Hepatitis C Virus
Conditions
Brief summary
To identify a shorter duration of antiviral therapy (12 or 16 weeks) for the combination of daclatasvir with pegylated interferon alfa-2a and ribavirin.
Interventions
DRUGPlacebo
Tablets, oral, 0 mg, once daily, for 24 weeks
DRUGDaclatasvir
Tablets, oral, 60 mg, once daily, for 12, 16, or 24 weeks
DRUGPegylated interferon alfa-2a
Solution for injection, subcutaneous injection, 180 µg/0.5 mL, once weekly, for 12, 16, or 24 weeks
DRUGRibavirin
Tablets, oral, 800 mg, twice daily, for 12, 16, or 24 weeks
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participants chronically infected with hepatitis C virus (HCV) genotype 2 or 3 * No previous exposure to an interferon formulation (ie, interferon alfa, pegylated interferon alfa-2a ) or ribavirin * Body mass index (BMI) of 18 to 35 kg/m\^2, inclusive. BMI=weight (kg)/height (m)\^2 * Males and females, 18 - 70 years of age Key
Exclusion criteria
* Liver transplant recipients * Documented or suspected hepatocellular carcinoma * Evidence of decompensated cirrhosis * History of chronic hepatitis B virus (HBV). Patients with resolved HBV infection may participate * Current or known history of cancer * Any gastrointestinal disease or surgical procedure that may impact the absorption of study drug * Inability to tolerate oral medication * Poor venous access * Severe psychiatric disease * History of chronic pulmonary disease * History of cardiomyopathy, coronary artery disease (including angina), interventive procedure for coronary artery disease (including angioplasty, stent procedure, or cardiac bypass surgery), ventricular arrhythmia,, or other clinically significant cardiac disease * History of or current electrocardiogram findings indicative of cardiovascular instability * Preexisting ophthalmologic disorders considered clinically significant on eye * History of uncontrolled diabetes mellitus * Any known contraindication to pegylated interferon alfa-2a or ribavirin not otherwise specified. * Positive hepatitis B virus surface antigen, HIV-1 or HIV-2 Ab * Prior exposure to any HCV direct antiviral agent (eg, HCV protease, polymerase, previous nonstructural protein 5A inhibitors) * Exposure to any investigational drug or placebo
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 2 | Follow-up Week 24 | SVR24 was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at follow-up Week 24. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. |
| Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 3 | Follow-up Week 24 | SVR24 was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at follow-up Week 24. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 2 | Week 12 | cEVR was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at Week 12. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. |
| Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 3 | Week 12 | cEVR was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at Week 12. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. |
| Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 2 | Follow-up Week 12 | SVR12 was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at follow-up Week 12. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. |
| Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 3 | Follow-up Week 12 | SVR12 was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at follow-up Week 12. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. |
| Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 2 | Week 4 | RVR was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at Week 4. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. |
| Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 | Baseline up to Week 48 | Virologic failure was defined as: 1. Virologic breakthrough: confirmed \>1 log10 increase in HCV RNA over nadir or confirmed RNA ≥lower limit of quantitation (LLOQ) after confirmed HCV RNA \<LLOQ, target not detected (TND) while on treatment 2. \<1 log10 decrease in HCV RNA from baseline at Week 4 of treatment 3. Failure to achieve early virologic response: \<2 log10 decrease in HCV RNA from baseline and HCV RNA ≥LLOQ at Week 12 of treatment 4. HCV RNA ≥LLOQ or \<LLOQ, target detected (TD) at the end of treatment (EOT) (including early discontinuation) 5. Relapse, defined as HCV RNA ≥LLOQ or \<LLOQ, TD during follow-up, after HCV RNA \<LLOQ, TND at EOT. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. |
