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

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03420768
• Collaborator: (none)
• Enrollment: 61
• Location: 1
• Arms: 7
• Actual Duration (Months): 15.4
• Patients Per Site Per Month: 4

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Hepatic Cirrhosis; Liver Fibrosis	Drug: BMS-986263; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Feb 14, 2018
• Actual Primary Completion Date: Dec 10, 2018
• Actual Study Completion Date: May 28, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 BMS-986263 45mg weekly	Drug: BMS-986263; Administered by intravenous (IV) infusion
Experimental: Part 1 BMS-986263 90mg weekly	Drug: BMS-986263; Administered by intravenous (IV) infusion
Placebo Comparator: Part 1 Placebo weekly	Other: Placebo; Administered by intravenous (IV) infusion
Experimental: Part 2 BMS-986263 45mg every 2 weeks	Drug: BMS-986263; Administered by intravenous (IV) infusion
Experimental: Part 2 BMS-986263 90mg every 2 weeks	Drug: BMS-986263; Administered by intravenous (IV) infusion
Experimental: Part 2 BMS-986263 90mg every 4 weeks	Drug: BMS-986263; Administered by intravenous (IV) infusion
Placebo Comparator: Part 2 Placebo every 2 weeks	Other: Placebo; Administered by intravenous (IV) infusion

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. 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 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

3. 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

4. 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 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

5. 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.

6. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Texas Liver Institute	San Antonio	Texas	United States	78215

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

• Study Protocol - Feb 21, 2019
• Statistical Analysis Plan - Feb 19, 2019

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT03420768
• Other Study ID Numbers: IM025-006
• First Posted: Feb 5, 2018
• Last Update Posted: Feb 4, 2022
• Last Verified: Feb 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hepatitis C; Liver Cirrhosis; Fibrosis

Study Results

Participant Flow

Pre-assignment Detail	Per sponsor decision, Part 2 of the study was not initiated. 61 subjects were randomized and treated in Part 1

Arm/Group Title	BMS-986263 45 mg QW (Once Weekly)	BMS-986263 90 mg QW (Once Weekly)	Placebo QW (Once Weekly)
Arm/Group Description	BMS-986263 45 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	BMS-986263 90 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	Placebo will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)
Period Title: Overall Study
STARTED	18	28	15
COMPLETED	18	28	15
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	BMS-986263 45 mg QW (Once Weekly)	BMS-986263 90 mg QW (Once Weekly)	Placebo QW (Once Weekly)	Total
Arm/Group Description	BMS-986263 45 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	BMS-986263 90 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	Placebo will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	Total of all reporting groups
Overall Participants	18	28	15	61
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.2 (7.45)	59.8 (8.24)	61.8 (6.47)	60.4 (7.53)
Sex: Female, Male (Count of Participants)
Female	7 38.9%	12 42.9%	8 53.3%	27 44.3%
Male	11 61.1%	16 57.1%	7 46.7%	34 55.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 72.2%	13 46.4%	6 40%	32 52.5%
Not Hispanic or Latino	5 27.8%	15 53.6%	9 60%	29 47.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 5.6%	0 0%	0 0%	1 1.6%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	2 7.1%	2 13.3%	4 6.6%
White	17 94.4%	26 92.9%	13 86.7%	56 91.8%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat Analysis Set: All participants who are randomized to a treatment and receive at least 1 dose of study medication analyzed as per randomized treatment

Arm/Group Title	BMS-986263 45 mg QW (Once Weekly)	BMS-986263 90 mg QW (Once Weekly)	Placebo QW (Once Weekly)
Arm/Group Description	BMS-986263 45 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	BMS-986263 90 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	Placebo will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)
Measure Participants	18	28	15
Count of Participants [Participants]	3 16.7%	6 21.4%	2 13.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BMS-986263 45 mg QW (Once Weekly)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.30
	Confidence Interval	(2-Sided) 95%; 0.13 to 17.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BMS-986263 90 mg QW (Once Weekly)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.77
	Confidence Interval	(2-Sided) 95%; 0.26 to 20.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat Analysis Set: All participants who are randomized to a treatment and receive at least 1 dose of study medication analyzed as per randomized treatment

Arm/Group Title	BMS-986263 45 mg QW (Once Weekly)	BMS-986263 90 mg QW (Once Weekly)	Placebo QW (Once Weekly)
Arm/Group Description	BMS-986263 45 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	BMS-986263 90 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	Placebo will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)
Measure Participants	18	28	15
Mean (Standard Deviation) [Percent]	-0.68 (2.479)	1.36 (2.946)	-0.21 (1.646)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat Analysis Set: All participants who are randomized to a treatment and receive at least 1 dose of study medication analyzed as per randomized treatment

Arm/Group Title	BMS-986263 45 mg QW (Once Weekly)	BMS-986263 90 mg QW (Once Weekly)	Placebo QW (Once Weekly)
Arm/Group Description	BMS-986263 45 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	BMS-986263 90 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	Placebo will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)
Measure Participants	18	28	15
Count of Participants [Participants]	4 22.2%	7 25%	4 26.7%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat Analysis Set: All participants who are randomized to a treatment and receive at least 1 dose of study medication analyzed as per randomized treatment

