Hepatitis C, Genotype 1
Conditions
Brief summary
The purpose of this open label study is to evaluate the safety and efficacy of daclatasvir plus pegylated interferon-alfa 2a and ribavirin in untreated hepatitis C virus in patients coinfected with HIV
Interventions
DRUGDaclatasvir
Tablets; oral; 30, 60, or 90 mg; once daily; up to 24 weeks
DRUGRibavirin
Tablets; oral; for patients weighing \<75 kg, the total dose is 1000 mg per day (2 200-mg tablets in the morning and 3 200-mg tablets in the evening); for patients weighing \>75 kg, the total dose is 1200 mg per day (3 200-mg tablets in morning and 3 200-mg tablets in evening); twice daily with food; 24 or 48 weeks depending on response
Syringe, subcutaneous injection, 180 μg, once weekly, 24 or 48 weeks depending on response
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Key Inclusion Criteria: * Males and females, 18 to 70 years of age * Hepatitis C virus (HCV) genotype 1a or 1b * HCV-treatment naive * HCV RNA \>10,000 IU/mL at screening * HIV-1 infection (approximately 250 patients receiving highly active antiretroviral therapy \[HAART\], up to 50 patients not receiving HAART) * For patients receiving HAART, HIV RNA must be below \<40 copies/mL at screening and must be \<400 copies/ml for at least 6 months prior to screening Key
Exclusion criteria
* Patients receiving HAART who first initiated antiretroviral therapy within the last 6 months of Day 1 * Patients receiving HAART who have changed their antiretroviral regimen due to safety or efficacy associated to HIV treatment within the last 3 months prior to Day 1. However, if changes are required to a patient's HAART regimen to meet the requirements of the protocol, these changes are allowed at the screening visit. The patient should wait a minimum of 1 month prior to Day 1 after a repeat of HIV viral load has been confirmed, \<40 copies/ mL * Use of prohibited HAART regimens within 1 month of Day 1 and throughout the treatment period of the trial (patients receiving HAART who have changed their antiretroviral regimen to initiate any HCV treatment within 6 weeks prior to Day 1) * Laboratory values: 1. Neutrophil count \<1500 cells/μL (\<1200 cells/ μL for Blacks) 2. Platelet count \<90,000 cells/μL 3. Hemoglobin ≤12 g/dL for females, hemoglobin ≤13 g/dL for males 4. Total bilirubin ≥34 μmol/L (or ≥2 mg/dL) unless a patient has a documented history of Gilbert's disease or antiretroviral regimen contains atazanavir 5. Alanine aminotransferase ≥5\*upper limit of normal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) | Follow-up Week 12 | SVR12 was defined as hepatitis C virus (HCV) values lower than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy. SVR12 was defined as hepatitis C virus (HCV) values lower than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Week 1, 2, 4, 6, 8, 12 and at both Weeks 4 and 12; end of treatment; and follow-up Weeks 12 and 24 | Participants who achieved HCV RNA levels lower than the LLOQ i.e., 25 IU/ml, TD or TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy. |
| Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Week 1, 2, 4, 6, 8, and 12 and at both Weeks 4 and 12; end of treatment; and follow-up Weeks 12 and 24 | Participants who achieved HCV RNA levels lower than the LLOQ, TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy. |
| Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL | End of treatment (up to Week 48) | Participants who received HAART, maintained HIV RNA \<40 copies/mL, and experienced confirmed HIV RNA ≥ 400 copies/mL were determined. |
| Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | Follow-up Week 12 | Percentages calculated as number of responders/number who received treatment. |
| Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | From Day 1 to 7 days post last dose of study treatment (up to Week 48) | Adverse event was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threating, an important medical event, or a congenital anomaly/birth defect; or required prolonged hospitalization. HAART=highly active antiretroviral therapy. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, France, Germany, Italy, Puerto Rico, Russia, Spain, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 84 sites in 13 countries.
Pre-assignment details
Of 549 participants enrolled, 301 were randomized to receive treatment. Of the 248 participants who were not randomized, 204 no longer met study criteria, and 44 discontinued due to other reasons.
