A Study of Experimental Medication BMS-986263 in Adults With Advanced Hepatic Fibrosis After Cure of Hepatitis C

Study Overview
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Brief Summary
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This is a study of experimental medication BMS-986263 in adult patients with advanced hepatic fibrosis (scar tissue in the liver caused by inflammation that is far on in progress) after the patient is cured of hepatitis C (an infection caused by a virus that attacks the liver and leads to inflammation).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multiple Dose Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BMS-986263 in Adults With Advanced Hepatic Fibrosis After Virologic Cure of Hepatitis C

Conditions
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Hepatic Cirrhosis, Liver Fibrosis

Intervention / Treatment
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* Drug: BMS-986263
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Participants must provide documentation showing a sustained virologic response (SVR) for at least 1 year (52 weeks) prior to the date of screening (SVR is defined as a negative hepatitis C RNA greater than or equal to 12 weeks from the end of therapy) Participants must have METAVIR Stage 3 or 4 (or equivalent if using other classification; eg, Ishak) Exclusion Criteria: Other causes of liver disease (eg, alcoholic liver disease, HBV [serologically positive as determined using United States Centers for Disease Control and Prevention guidance for interpretation of hepatitis B serologic test results], autoimmune hepatitis, drug-induced hepatotoxicity, Wilson disease, iron overload, alpha-1-antitrypsin deficiency, NASH, hemochromatosis) Participants having liver diseases associated with infection with any other hepatitis virus Detectable HCV RNA at screening Child-Pugh score > 6 Model for End-Stage Liver Disease score >12 Evidence of HCC at screening based on alpha-fetoprotein (AFP) levels: AFP > 100 ng/mL (> 82.6 IU/mL) OR AFP ≥ 50 and ≤ 100 ng/mL (≥ 41.3 IU/mL and ≤ 82.6 IU/ mL) with liver ultrasound showing findings suspicious for HCC, or any imaging technique (eg, magnetic resonance imaging [MRI] or computed tomography; based on local assessment), or ultrasound Blood transfusion in the last 6 months prior to screening due to the risk of re-infection with HCV, HBV, HIV, etc Participant has any disease or condition which, in the opinion of the investigator, might compromise patient safety (eg, hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, skeletal, central nervous system, or compliment-mediated disease); or other conditions that may interfere with the absorption, distribution, metabolism, or excretion of BMS 986263, or would place the participant at increased risk Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 BMS-986263 45mg weekly<br> | Drug: BMS-986263<br>* Administered by intravenous (IV) infusion<br>|
| Experimental: Part 1 BMS-986263 90mg weekly<br> | Drug: BMS-986263<br>* Administered by intravenous (IV) infusion<br>|
| Placebo Comparator: Part 1 Placebo weekly<br> | Other: Placebo<br>* Administered by intravenous (IV) infusion<br>|
| Experimental: Part 2 BMS-986263 45mg every 2 weeks<br> | Drug: BMS-986263<br>* Administered by intravenous (IV) infusion<br>|
| Experimental: Part 2 BMS-986263 90mg every 2 weeks<br> | Drug: BMS-986263<br>* Administered by intravenous (IV) infusion<br>|
| Experimental: Part 2 BMS-986263 90mg every 4 weeks<br> | Drug: BMS-986263<br>* Administered by intravenous (IV) infusion<br>|
| Placebo Comparator: Part 2 Placebo every 2 weeks<br> | Other: Placebo<br>* Administered by intravenous (IV) infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (METAVIR Score) as Determined by Liver Biopsy After 12 Weeks of Treatment | The number of participants who achieve ≥ 1 stage improvement in liver fibrosis is used to asses the effects of treatment compared to placebo. The METAVIR system is used to assess the extent of inflammation and fibrosis by histopathological evaluation in a liver biopsy of patients with hepatitis C virus (HCV). It assesses liver biopsies for activity grade (A0-A3) and fibrosis stage (Stage 1 - 4). Participants without a measurement at Week 12 are considered non-responders. Activity Grade: A0 = no activity; A1 = mild activity; A2 = moderate activity; A3 = severe activity Fibrosis stage: 1 = portal fibrosis without septa ; 2 = portal fibrosis with few septa; 3 = numerous septa without cirrhosis; 4 = cirrhosis | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Collagen Proportionate Area (CPA) After 12 Weeks of Treatment | The change from baseline measurement in Collagen Proportionate Area (CPA) is used to asses the effects of treatment compared to placebo. Assessment of CPA is a method by which the amount (percentage) of collagen in stained tissue sections is analyzed using morphometric image analysis | Baseline and Week 12 | 
