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

Phase 2

Completed

• Conditions: Hepatic Cirrhosis; Liver Fibrosis
• Interventions: Other: Placebo; Drug: BMS-986263

• Registration Number: NCT03420768
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

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).

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-01-29
• Study First Submitted QC: 2018-02-01
• Study First Posted: 2018-02-05
• Study Start: 2018-02-14
• Primary Completion: 2018-12-10
• Study Completion: 2019-05-28
• Disposition First Submitted: 2019-12-09
• Results First Submitted: 2021-11-18
• Status Verified: 2022-02
• Results First Submitted QC: 2022-02-03
• Disposition First Submitted QC: 2022-02-03
• Last Update Submitted: 2022-02-03
• Results First Posted: 2022-02-04
• Disposition First Posted: 2022-02-04
• Last Update Posted: 2022-02-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 61

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 1 Placebo weekly	Placebo	-
Part 1 BMS-986263 45mg weekly	BMS-986263	-
Part 1 BMS-986263 90mg weekly	BMS-986263	-
Part 2 BMS-986263 45mg every 2 weeks	BMS-986263	-
Part 2 BMS-986263 90mg every 2 weeks	BMS-986263	-
Part 2 BMS-986263 90mg every 4 weeks	BMS-986263	-
Part 2 Placebo every 2 weeks	Placebo	-

Primary Outcome Measures

Name	Time	Method
The Number of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (METAVIR Score) as Determined by Liver Biopsy After 12 Weeks of Treatment	Week 12	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

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE) Day 85	Baseline and 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
Change From Baseline in Collagen Proportionate Area (CPA) After 12 Weeks of Treatment	Baseline and Week 12	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
The Number of Participants With ≥ 1 Stage Improvement in Liver Fibrosis (Ishak Score) After 12 Weeks of Treatment	Week 12	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; 1. Fibrous expansion of some portal areas, with or without short fibrous septa; 2. Fibrous expansion of most portal areas, with or without short fibrous septa; 3. Fibrous expansion of most portal areas with occasional portal to portal bridging; 4. Fibrous expansion of portal areas with marked bridging (portal to portal as well as portal to central); 5. Marked bridging (portal-portal and/or portal-central) with occasional nodules (incomplete cirrhosis); 6. Cirrhosis, probable or definite
The Number of Participants With ≥ 2 Stage Improvement in Liver Fibrosis (METAVIR Score) After 12 Weeks of Treatment	Week 12	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
The Number of Participants With ≥ 2 Stage Improvement in Liver Fibrosis (Ishak Score) After 12 Weeks of Treatment	Week 12	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; 1. Fibrous expansion of some portal areas, with or without short fibrous septa; 2. Fibrous expansion of most portal areas, with or without short fibrous septa; 3. Fibrous expansion of most portal areas with occasional portal to portal bridging; 4. Fibrous expansion of portal areas with marked bridging (portal to portal as well as portal to central); 5. Marked bridging (portal-portal and/or portal-central) with occasional nodules (incomplete cirrhosis); 6. Cirrhosis, probable or definite
The Number of Participants With ≥ 15% Decrease From Baseline in Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE) at Day 85	Baseline and 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.

Trial Locations

Locations (1)

The Texas Liver Institute; 🇺🇸 San Antonio, Texas, United States