver disease AND either of the
following:
(a) At least 2 of the 3 following criteria:
(i) History of body mass index [BMI] >= 30 kg/m2
(ii) History of type 2 diabetes mellitus
(iii) History of hypertension AND/OR history of
dyslipidemia
OR
(b) Previous histologic readings of steatohepatitis (for
biopsies > 12 months prior to screening visit) AND either history of BMI >= 30
kg/m2 OR history
of type 2 diabetes mellitus.
NOTE: At least 80% of participants will be required to have definite
steatohepatitis on
the biopsy used to confirm eligibility.
*Other active causes of liver disease (eg, alcoholic liver disease, hepatitis B
virus infection, chronic hepatitis C virus infection, autoimmune hepatitis,
primary biliary cholangitis, primary sclerosing cholangitis, drug-induced
hepatotoxicity, Wilson disease, homozygous a-1-
antitrypsin deficiency, iron overload [with blood iron saturation > 50%], or
hemochromatosis)
* Past or current evidence of hepatic decompensation (eg, ascites, variceal
bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis)
* Liver transplantation (past or planned)
* Child-Pugh Score > 6 at screening. Participants with a Child-Pugh Score > 6
with elevated total bilirubin and who have Gilbert Syndrome and direct
bilirubin <= the upper limit of normal (ULN) may be included after discussion
with the Medical Monitor
* Model for End-stage Liver Disease (MELD) score > 14 at screening.
Participants with a MELD Score > 14 with elevated total bilirubin and who have
Gilbert Syndrome and direct bilirubin <= the ULN may be included after
discussion with the Medical Monitor
* Evidence of HCC at screening based on (i) serum alpha-fetoprotein (AFP) > 20
ng/mL
(> 16.5 IU/mL) or (ii) Liver Reporting & Data System 3, 4, or 5 as determined
by historical computed tomography (CT)/magnetic resonance imaging (MRI) within
3 months prior to screening or from multiphasic CT/MRI of liver during screening
* The participant*s laboratory test results at screening include any of the
following:
* Albumin < 2.8 g/dL
* INR > 2.2
* Alanine aminotransferase value >= 5× the ULN
* Aspartate aminotransferase value >= 5× the ULN
* Total bilirubin > 3.0 mg/dL, unless participant has a diagnosis of Gilbert
Syndrome and direct bilirubin <= ULN
* Platelet count < 85,000/µL
* Hemoglobin A1c >= 9.0%
* Serum vitamin A (retinol) > ULN
* Inability to safely undergo a liver biopsy in the opinion of the
investigator.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To evaluate the efficacy of BMS-986263 compared with placebo to improve liver<br /><br>fibrosis in participants with compensated cirrhosis due to NASH, by:<br /><br>Proportion of participants who achieve >= 1 stage improvement in liver fibrosis<br /><br>(NASH CRN Fibrosis Score), as determined by liver biopsy after 12 weeks of<br /><br>treatment.</p><br>
- Secondary Outcome Measures
Name Time Method