| The Number of Participants With ≥ 1 Stage Improvement in Liver Fibrosis (Ishak Score) After 12 Weeks of Treatment | The number of participants with ≥ 1 stage improvement in liver fibrosis is used to asses the effects of treatment compared to placebo. The Ishak scoring system is used to grade fibrosis in the histology samples. The Ishak system (0 through 6 scale) was developed to grade portal-based liver fibrosis associated with viral hepatitis: 0: No fibrosis Fibrous expansion of some portal areas, with or without short fibrous septa Fibrous expansion of most portal areas, with or without short fibrous septa Fibrous expansion of most portal areas with occasional portal to portal bridging Fibrous expansion of portal areas with marked bridging (portal to portal as well as portal to central) Marked bridging (portal-portal and/or portal-central) with occasional nodules (incomplete cirrhosis) Cirrhosis, probable or definite | Week 12 | 
| The Number of Participants With ≥ 2 Stage Improvement in Liver Fibrosis (METAVIR Score) After 12 Weeks of Treatment | The number of participants with ≥ 2 stage improvement in liver fibrosis is used to asses the effects of treatment compared to placebo. The METAVIR system is used to assess the extent of inflammation and fibrosis by histopathological evaluation in a liver biopsy of patients with hepatitis C virus (HCV). It assesses liver biopsies for activity grade (A0-A3) and fibrosis stage (Stage 1 - 4). Participants without a measurement at Week 12 are considered non-responders. Activity Grade: A0 = no activity; A1 = mild activity; A2 = moderate activity; A3 = severe activity Fibrosis stage: 1 = portal fibrosis without septa ; 2 = portal fibrosis with few septa; 3 = numerous septa without cirrhosis; 4 = cirrhosis | Week 12 | 
| The Number of Participants With ≥ 2 Stage Improvement in Liver Fibrosis (Ishak Score) After 12 Weeks of Treatment | The number of participants with ≥ 2 stage improvement in liver fibrosis is used to asses the effects of treatment compared to placebo. The Ishak scoring system is used to grade fibrosis in the histology samples. The Ishak system (0 through 6 scale) was developed to grade portal-based liver fibrosis associated with viral hepatitis: 0: No fibrosis Fibrous expansion of some portal areas, with or without short fibrous septa Fibrous expansion of most portal areas, with or without short fibrous septa Fibrous expansion of most portal areas with occasional portal to portal bridging Fibrous expansion of portal areas with marked bridging (portal to portal as well as portal to central) Marked bridging (portal-portal and/or portal-central) with occasional nodules (incomplete cirrhosis) Cirrhosis, probable or definite | Week 12 | 
| The Number of Participants With ≥ 15% Decrease From Baseline in Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE) at Day 85 | The number of participants with ≥ 15% decrease from baseline in liver stiffness is used to asses the effects of treatment compared to placebo Magnetic resonance elastography (MRE) is a noninvasive medical imaging technique that quantitatively measures the stiffness of soft tissues by introducing shear waves and imaging their propagation using magnetic resonance imaging (MRI). MRE will be used to quantitate liver stiffness as a surrogate biomarker of liver fibrosis. | Baseline and day 85 | 
| Change From Baseline in Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE) Day 85 | Change from baseline in liver stiffness is used to asses the effects of treatment compared to placebo. Magnetic resonance elastography (MRE) is a noninvasive medical imaging technique that quantitatively measures the stiffness of soft tissues by introducing shear waves and imaging their propagation using magnetic resonance imaging (MRI). MRE will be used to quantitate liver stiffness as a surrogate biomarker of liver fibrosis | Baseline and day 85 |