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

Primary Purpose

Hepatitis C Virus

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Pegylated-Interferon-lambda
Ribavirin
Daclatasvir
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C Virus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Stanford Boswell Clinic
  • Rush University Medical Center
  • Hospital Of The University Of Pennsylvania
  • Clinical Research Centers Of America
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort A: Genotype-2,-3 (Lambda/RBV/DCV)

Cohort B: Genotype-1b,-4 (Lambda/RBV/DCV)

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
December 3, 2012
Last Updated
August 7, 2020
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT01741545
Brief Title
Safety and Efficacy Study in Subjects With Chronic HCV and Underlying Hemophilia
Acronym
MAGNITUDE
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
March 31, 2013 (Actual)
Primary Completion Date
January 31, 2015 (Actual)
Study Completion Date
January 31, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C Virus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
71 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort A: Genotype-2,-3 (Lambda/RBV/DCV)
Arm Type
Experimental
Arm Description
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
Arm Title
Cohort B: Genotype-1b,-4 (Lambda/RBV/DCV)
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
Pegylated-Interferon-lambda
Other Intervention Name(s)
pegIFNλ, BMS-914143
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Intervention Type
Drug
Intervention Name(s)
Daclatasvir
Other Intervention Name(s)
BMS-790052
Primary Outcome Measure Information:
Title
Percentage of Participants Who Achieved Sustained Virologic Response (SVR12) at Follow-Up Week 12
Description
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.
Time Frame
Follow-up Week 12
Secondary Outcome Measure Information:
Title
Percentage of Participants With Rapid Virologic Response (RVR)
Description
RVR was defined as HCV RNA less than the lower limit of quantitation, target not detected at Week 4.
Time Frame
Treatment Week 4
Title
Percentage of Participants With Complete Early Virologic Response (cEVR)
Description
cEVR was defined as HCV RNA less than the lower limit of quantitation, target not detected at Week 12.
Time Frame
Treatment Week 12
Title
Percentage of Participants With End of the Treatment Response (EOTR)
Description
EOTR was defined as HCV RNA less than the lower limit of quantitation, target not detected at end of treatment.
Time Frame
End of the treatment (Week 12 for Cohort A, Week 24 for Cohort B)
Title
Percentage of Participants With Sustained Virologic Response at Follow-Up Week 24 (SVR24)
Description
SVR24 was defined as HCV RNA less than the lower limit of quantitation, target detected or target not detected at follow-up week 24.
Time Frame
Follow-up Week 24
Title
Percentage of Participants With Treatment-Emergent Cytopenic Abnormalities On-Treatment
Description
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.
Time Frame
After day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)
Title
Percentage of Participants With Flu-Like Symptoms and Musculoskeletal Symptoms On-Treatment
Description
Flu-like symptoms were defined as pyrexia or chills or pain. Musculoskeletal symptoms were defined as arthralgia or myalgia or back pain.
Time Frame
After day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)
Title
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death
Description
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.
Time Frame
From Day 1 to end of follow-up (maximum of 60 weeks for Cohort A and 72 weeks for Cohort B)
Title
Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities
Description
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.
Time Frame
After day 1 to to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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
Stanford Boswell Clinic
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Hospital Of The University Of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Clinical Research Centers Of America
City
Murray
State/Province
Utah
ZIP/Postal Code
84123
Country
United States
Facility Name
Local Institution
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Local Institution
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Local Institution
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Local Institution
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Local Institution
City
Herston
ZIP/Postal Code
4029
Country
Australia
Facility Name
Local Institution
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Local Institution
City
Lyon Cedex 04
ZIP/Postal Code
69317
Country
France
Facility Name
Local Institution
City
Montpellier Cedex 5
ZIP/Postal Code
34295
Country
France
Facility Name
Local Institution
City
Paris Cedex 13
ZIP/Postal Code
75651
Country
France
Facility Name
Local Institution
City
Paris Cedex 14
ZIP/Postal Code
75679
Country
France
Facility Name
Local Institution
City
Vandoeuvre Les Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
Local Institution
City
Firenze
ZIP/Postal Code
50134
Country
Italy
Facility Name
Local Institution
City
Milan
ZIP/Postal Code
20122
Country
Italy
Facility Name
Local Institution
City
Roma
ZIP/Postal Code
00185
Country
Italy
Facility Name
Local Institution
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Local Institution
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Local Institution
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
Facility Name
Local Institution
City
Rotterdam
ZIP/Postal Code
3015 CE
Country
Netherlands
Facility Name
Local Institution
City
Utrecht
ZIP/Postal Code
3508 GA
Country
Netherlands
Facility Name
Local Institution
City
Bucuresti
ZIP/Postal Code
50524
Country
Romania
Facility Name
Local Institution
City
Constanta
ZIP/Postal Code
900635
Country
Romania
Facility Name
Local Institution
City
Iasi
ZIP/Postal Code
700116
Country
Romania
Facility Name
Local Institution
City
Iasi
ZIP/Postal Code
700506
Country
Romania
Facility Name
Local Institution
City
Moscow
ZIP/Postal Code
107996
Country
Russian Federation
Facility Name
Local Institution
City
Saint Petersburg
ZIP/Postal Code
191186
Country
Russian Federation
Facility Name
Local Institution
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Local Institution
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Local Institution
City
Sevilla
ZIP/Postal Code
41013
Country
Spain

12. IPD Sharing Statement

Links:
URL
http://www.bms.com/studyconnect/Pages/home.aspx
Description
BMS clinical trial educational resource

Learn more about this trial

Safety and Efficacy Study in Subjects With Chronic HCV and Underlying Hemophilia

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