Hepatitis C
Conditions
Keywords
Hepatitis C Virus
Brief summary
The purpose of this study is to compare the effectiveness of BMS-790052 (Daclatasvir) and Telaprevir when given in combination with Peginterferon alfa-2a and Ribavirin in genotype 1b patients
Detailed description
Allocation: Randomized Stratified
Interventions
DRUGDaclatasvir
Film-coated tablet, oral, 60 mg, once daily, 24 weeks
DRUGTelaprevir
Film-coated tablet, oral, 750 mg, 3 times daily
DRUGPeginterferon alfa-2a
Solution for injection, subcutaneous injection, 180 μg, weekly
DRUGRibavirin
Film-coated tablet, oral, in a body weight stratified dose range of 1000-1200 mg per day
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participants chronically infected with hepatitis C virus (HCV) genotype 1a or 1b * HCV RNA viral load ≥10,000 IU/mL * No prior treatment including but not limited to interferon, ribavirin, and direct-acting antivirals * No history of cirrhosis liver biopsy within 3 years or Fibroscan® within 1 year * Body mass index of 18 to 35 kg/m\^2 * Negative for HIV and hepatitis B virus Key
Exclusion criteria
* Evidence of decompensated liver disease * Evidence of medical condition other than HCV contributing to chronic liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Genotype 1b Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) | Week 12 (Follow-up period) | SVR12 was defined as hepatitis C virus RNA levels to be lower than the limit of quantitation, ie, 25 IU/mL target detected or target not detected at follow-up Week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Genotype 1b Participants With Rapid Virologic Response (RVR) at Week 4 | Week 4 | RVR was defined as hepatitis c virus RNA levels lower than lower limit of quantitation, ie, 25 IU/mL target not detected at Week 4 of treatment. |
| Percentage of Genotype 1b Participants With Extended Rapid Virologic Response (eRVR) at Both Week 4 and Week 12 | Week 4, Week 12 | eRVR was defined as hepatitis C virus RNA levels lower than the lower limit of quantitation, ie, 25 IU/mL target not detected at both Weeks 4 and 12 of treatment. |
| Percentage of Genotype 1b Participants With Complete Early Virologic Response (cEVR) | Week 12 | cEVR was defined as hepatitis C virus RNA levels lower than the lower limit of quantitation, ie, 25 IU/mL target not detected at Week 12 of treatment. |
| Percentage of Genotype 1b Participants With Sustained Virologic Response at Follow-up Week 24 (SVR24) | Week 24 (Follow-up period) | SVR24 was defined as hepatitis C virus RNA levels lower than the lower limit of quantitation, ie, 25 IU/mL target detected or target not detected at follow-up week 24 of treatment. |
| Percentage of Genotype 1a Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) | Week 12 (Follow-up period) | SVR12 was defined as hepatitis C virus RNA levels lower than the lower limit of quantitation, ie, 25 IU/mL target detected or target not detected at follow-up week 12 of treatment. |
Countries
Argentina, Australia, Austria, Brazil, Canada, Denmark, France, Germany, Israel, Italy, Poland, Russia, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
A total of 793 participants were recruited at 90 sites in 15 countries.
Pre-assignment details
Of the 793 participants, 605 were randomized to treatment. A total of 191 enrolled subjects did not enter the treatment period as they no longer met study entry criteria and a 602 participants were received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Daclatasvir + PEG-IFN Alpha-2a + Ribavirin Participants received daclatasvir 60-mg tablet orally once daily for 24 weeks in combination with pegylated interferon alpha-2a (PEG-IFN alpha-2a)180 µg administered subcutaneously once a week for 24 or 48 weeks and ribavarin administered in a body weight stratified dose range of 1000-1200 mg per day (for participants weighing less than 75 kg, the total dose was 1000 mg per day and for those weighing greater than or equal to 75 kg, the dose was 1200 mg per day). | 402 |
| Telaprevir + PEG-IFN Alpha-2a + Ribavirin Participants received 2 telaprevir 375-mg tablets orally 3 times a day for 12 weeks. PEG-IFN alpha-2a 180 µg was coadministered subcutaneously once a week for 24 or 48 weeks depending on response, and ribavirin in a body weight stratified dose range of 1000-1200 mg per day was administered twice daily with food. | 200 |
| Total | 602 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-Up | Death | 1 | 0 |
| Follow-Up | Lost to Follow-up | 12 | 6 |
| Follow-Up | Other | 4 | 2 |
| Follow-Up | Participant Withdrew Consent | 6 | 1 |
| Follow-Up | Protocol Requires no Follow-Up | 2 | 1 |
| Treatment | Adverse Event | 25 | 25 |
| Treatment | Death | 0 | 1 |
| Treatment | Lack of Efficacy | 38 | 5 |
| Treatment | Lost to Follow-up | 9 | 4 |
| Treatment | Other | 1 | 0 |
| Treatment | Participant does not meet study criteria | 1 | 0 |
| Treatment | Participant withdrew consent | 1 | 2 |
| Treatment | Poor compliance/noncompliance | 1 | 0 |
| Treatment | Subject requested discontinue study drug | 7 | 3 |
Baseline characteristics
| Characteristic | Daclatasvir + PEG-IFN Alpha-2a + Ribavirin | Telaprevir + PEG-IFN Alpha-2a + Ribavirin | Total |
|---|---|---|---|
| Age, Continuous | 46.5 years STANDARD_DEVIATION 12.12 | 47.6 years STANDARD_DEVIATION 12.29 | 46.9 years STANDARD_DEVIATION 12.18 |
| Age, Customized 65 years and older | 15 participants | 12 participants | 27 participants |
| Age, Customized Younger than 65 years | 387 participants | 188 participants | 575 participants |
| Sex: Female, Male Female | 145 Participants | 81 Participants | 226 Participants |
| Sex: Female, Male Male | 257 Participants | 119 Participants | 376 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 384 / 402 | 193 / 200 |
| serious Total, serious adverse events | 26 / 402 | 20 / 200 |
Outcome results
Primary
Percentage of Genotype 1b Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12)
SVR12 was defined as hepatitis C virus RNA levels to be lower than the limit of quantitation, ie, 25 IU/mL target detected or target not detected at follow-up Week 12.