Participants by arm
| Arm | Count |
|---|---|
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg Participants taking HIV ritonavir-boosted protease inhibitors received daclatasvir tablets, 30 mg, orally once daily; peg-interferon alfa-2a (pegIFNalfa-2a) solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets, orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks. | 132 |
| HAART Therapy: Daclatasvir, 60 mg Participants taking other HAART, including rilpivirine, received daclatasvir tablets, 60 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks. | 39 |
| HAART: Daclatasvir, 30 mg + 60 mg Participants taking non-nucleoside reverse transcriptase inhibitors, except rilpivirine, received 2 daclatasvir tablets (1x30 mg and 1x60 mg), orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks. | 106 |
| Non-HAART Therapy: Daclatasvir, 60 mg Participants not receiving HAART received daclatasvir tablets, 60 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally, twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks. | 24 |
| Total | 301 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Follow-up Period | Death | 0 | 0 | 1 | 0 |
| Follow-up Period | Follow-up no longer required | 0 | 1 | 0 | 0 |
| Follow-up Period | Lost to Follow-up | 4 | 1 | 3 | 2 |
| Follow-up Period | Withdrawal by Subject | 3 | 0 | 3 | 1 |
| Treatment Period | Adverse Event | 7 | 3 | 6 | 1 |
| Treatment Period | Lack of Efficacy | 12 | 4 | 14 | 1 |
| Treatment Period | Lost to Follow-up | 1 | 2 | 2 | 0 |
| Treatment Period | Other | 1 | 0 | 0 | 0 |
| Treatment Period | Patient no Longer Meets Study Criteria | 1 | 0 | 0 | 0 |
| Treatment Period | Patient Requested Discontinue Study drug | 4 | 0 | 1 | 1 |
| Treatment Period | Withdrawal by Subject | 5 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | HAART Therapy: Daclatasvir, 60 mg | HAART: Daclatasvir, 30 mg + 60 mg | Non-HAART Therapy: Daclatasvir, 60 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 47 years STANDARD_DEVIATION 9.72 | 47.9 years STANDARD_DEVIATION 9.03 | 46.5 years STANDARD_DEVIATION 9.42 | 36 years STANDARD_DEVIATION 9.02 | 46.1 years STANDARD_DEVIATION 9.9 |
| Age, Customized 65 years and older | 7 participants | 0 participants | 2 participants | 0 participants | 9 participants |
| Age, Customized Younger than 65 years | 125 participants | 39 participants | 104 participants | 24 participants | 292 participants |
| Sex: Female, Male Female | 27 Participants | 7 Participants | 27 Participants | 11 Participants | 72 Participants |
| Sex: Female, Male Male | 105 Participants | 32 Participants | 79 Participants | 13 Participants | 229 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 122 / 132 | 38 / 39 | 100 / 106 | 23 / 24 |
| serious Total, serious adverse events | 12 / 132 | 6 / 39 | 6 / 106 | 0 / 24 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12)
SVR12 was defined as hepatitis C virus (HCV) values lower than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy. SVR12 was defined as hepatitis C virus (HCV) values lower than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy.
Time frame: Follow-up Week 12
Population: The analysis was performed in all participants who received at least 1 dose of study therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) | 75 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) | 71.8 Percentage of participants |
| HAART: Daclatasvir, 30 mg + 60 mg | Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) | 71.7 Percentage of participants |
| HAART Therapy: Daclatasvir 30 or 60 or 90 mg | Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) | 73.3 Percentage of participants |
| Non-HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) | 87.5 Percentage of participants |
Secondary
Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation
Adverse event was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threating, an important medical event, or a congenital anomaly/birth defect; or required prolonged hospitalization. HAART=highly active antiretroviral therapy.