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | Baseline (Day 1) up to 24 weeks (treatment period) | AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not has 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-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Treatment-related AE was defined as an AE that had certain, probable, possible, or unknown relationship to study drug. Mild (Grade 1): awareness of event but easily tolerated; Moderate (Grade 2): discomfort enough to cause some interference with usual activity; Severe (Grade 3): inability to carry out usual activity; Very severe (Grade 4): debilitating, significantly incapacitates participant despite symptomatic therapy. Only Grade 2-4 treatment-related AEs were reported. |
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died During Follow-up Period | From end of treatment period up to Week 48 (follow-up period) | AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not has 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-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. |
| Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 | Baseline up to Week 48 | Virologic failure was defined as: 1. Virologic breakthrough: confirmed \>1 log10 increase in HCV RNA over nadir or confirmed RNA ≥lower limit of quantitation (LLOQ) after confirmed HCV RNA \<LLOQ, target not detected (TND) while on treatment 2. \<1 log10 decrease in HCV RNA from baseline at Week 4 of treatment 3. Failure to achieve early virologic response: \<2 log10 decrease in HCV RNA from baseline and HCV RNA ≥LLOQ at Week 12 of treatment 4. HCV RNA ≥LLOQ or \<LLOQ, target detected (TD) at the end of treatment (EOT) (including early discontinuation) 5. Relapse, defined as HCV RNA ≥LLOQ or \<LLOQ, TD during follow-up, after HCV RNA \<LLOQ, TND at EOT. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. |
| Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 3 | Week 4 | RVR was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at Week 4. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. |
Countries
Australia, Canada, Denmark, France, Italy, United States
Participant flow
Pre-assignment details
A total of 196 participants were enrolled, of which 152 participants were randomized; remaining 44 participants did not meet study criteria. Of randomized participants:151 were treated; 1 participant withdrew consent.
Participants by arm
| Arm | Count |
|---|---|
| Dacalatasvir, 60 mg, 12-Week Cohort Participants received daclatasvir tablets 60 mg orally, once daily, with pegylated-interferon alfa-2a (pegIFNα-2a) solution for injection 180 µg/0.5 mL subcutaneously, once weekly, and ribavirin tablets 400 mg orally, twice daily, up to 12 weeks. | 50 |
| Daclatasvir, 60 mg, 16-Week Cohort Participants received daclatasvir tablets 60 mg orally, once daily, with pegIFNα-2a solution for injection 180 µg/0.5 mL subcutaneously, once weekly, and ribavirin tablets 400 mg orally, twice daily, up to 16 weeks. | 50 |
| Placebo Participants received placebo matching with daclatasvir tablets orally, once daily, with pegIFNα-2a solution for injection 180 µg/0.5 mL subcutaneously, once weekly, and ribavirin tablets 400 mg orally, twice daily, up to 24 weeks. | 51 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Follow-up Period (up to Week 48) | Lost to Follow-up | 1 | 4 | 4 |
| Follow-up Period (up to Week 48) | Other | 0 | 0 | 5 |
| Follow-up Period (up to Week 48) | Withdrawal by Subject | 0 | 2 | 1 |
| Treatment Period (up to Week 24) | Adverse Event | 3 | 1 | 2 |
| Treatment Period (up to Week 24) | Lack of Efficacy | 0 | 1 | 3 |
| Treatment Period (up to Week 24) | Lost to Follow-up | 0 | 2 | 0 |
| Treatment Period (up to Week 24) | Participant's request to discontinue | 1 | 2 | 2 |
| Treatment Period (up to Week 24) | Poor compliance/noncompliance | 0 | 0 | 1 |
| Treatment Period (up to Week 24) | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Daclatasvir, 60 mg, 16-Week Cohort | Dacalatasvir, 60 mg, 12-Week Cohort | Placebo |
|---|---|---|---|---|
| Age, Continuous | 47.9 years STANDARD_DEVIATION 9.09 | 47.5 years STANDARD_DEVIATION 9.2 | 47.5 years STANDARD_DEVIATION 8.42 | 48.8 years STANDARD_DEVIATION 9.73 |
| Cirrhosis Status Absent | 127 participants | 43 participants | 43 participants | 41 participants |
| Cirrhosis Status Not Reported | 5 participants | 3 participants | 0 participants | 2 participants |
| Cirrhosis Status Present | 19 participants | 4 participants | 7 participants | 8 participants |
| HCV RNA Distribution <800,000 IU/mL | 25 participants | 7 participants | 12 participants | 6 participants |
