Back to resultsA Study of Experimental Medication BMS-986263 in Adults With Advanced Hepatic Fibrosis After Cure of Hepatitis C
Primary Purpose
Hepatic Cirrhosis, Liver Fibrosis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
BMS-986263
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hepatic Cirrhosis
Eligibility Criteria
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
Sites / Locations
- The Texas Liver Institute
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Part 1 BMS-986263 45mg weekly
Part 1 BMS-986263 90mg weekly
Part 1 Placebo weekly
Part 2 BMS-986263 45mg every 2 weeks
Part 2 BMS-986263 90mg every 2 weeks
Part 2 BMS-986263 90mg every 4 weeks
Part 2 Placebo every 2 weeks
Arm Description
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
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
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
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.
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
Full Information
NCT ID
NCT03420768
First Posted
January 29, 2018
Last Updated
February 3, 2022
Sponsor
Bristol-Myers Squibb
1. Study Identification
Unique Protocol Identification Number
NCT03420768
Brief Title
A Study of Experimental Medication BMS-986263 in Adults With Advanced Hepatic Fibrosis After Cure of Hepatitis C
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
February 14, 2018 (Actual)
Primary Completion Date
December 10, 2018 (Actual)
Study Completion Date
May 28, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Cirrhosis, Liver Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
61 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1 BMS-986263 45mg weekly
Arm Type
Experimental
Arm Title
Part 1 BMS-986263 90mg weekly
Arm Type
Experimental
Arm Title
Part 1 Placebo weekly
Arm Type
Placebo Comparator
Arm Title
Part 2 BMS-986263 45mg every 2 weeks
Arm Type
Experimental
Arm Title
Part 2 BMS-986263 90mg every 2 weeks
Arm Type
Experimental
Arm Title
Part 2 BMS-986263 90mg every 4 weeks
Arm Type
Experimental
Arm Title
Part 2 Placebo every 2 weeks
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
BMS-986263
Intervention Description
Administered by intravenous (IV) infusion
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Administered by intravenous (IV) infusion
Primary Outcome Measure Information:
Title
The Number of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (METAVIR Score) as Determined by Liver Biopsy After 12 Weeks of Treatment
Description
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
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Change From Baseline in Collagen Proportionate Area (CPA) After 12 Weeks of Treatment
Description
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
Time Frame
Baseline and Week 12
Title
The Number of Participants With ≥ 1 Stage Improvement in Liver Fibrosis (Ishak Score) After 12 Weeks of Treatment
Description
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
Time Frame
Week 12
Title
The Number of Participants With ≥ 2 Stage Improvement in Liver Fibrosis (METAVIR Score) After 12 Weeks of Treatment
Description
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
Time Frame
Week 12
Title
The Number of Participants With ≥ 2 Stage Improvement in Liver Fibrosis (Ishak Score) After 12 Weeks of Treatment
Description
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
Time Frame
Week 12
Title
The Number of Participants With ≥ 15% Decrease From Baseline in Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE) at Day 85
Description
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.
Time Frame
Baseline and day 85
Title
Change From Baseline in Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE) Day 85
Description
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
Time Frame
Baseline and day 85
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
The Texas Liver Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
34605045
Citation
Lawitz EJ, Shevell DE, Tirucherai GS, Du S, Chen W, Kavita U, Coste A, Poordad F, Karsdal M, Nielsen M, Goodman Z, Charles ED. BMS-986263 in patients with advanced hepatic fibrosis: 36-week results from a randomized, placebo-controlled phase 2 trial. Hepatology. 2022 Apr;75(4):912-923. doi: 10.1002/hep.32181. Epub 2021 Dec 13.
Results Reference
derived
Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting
URL
https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls
Learn more about this trial
A Study of Experimental Medication BMS-986263 in Adults With Advanced Hepatic Fibrosis After Cure of Hepatitis C
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