Hepatitis C Virus
Conditions
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
Interventions
BIOLOGICALPegylated-Interferon-lambda
DRUGRibavirin
DRUGDaclatasvir
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Sustained Virologic Response (SVR12) at Follow-Up Week 12 | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Early Virologic Response (cEVR) | Treatment Week 12 | 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) | End of the treatment (Week 12 for Cohort A, Week 24 for Cohort B) | 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) | Follow-up Week 24 | 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 Rapid Virologic Response (RVR) | Treatment Week 4 | RVR was defined as HCV RNA less than the lower limit of quantitation, target not detected at Week 4. |
| Percentage of Participants With Flu-Like Symptoms and Musculoskeletal Symptoms On-Treatment | After day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B) | 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 | From Day 1 to end of follow-up (maximum of 60 weeks for Cohort A and 72 weeks for Cohort B) | 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 | After day 1 to to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B) | 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. |
| Percentage of Participants With Treatment-Emergent Cytopenic Abnormalities On-Treatment | After day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B) | 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. |
Countries
Australia, France, Italy, Netherlands, Romania, Russia, Spain, United States
Participant flow
Pre-assignment details
A total of 71 participants were enrolled, of which 51 subjects were randomized and treated.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A Participants with HCV GT-2 or GT-3 infection (Cohort A) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily; peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, orally, twice daily (a total 800 mg per day) for 12 weeks treatment, 12 weeks and a maximum of 12 weeks, respectively (treatment period= 12 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks). | 12 |
| Cohort B Participants with HCV GT-1b or GT-4 infection (Cohort B) were treated with Lambda/Ribavirin/Daclatasvir. Participants were administered daclatasvir 60 mg orally, once daily, peginterferon lambda-1a 180 microgram subcutaneous injection, once weekly and ribavirin tablets, twice daily, orally, based on weight (participants weighing \<75 kg = 1000 mg and participants weighing \>=75 kg = 1200 mg per day) for 12 weeks treatment, 24 weeks and a maximum of 24 weeks, respectively (treatment period= 24 Weeks). Participants were followed up for 24 weeks after administration of last treatment (follow-up period= 24 Weeks). | 39 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up Period (24 Weeks) | Other than specified | 0 | 1 |
| Follow-up Period (24 Weeks) | Withdrawal by Subject | 1 | 1 |
| Treatment Period | Adverse event, non-fatal | 1 | 3 |
| Treatment Period | Lack of Efficacy | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort A | Cohort B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 38 Participants | 50 Participants |
| Age, Continuous | 42.8 years STANDARD_DEVIATION 9.94 | 45.2 years STANDARD_DEVIATION 12.04 | 44.6 years STANDARD_DEVIATION 11.53 |
| HCV Genotype Genotype 1A | 0 Participants | 0 Participants | 0 Participants |
| HCV Genotype Genotype 1B | 0 Participants | 39 Participants | 39 Participants |
| HCV Genotype Genotype 2 | 2 Participants | 0 Participants | 2 Participants |
| HCV Genotype Genotype 3 | 10 Participants | 0 Participants | 10 Participants |
| HCV Genotype Genotype 4 | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 39 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 39 |
| other Total, other adverse events | 10 / 12 | 36 / 39 |
| serious Total, serious adverse events | 0 / 12 | 4 / 39 |
Outcome results
Primary
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.
Time frame: Follow-up Week 12
Population: The analysis was performed in modified intent to treat (mITT) population defined as participants meeting the response criteria over all treated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A | Percentage of Participants Who Achieved Sustained Virologic Response (SVR12) at Follow-Up Week 12 | 91.7 Percentage of participants |
| Cohort B | Percentage of Participants Who Achieved Sustained Virologic Response (SVR12) at Follow-Up Week 12 | 89.7 Percentage of participants |
Secondary
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.