Time frame: From Day 1 to 7 days post last dose of study treatment (up to Week 48)
Population: The analysis was performed in all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | Deaths | 0 Participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | Grade 3 to 4 AEs | 46 Participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | SAEs | 12 Participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | AEs leading to discontinuation | 7 Participants |
| HAART Therapy: Daclatasvir, 60 mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | AEs leading to discontinuation | 4 Participants |
| HAART Therapy: Daclatasvir, 60 mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | Grade 3 to 4 AEs | 12 Participants |
| HAART Therapy: Daclatasvir, 60 mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | Deaths | 1 Participants |
| HAART Therapy: Daclatasvir, 60 mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | SAEs | 6 Participants |
| HAART: Daclatasvir, 30 mg + 60 mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | Deaths | 0 Participants |
| HAART: Daclatasvir, 30 mg + 60 mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | AEs leading to discontinuation | 6 Participants |
| HAART: Daclatasvir, 30 mg + 60 mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | SAEs | 6 Participants |
| HAART: Daclatasvir, 30 mg + 60 mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | Grade 3 to 4 AEs | 35 Participants |
| HAART Therapy: Daclatasvir 30 or 60 or 90 mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | AEs leading to discontinuation | 17 Participants |
| HAART Therapy: Daclatasvir 30 or 60 or 90 mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | Deaths | 2 Participants |
| HAART Therapy: Daclatasvir 30 or 60 or 90 mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | SAEs | 24 Participants |
| HAART Therapy: Daclatasvir 30 or 60 or 90 mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | Grade 3 to 4 AEs | 93 Participants |
| Non-HAART Therapy: Daclatasvir, 60 mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | Grade 3 to 4 AEs | 4 Participants |
| Non-HAART Therapy: Daclatasvir, 60 mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | SAEs | 0 Participants |
| Non-HAART Therapy: Daclatasvir, 60 mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | AEs leading to discontinuation | 1 Participants |
| Non-HAART Therapy: Daclatasvir, 60 mg | Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | Deaths | 0 Participants |
Secondary
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND)
Participants who achieved HCV RNA levels lower than the LLOQ i.e., 25 IU/ml, TD or TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy.
Time frame: Week 1, 2, 4, 6, 8, 12 and at both Weeks 4 and 12; end of treatment; and follow-up Weeks 12 and 24
Population: The analysis was performed in all participants who received at least 1 dose of study therapy. On-treatment virologic response rates were not significantly different from one another among 30 mg, 60 mg, and 90 mg groups in the HAART cohort, thus these groups were combined as per pre-specified analysis plan.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Week 2 | 71.5 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Week 12 | 85.2 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Follow-up Week 24 | 70.4 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Weeks 4 and 12 | 78.7 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Week 6 | 84.1 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | End of treatment | 84.8 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Week 4 | 82.7 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Follow-up Week 12 | 73.3 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Week 8 | 84.1 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Week 1 | 39.7 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Follow-up Week 24 | 83.3 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Week 2 | 91.7 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Week 1 | 41.7 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Week 4 | 95.8 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Week 6 | 87.5 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Week 8 | 95.8 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Week 12 | 91.7 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Weeks 4 and 12 | 91.7 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | End of treatment | 95.8 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Follow-up Week 12 | 87.5 Percentage of participants |
Secondary
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND)
Participants who achieved HCV RNA levels lower than the LLOQ, TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy.
Time frame: Week 1, 2, 4, 6, 8, and 12 and at both Weeks 4 and 12; end of treatment; and follow-up Weeks 12 and 24
Population: The analysis was performed in all participants who received at least 1 dose of study therapy. On-treatment virologic response rates were not significantly different from one another among 30 mg, 60 mg, and 90 mg groups in the HAART cohort, thus these groups were combined as per pre-specified analysis plan.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Week 8 | 78 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Week 1 | 9 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Week 2 | 33.9 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Week 4 | 64.3 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Week 6 | 74.4 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Week 12 | 81.2 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Weeks 4 and 12 | 61.4 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | End of treatment | 84.8 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Follow-up Week 12 | 73.3 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Follow-up Week 24 | 70.4 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | End of treatment | 95.8 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Week 12 | 91.7 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Week 1 | 16.7 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Follow-up Week 24 | 83.3 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Week 2 | 50 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Weeks 4 and 12 | 87.5 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Week 4 | 91.7 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Follow-up Week 12 | 87.5 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Week 6 | 87.5 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Week 8 | 95.8 Percentage of participants |
Secondary
Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL
Participants who received HAART, maintained HIV RNA \<40 copies/mL, and experienced confirmed HIV RNA ≥ 400 copies/mL were determined.