| HCV RNA Distribution ≥800,000 IU/mL | 126 participants | 43 participants | 38 participants | 45 participants |
| Hepatitis C Virus (HCV) RNA (IU/mL) | 6.5 Log10 IU/mL STANDARD_DEVIATION 0.69 | 6.6 Log10 IU/mL STANDARD_DEVIATION 0.62 | 6.4 Log10 IU/mL STANDARD_DEVIATION 0.82 | 6.6 Log10 IU/mL STANDARD_DEVIATION 0.59 |
| Randomization Stratum HCV Genotype 2 | 71 participants | 23 participants | 24 participants | 24 participants |
| Randomization Stratum HCV Genotype 3 | 80 participants | 27 participants | 26 participants | 27 participants |
| Sex: Female, Male Female | 55 Participants | 13 Participants | 18 Participants | 24 Participants |
| Sex: Female, Male Male | 96 Participants | 37 Participants | 32 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 49 / 50 | 49 / 50 | 48 / 51 | 0 / 49 | 0 / 47 | 0 / 49 |
| serious Total, serious adverse events | 4 / 50 | 0 / 50 | 3 / 51 | 2 / 49 | 0 / 47 | 0 / 49 |
Outcome results
Primary
Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 2
SVR24 was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at follow-up Week 24. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time frame: Follow-up Week 24
Population: All treated participants with hepatitis C virus genotype 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclatasvir, 60 mg, 12-Week Cohort | Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 2 | 83.3 percentage of participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 2 | 82.6 percentage of participants |
| Placebo | Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 2 | 62.5 percentage of participants |
80% CI: [4.9, 36.8]
80% CI: [3.9, 36.3]
Primary
Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 3
SVR24 was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at follow-up Week 24. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time frame: Follow-up Week 24
Population: All treated participants with HCV genotype 3.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclatasvir, 60 mg, 12-Week Cohort | Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 3 | 69.2 percentage of participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 3 | 66.7 percentage of participants |
| Placebo | Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 3 | 59.3 percentage of participants |
80% CI: [-6.8, 26.7]
80% CI: [-9.4, 24.2]
Secondary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died During Follow-up Period
AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not has 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-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization.
Time frame: From end of treatment period up to Week 48 (follow-up period)
Population: All follow-up participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daclatasvir, 60 mg, 12-Week Cohort | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died During Follow-up Period | SAEs | 2 participants |
| Daclatasvir, 60 mg, 12-Week Cohort | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died During Follow-up Period | AEs | 16 participants |
| Daclatasvir, 60 mg, 12-Week Cohort | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died During Follow-up Period | Deaths | 0 participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died During Follow-up Period | SAEs | 0 participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died During Follow-up Period | AEs | 12 participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died During Follow-up Period | Deaths | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died During Follow-up Period | AEs | 11 participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died During Follow-up Period | Deaths | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died During Follow-up Period | SAEs | 0 participants |
Secondary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period
AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not has 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-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Treatment-related AE was defined as an AE that had certain, probable, possible, or unknown relationship to study drug. Mild (Grade 1): awareness of event but easily tolerated; Moderate (Grade 2): discomfort enough to cause some interference with usual activity; Severe (Grade 3): inability to carry out usual activity; Very severe (Grade 4): debilitating, significantly incapacitates participant despite symptomatic therapy. Only Grade 2-4 treatment-related AEs were reported.