Time frame: After day 1 to to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)
Population: All treated participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A | Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities | ALT | 2 Participants |
| Cohort A | Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities | PT | 0 Participants |
| Cohort A | Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities | INR | 0 Participants |
| Cohort A | Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities | Bilirubin | 2 Participants |
| Cohort A | Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities | AST | 0 Participants |
| Cohort A | Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities | Triglycerides | 0 Participants |
| Cohort B | Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities | Triglycerides | 1 Participants |
| Cohort B | Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities | INR | 1 Participants |
| Cohort B | Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities | ALT | 1 Participants |
| Cohort B | Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities | AST | 2 Participants |
| Cohort B | Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities | PT | 1 Participants |
| Cohort B | Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities | Bilirubin | 7 Participants |
Secondary
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.
Time frame: From Day 1 to end of follow-up (maximum of 60 weeks for Cohort A and 72 weeks for Cohort B)
Population: All treated participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death | AEs on treatment | 10 Percentage of participants |
| Cohort A | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death | SAEs | 0 Percentage of participants |
| Cohort A | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death | Death | 0 Percentage of participants |
| Cohort A | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death | AE leading to discontinuation | 1 Percentage of participants |
| Cohort A | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death | Dose reduction - Lambda | 0 Percentage of participants |
| Cohort A | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death | Dose reduction - RBV | 0 Percentage of participants |
| Cohort B | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death | Dose reduction - Lambda | 1 Percentage of participants |
| Cohort B | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death | AEs on treatment | 38 Percentage of participants |
| Cohort B | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death | AE leading to discontinuation | 3 Percentage of participants |
| Cohort B | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death | SAEs | 4 Percentage of participants |
| Cohort B | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death | Dose reduction - RBV | 2 Percentage of participants |
| Cohort B | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death | Death | 0 Percentage of participants |
Secondary
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.
Time frame: Treatment Week 12
Population: mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A | Percentage of Participants With Complete Early Virologic Response (cEVR) | 91.7 Percentage of participants |
| Cohort B | Percentage of Participants With Complete Early Virologic Response (cEVR) | 92.3 Percentage of participants |
Secondary
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.
Time frame: End of the treatment (Week 12 for Cohort A, Week 24 for Cohort B)
Population: mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A | Percentage of Participants With End of the Treatment Response (EOTR) | 100 Percentage of participants |
| Cohort B | Percentage of Participants With End of the Treatment Response (EOTR) | 100 Percentage of participants |
Secondary
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.
Time frame: After day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)
Population: mITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A | Percentage of Participants With Flu-Like Symptoms and Musculoskeletal Symptoms On-Treatment | Flu-like symptoms | 8.3 Percentage of participants |
| Cohort A | Percentage of Participants With Flu-Like Symptoms and Musculoskeletal Symptoms On-Treatment | Musculoskeletal symptoms | 0 Percentage of participants |
| Cohort B | Percentage of Participants With Flu-Like Symptoms and Musculoskeletal Symptoms On-Treatment | Flu-like symptoms | 12.8 Percentage of participants |
| Cohort B | Percentage of Participants With Flu-Like Symptoms and Musculoskeletal Symptoms On-Treatment | Musculoskeletal symptoms | 15.4 Percentage of participants |
Secondary
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.
Time frame: Treatment Week 4
Population: mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A | Percentage of Participants With Rapid Virologic Response (RVR) | 91.7 Percentage of participants |
| Cohort B | Percentage of Participants With Rapid Virologic Response (RVR) | 76.9 Percentage of participants |
Secondary
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.
Time frame: Follow-up Week 24
Population: mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A | Percentage of Participants With Sustained Virologic Response at Follow-Up Week 24 (SVR24) | 66.7 Percentage of participants |
| Cohort B | Percentage of Participants With Sustained Virologic Response at Follow-Up Week 24 (SVR24) | 30.8 Percentage of participants |
Secondary
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.
Time frame: After day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)
Population: mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A | Percentage of Participants With Treatment-Emergent Cytopenic Abnormalities On-Treatment | 0 Percentage of participants |
| Cohort B | Percentage of Participants With Treatment-Emergent Cytopenic Abnormalities On-Treatment | 0 Percentage of participants |