Time frame: End of treatment (up to Week 48)
Population: The analysis was performed in all participants who received at least 1 dose of study therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL | HIV RNA <40 copies/mL | 88.6 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL | HIV RNA ≥400 copies/mL | 0.0 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL | HIV RNA ≥400 copies/mL | 2.6 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL | HIV RNA <40 copies/mL | 89.7 Percentage of participants |
| HAART: Daclatasvir, 30 mg + 60 mg | Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL | HIV RNA ≥400 copies/mL | 0.0 Percentage of participants |
| HAART: Daclatasvir, 30 mg + 60 mg | Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL | HIV RNA <40 copies/mL | 93.4 Percentage of participants |
| HAART Therapy: Daclatasvir 30 or 60 or 90 mg | Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL | HIV RNA ≥400 copies/mL | 0.4 Percentage of participants |
| HAART Therapy: Daclatasvir 30 or 60 or 90 mg | Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL | HIV RNA <40 copies/mL | 90.6 Percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene
Percentages calculated as number of responders/number who received treatment.
Time frame: Follow-up Week 12
Population: The analysis was performed in all participants who received at least 1 dose of study therapy. Here 'n' signifies number of participants evaluable at the specified time-point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | Not reported (n=2, 0, 5, 7, 1) | 100.0 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | TT Genotype (n=22, 3, 12, 37, 2) | 68.2 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | CC Genotype (n=36, 14, 39, 89, 6) | 94.4 Percentage of participants |
| Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | CT Genotype (n=72, 22, 50,144, 15) | 66.7 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | TT Genotype (n=22, 3, 12, 37, 2) | 33.3 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | CC Genotype (n=36, 14, 39, 89, 6) | 92.9 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | CT Genotype (n=72, 22, 50,144, 15) | 63.6 Percentage of participants |
| HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | Not reported (n=2, 0, 5, 7, 1) | 0.0 Percentage of participants |
| HAART: Daclatasvir, 30 mg + 60 mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | TT Genotype (n=22, 3, 12, 37, 2) | 58.3 Percentage of participants |
| HAART: Daclatasvir, 30 mg + 60 mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | CC Genotype (n=36, 14, 39, 89, 6) | 79.5 Percentage of participants |
| HAART: Daclatasvir, 30 mg + 60 mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | Not reported (n=2, 0, 5, 7, 1) | 60.0 Percentage of participants |
| HAART: Daclatasvir, 30 mg + 60 mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | CT Genotype (n=72, 22, 50,144, 15) | 70.0 Percentage of participants |
| HAART Therapy: Daclatasvir 30 or 60 or 90 mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | CT Genotype (n=72, 22, 50,144, 15) | 67.4 Percentage of participants |
| HAART Therapy: Daclatasvir 30 or 60 or 90 mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | CC Genotype (n=36, 14, 39, 89, 6) | 87.6 Percentage of participants |
| HAART Therapy: Daclatasvir 30 or 60 or 90 mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | TT Genotype (n=22, 3, 12, 37, 2) | 62.2 Percentage of participants |
| HAART Therapy: Daclatasvir 30 or 60 or 90 mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | Not reported (n=2, 0, 5, 7, 1) | 71.4 Percentage of participants |
| Non-HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | TT Genotype (n=22, 3, 12, 37, 2) | 50.0 Percentage of participants |
| Non-HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | CC Genotype (n=36, 14, 39, 89, 6) | 100.0 Percentage of participants |
| Non-HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | CT Genotype (n=72, 22, 50,144, 15) | 93.3 Percentage of participants |
| Non-HAART Therapy: Daclatasvir, 60 mg | Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | Not reported (n=2, 0, 5, 7, 1) | 0.0 Percentage of participants |