Safety and Efficacy Study in Subjects With Chronic HCV and Underlying Hemophilia (MAGNITUDE)

A Phase 3 Study Evaluating the Safety and Efficacy of Lambda/Ribavirin/Daclatasvir in Subjects With Chronic HCV Infection and Underlying Hemophilia Who Are Treatment Naïve or Are Prior Relapsers to Peginterferon Alfa-2a/Ribavirin

The primary objective for this study is to evaluate the proportion of subjects who achieve SVR12 (HCV RNA < LLOQ (target not detected) at post-treatment follow-up Week 12 in subjects with Genotype(GT)-1b, -4 and GT-2, -3

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus
• Intervention / Treatment: Drug: Ribavirin; Drug: Daclatasvir; Biological: Pegylated-Interferon-lambda

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Herston, Australia, 4029
    • Local Institution
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Local Institution
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Local Institution
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Local Institution
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Local Institution
• France
  • Grenoble, France, 38043
    • Local Institution
  • Lyon Cedex 04, France, 69317
    • Local Institution
  • Montpellier Cedex 5, France, 34295
    • Local Institution
  • Paris Cedex 13, France, 75651
    • Local Institution
  • Paris Cedex 14, France, 75679
    • Local Institution
  • Vandoeuvre Les Nancy, France, 54511
    • Local Institution
• Italy
  • Firenze, Italy, 50134
    • Local Institution
  • Milan, Italy, 20122
    • Local Institution
  • Roma, Italy, 00185
    • Local Institution
  • Torino, Italy, 10126
    • Local Institution
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Local Institution
  • Nijmegen, Netherlands, 6525 GA
    • Local Institution
  • Rotterdam, Netherlands, 3015 CE
    • Local Institution
  • Utrecht, Netherlands, 3508 GA
    • Local Institution
• Romania
  • Bucuresti, Romania, 50524
    • Local Institution
  • Constanta, Romania, 900635
    • Local Institution
  • Iasi, Romania, 700506
    • Local Institution
  • Iasi, Romania, 700116
    • Local Institution
• Russian Federation
  • Moscow, Russian Federation, 107996
    • Local Institution
  • Saint Petersburg, Russian Federation, 191186
    • Local Institution
• Spain
  • Barcelona, Spain, 08035
    • Local Institution
  • Madrid, Spain, 28046
    • Local Institution
  • Sevilla, Spain, 41013
    • Local Institution
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford Boswell Clinic
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • Utah
    • Murray, Utah, United States, 84123
      • Clinical Research Centers Of America

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

• Severe hemophilia (defined as < 1% factor activity level)
• Infection with the hepatitis C virus (HCV) with underlying hemophilia
• Males 18 years of age and above
• Have not been previously treated with an interferon

Exclusion Criteria:

• Not infected with the hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
• Chronic liver disease caused by any disease other than chronic HCV infection
• Presence of Bethesda inhibitor
• Current evidence of or history of portal hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Genotype-2,-3 (Lambda/RBV/DCV); Lambda 180 μg solution for subcutaneous (SC) injection, once weekly for 12 weeks Ribavirin (RBV) 200 mg tablet by mouth (oral), twice daily for 12 weeks Daclatasvir (DCV) 60mg tablet by mouth (oral), once daily for 12 weeks	Drug: Ribavirin; Drug: Daclatasvir; Other Names: BMS-790052; Biological: Pegylated-Interferon-lambda; Other Names: BMS-914143; pegIFNλ
Experimental: Cohort B: Genotype-1b,-4 (Lambda/RBV/DCV); Lambda 180 μg solution for subcutaneous (SC) injection, once weekly for 24 weeks Ribavirin (RBV) 200 mg tablet by mouth (oral), twice daily for 24 weeks Daclatasvir (DCV) 60mg tablet by mouth (oral), once daily for 12 weeks	Drug: Ribavirin; Drug: Daclatasvir; Other Names: BMS-790052; Biological: Pegylated-Interferon-lambda; Other Names: BMS-914143; pegIFNλ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Sustained Virologic Response (SVR12) at Follow-Up Week 12	SVR12 was defined as HCV ribonucleic acid (RNA) less than the lower limit of quantitation, target detected or target not detected at follow-up Week 12.	Follow-up Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Rapid Virologic Response (RVR)	RVR was defined as HCV RNA less than the lower limit of quantitation, target not detected at Week 4.	Treatment Week 4
Percentage of Participants With Complete Early Virologic Response (cEVR)	cEVR was defined as HCV RNA less than the lower limit of quantitation, target not detected at Week 12.	Treatment Week 12
Percentage of Participants With End of the Treatment Response (EOTR)	EOTR was defined as HCV RNA less than the lower limit of quantitation, target not detected at end of treatment.	End of the treatment (Week 12 for Cohort A, Week 24 for Cohort B)
Percentage of Participants With Sustained Virologic Response at Follow-Up Week 24 (SVR24)	SVR24 was defined as HCV RNA less than the lower limit of quantitation, target detected or target not detected at follow-up week 24.	Follow-up Week 24
Percentage of Participants With Treatment-Emergent Cytopenic Abnormalities On-Treatment	Cytopenic abnormalities were defined as anemia: Hemoglobin (Hb) <10 g/dL, and/or neutropenia: absolute neutrophils and bands (ANC) <750 mm^3, and/or thrombocytopenia: platelets <50,000 mm^3.	After day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)
Percentage of Participants With Flu-Like Symptoms and Musculoskeletal Symptoms On-Treatment	Flu-like symptoms were defined as pyrexia or chills or pain. Musculoskeletal symptoms were defined as arthralgia or myalgia or back pain.	After day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death	AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Treatment-related SAE=possibly, probably, or certainly related to study drug.	From Day 1 to end of follow-up (maximum of 60 weeks for Cohort A and 72 weeks for Cohort B)
Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities	Laboratory abnormalities were determined and graded using the Division of acquired immunodeficiency syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, version 1.0. International Normalized Ratio (INR): >2.0*Upper limit of normal (ULN); Alanine aminotransferase (ALT) : >5*ULN; Aspartate aminotransferase (AST): >5*ULN; Prothrombin Time (PT): >1.50*ULN; Bilirubin (Total): >2.5*ULN; Triglycerides (fasting): >750 mg/dL.	After day 1 to to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2013
• Primary Completion (Actual): January 31, 2015
• Study Completion (Actual): January 31, 2015

Study Registration Dates

• First Submitted: December 3, 2012
• First Submitted That Met QC Criteria: December 3, 2012
• First Posted (Estimate): December 5, 2012

Study Record Updates

• Last Update Posted (Actual): August 11, 2020
• Last Update Submitted That Met QC Criteria: August 7, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Interferons; Ribavirin
• Other Study ID Numbers: AI452-030; 2012-003463-22 (EudraCT Number)