Arm/Group Title	BMS-986263 45 mg QW (Once Weekly)	BMS-986263 90 mg QW (Once Weekly)	Placebo QW (Once Weekly)
Arm/Group Description	BMS-986263 45 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	BMS-986263 90 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	Placebo will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)
Measure Participants	18	28	15
Count of Participants [Participants]	0 0%	2 7.1%	0 0%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat Analysis Set: All participants who are randomized to a treatment and receive at least 1 dose of study medication analyzed as per randomized treatment

Arm/Group Title	BMS-986263 45 mg QW (Once Weekly)	BMS-986263 90 mg QW (Once Weekly)	Placebo QW (Once Weekly)
Arm/Group Description	BMS-986263 45 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	BMS-986263 90 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	Placebo will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)
Measure Participants	18	28	15
Count of Participants [Participants]	0 0%	5 17.9%	0 0%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat Analysis Set: All participants who are randomized to a treatment and receive at least 1 dose of study medication analyzed as per randomized treatment

Arm/Group Title	BMS-986263 45 mg QW (Once Weekly)	BMS-986263 90 mg QW (Once Weekly)	Placebo QW (Once Weekly)
Arm/Group Description	BMS-986263 45 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	BMS-986263 90 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	Placebo will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)
Measure Participants	18	28	15
Count of Participants [Participants]	4 22.2%	6 21.4%	3 20%

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat Analysis Set: All participants who are randomized to a treatment and receive at least 1 dose of study medication analyzed as per randomized treatment

Arm/Group Title	BMS-986263 45 mg QW (Once Weekly)	BMS-986263 90 mg QW (Once Weekly)	Placebo QW (Once Weekly)
Arm/Group Description	BMS-986263 45 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	BMS-986263 90 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)	Placebo will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)
Measure Participants	18	28	15
Mean (Standard Deviation) [Change in kPa]	-0.162 (0.5807)	-0.064 (0.7384)	-0.049 (0.5801)

Adverse Events

Time Frame	From first dose of study treatment to 100 days after the last dose of study treatment. (Up to approximately 2 years)
Arm/Group Title	BMS-986263 45 mg QW (Once Weekly)		BMS-986263 90 mg QW (Once Weekly)		Placebo QW (Once Weekly)
Arm/Group Description	BMS-986263 45 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)		BMS-986263 90 mg will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)		Placebo will be administered as an IV infusion QW for a total of 12 weeks in adults with advanced hepatic fibrosis due to Hepatitis C (HCV) who have achieved sustained virologic response (SVR)
All Cause Mortality
	BMS-986263 45 mg QW (Once Weekly)		BMS-986263 90 mg QW (Once Weekly)		Placebo QW (Once Weekly)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/28 (0%)		0/15 (0%)
Serious Adverse Events
	BMS-986263 45 mg QW (Once Weekly)		BMS-986263 90 mg QW (Once Weekly)		Placebo QW (Once Weekly)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		1/28 (3.6%)		0/15 (0%)
Injury, poisoning and procedural complications
Ankle fracture	0/18 (0%)		1/28 (3.6%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	BMS-986263 45 mg QW (Once Weekly)		BMS-986263 90 mg QW (Once Weekly)		Placebo QW (Once Weekly)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/18 (55.6%)		16/28 (57.1%)		8/15 (53.3%)
Blood and lymphatic system disorders
Iron deficiency anaemia	0/18 (0%)		0/28 (0%)		1/15 (6.7%)
Endocrine disorders
Hypothyroidism	1/18 (5.6%)		0/28 (0%)		0/15 (0%)
Gastrointestinal disorders
Constipation	0/18 (0%)		0/28 (0%)		1/15 (6.7%)
Dry mouth	0/18 (0%)		0/28 (0%)		1/15 (6.7%)
General disorders
Fatigue	0/18 (0%)		0/28 (0%)		1/15 (6.7%)
Infections and infestations
Diverticulitis	0/18 (0%)		0/28 (0%)		1/15 (6.7%)
Upper respiratory tract infection	1/18 (5.6%)		1/28 (3.6%)		1/15 (6.7%)
Vulvovaginal candidiasis	1/18 (5.6%)		0/28 (0%)		0/15 (0%)
Injury, poisoning and procedural complications
Infusion related reaction	6/18 (33.3%)		15/28 (53.6%)		0/15 (0%)
Metabolism and nutrition disorders
Gout	0/18 (0%)		0/28 (0%)		1/15 (6.7%)
Musculoskeletal and connective tissue disorders
Back pain	0/18 (0%)		2/28 (7.1%)		2/15 (13.3%)
Muscle spasms	0/18 (0%)		0/28 (0%)		1/15 (6.7%)
Tendonitis	1/18 (5.6%)		0/28 (0%)		0/15 (0%)
Nervous system disorders
Headache	2/18 (11.1%)		1/28 (3.6%)		1/15 (6.7%)
Psychiatric disorders
Abulia	1/18 (5.6%)		0/28 (0%)		0/15 (0%)
Anxiety	0/18 (0%)		1/28 (3.6%)		1/15 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.