Time frame: Week 12 (Follow-up period)
Population: The analysis was performed in all treated participants who received at least 1 dose of active study therapy. Here, 'Number of participants analysed' signifies Genotype 1b participants assessed for SVR12 response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclatasvir + PEG-IFN Alpha-2a + Ribavirin | Percentage of Genotype 1b Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) | 85.1 Percentage of participants |
| Telaprevir + PEG-IFN Alpha-2a + Ribavirin | Percentage of Genotype 1b Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) | 81.3 Percentage of participants |
Comparison: Percentage difference between SVR12 rate in the experimental and control arms was computed using a stratum-adjusted Mantel-Haenszel confidence interval (95% level) for the difference in rates. The stratification factors were IL28B rs1297860 single nucleotide polymorphism (CC or non-CC) and baseline cirrhosis status (absent or present), unless otherwise indicated.95% CI: [-3.3, 11.9]Stratum-adjusted Mantel-Haenszel
Secondary
Percentage of Genotype 1a Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12)
SVR12 was defined as hepatitis C virus RNA levels lower than the lower limit of quantitation, ie, 25 IU/mL target detected or target not detected at follow-up week 12 of treatment.
Time frame: Week 12 (Follow-up period)
Population: The analysis was performed in all treated participants who received at least 1 dose of active study therapy. Here, 'Number of participants analysed' signifies Genotype 1a participants assessed for SVR12 response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclatasvir + PEG-IFN Alpha-2a + Ribavirin | Percentage of Genotype 1a Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) | 64.9 Percentage of participants |
| Telaprevir + PEG-IFN Alpha-2a + Ribavirin | Percentage of Genotype 1a Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) | 69.7 Percentage of participants |
Secondary
Percentage of Genotype 1b Participants With Complete Early Virologic Response (cEVR)
cEVR was defined as hepatitis C virus RNA levels lower than the lower limit of quantitation, ie, 25 IU/mL target not detected at Week 12 of treatment.
Time frame: Week 12
Population: The analysis was performed in all treated participants who received at least 1 dose of active study therapy. Here, 'Number of participants analysed' signifies Genotype 1b participants assessed for cEVR response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclatasvir + PEG-IFN Alpha-2a + Ribavirin | Percentage of Genotype 1b Participants With Complete Early Virologic Response (cEVR) | 90.7 percentage of participants |
| Telaprevir + PEG-IFN Alpha-2a + Ribavirin | Percentage of Genotype 1b Participants With Complete Early Virologic Response (cEVR) | 90.03 percentage of participants |
Secondary
Percentage of Genotype 1b Participants With Extended Rapid Virologic Response (eRVR) at Both Week 4 and Week 12
eRVR was defined as hepatitis C virus RNA levels lower than the lower limit of quantitation, ie, 25 IU/mL target not detected at both Weeks 4 and 12 of treatment.
Time frame: Week 4, Week 12
Population: The analysis was performed in all treated participants who received at least 1 dose of active study therapy. Here, 'Number of participants analysed' signifies Genotype 1b participants assessed for eRVR response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclatasvir + PEG-IFN Alpha-2a + Ribavirin | Percentage of Genotype 1b Participants With Extended Rapid Virologic Response (eRVR) at Both Week 4 and Week 12 | 75.0 Percentage of participants |
| Telaprevir + PEG-IFN Alpha-2a + Ribavirin | Percentage of Genotype 1b Participants With Extended Rapid Virologic Response (eRVR) at Both Week 4 and Week 12 | 73.1 Percentage of participants |
Secondary
Percentage of Genotype 1b Participants With Rapid Virologic Response (RVR) at Week 4
RVR was defined as hepatitis c virus RNA levels lower than lower limit of quantitation, ie, 25 IU/mL target not detected at Week 4 of treatment.
Time frame: Week 4
Population: The analysis was performed in all treated participants who received at least 1 dose of active study therapy. Here, 'Number of participants analysed' signifies Genotype 1b participants assessed for RVR response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclatasvir + PEG-IFN Alpha-2a + Ribavirin | Percentage of Genotype 1b Participants With Rapid Virologic Response (RVR) at Week 4 | 77.2 Percentage of participants |
| Telaprevir + PEG-IFN Alpha-2a + Ribavirin | Percentage of Genotype 1b Participants With Rapid Virologic Response (RVR) at Week 4 | 79.1 Percentage of participants |
Secondary
Percentage of Genotype 1b Participants With Sustained Virologic Response at Follow-up Week 24 (SVR24)
SVR24 was defined as hepatitis C virus RNA levels lower than the lower limit of quantitation, ie, 25 IU/mL target detected or target not detected at follow-up week 24 of treatment.
Time frame: Week 24 (Follow-up period)
Population: The analysis was performed in all treated participants who received at least 1 dose of active study therapy. Here, 'Number of participants analysed' signifies Genotype 1b participants assessed for SVR24 response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclatasvir + PEG-IFN Alpha-2a + Ribavirin | Percentage of Genotype 1b Participants With Sustained Virologic Response at Follow-up Week 24 (SVR24) | 84.3 Percentage of participants |
| Telaprevir + PEG-IFN Alpha-2a + Ribavirin | Percentage of Genotype 1b Participants With Sustained Virologic Response at Follow-up Week 24 (SVR24) | 80.6 Percentage of participants |