Time frame: Baseline (Day 1) up to 24 weeks (treatment period)
Population: All treated participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daclatasvir, 60 mg, 12-Week Cohort | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | AEs | 49 participants |
| Daclatasvir, 60 mg, 12-Week Cohort | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | Discontinuations due to AEs | 4 participants |
| Daclatasvir, 60 mg, 12-Week Cohort | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | SAEs | 4 participants |
| Daclatasvir, 60 mg, 12-Week Cohort | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | Grade 2-4 Treatment-related AEs | 27 participants |
| Daclatasvir, 60 mg, 12-Week Cohort | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | Deaths | 0 participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | Grade 2-4 Treatment-related AEs | 22 participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | AEs | 49 participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | Discontinuations due to AEs | 3 participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | SAEs | 0 participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | Deaths | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | SAEs | 3 participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | Grade 2-4 Treatment-related AEs | 30 participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | Deaths | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | AEs | 50 participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | Discontinuations due to AEs | 2 participants |
Secondary
Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2
Virologic failure was defined as: 1. Virologic breakthrough: confirmed \>1 log10 increase in HCV RNA over nadir or confirmed RNA ≥lower limit of quantitation (LLOQ) after confirmed HCV RNA \<LLOQ, target not detected (TND) while on treatment 2. \<1 log10 decrease in HCV RNA from baseline at Week 4 of treatment 3. Failure to achieve early virologic response: \<2 log10 decrease in HCV RNA from baseline and HCV RNA ≥LLOQ at Week 12 of treatment 4. HCV RNA ≥LLOQ or \<LLOQ, target detected (TD) at the end of treatment (EOT) (including early discontinuation) 5. Relapse, defined as HCV RNA ≥LLOQ or \<LLOQ, TD during follow-up, after HCV RNA \<LLOQ, TND at EOT. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time frame: Baseline up to Week 48
Population: All treated participants with HCV genotype 2. Here, n signifies the number of participants evaluable for the respective category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daclatasvir, 60 mg, 12-Week Cohort | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 | Virologic breakthrough (n=24,23,24) | 0 participants |
| Daclatasvir, 60 mg, 12-Week Cohort | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 | HCV RNA ≥LLOQ or <LLOQ, TD at EOT (n=24,23,24) | 1 participants |
| Daclatasvir, 60 mg, 12-Week Cohort | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 | <1 log10 decrease in HCV RNA at Week4 (n=24,23,24) | 0 participants |
| Daclatasvir, 60 mg, 12-Week Cohort | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 | Relapse (n=23,21,22) | 1 participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 | Relapse (n=23,21,22) | 0 participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 | <1 log10 decrease in HCV RNA at Week4 (n=24,23,24) | 1 participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 | HCV RNA ≥LLOQ or <LLOQ, TD at EOT (n=24,23,24) | 2 participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 | Virologic breakthrough (n=24,23,24) | 1 participants |
| Placebo | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 | Relapse (n=23,21,22) | 2 participants |
| Placebo | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 | Virologic breakthrough (n=24,23,24) | 1 participants |
| Placebo | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 | <1 log10 decrease in HCV RNA at Week4 (n=24,23,24) | 0 participants |
| Placebo | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 | HCV RNA ≥LLOQ or <LLOQ, TD at EOT (n=24,23,24) | 1 participants |
Secondary
Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3
Virologic failure was defined as: 1. Virologic breakthrough: confirmed \>1 log10 increase in HCV RNA over nadir or confirmed RNA ≥lower limit of quantitation (LLOQ) after confirmed HCV RNA \<LLOQ, target not detected (TND) while on treatment 2. \<1 log10 decrease in HCV RNA from baseline at Week 4 of treatment 3. Failure to achieve early virologic response: \<2 log10 decrease in HCV RNA from baseline and HCV RNA ≥LLOQ at Week 12 of treatment 4. HCV RNA ≥LLOQ or \<LLOQ, target detected (TD) at the end of treatment (EOT) (including early discontinuation) 5. Relapse, defined as HCV RNA ≥LLOQ or \<LLOQ, TD during follow-up, after HCV RNA \<LLOQ, TND at EOT. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time frame: Baseline up to Week 48
Population: All treated participants with HCV genotype 3. Here, n signifies the number of participants evaluable for the respective category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daclatasvir, 60 mg, 12-Week Cohort | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 | Relapse (n=25,24,21) | 6 participants |
| Daclatasvir, 60 mg, 12-Week Cohort | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 | <1 log10 decrease in HCV RNA at Week4 (n=26,27,27) | 0 participants |
| Daclatasvir, 60 mg, 12-Week Cohort | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 | HCV RNA ≥LLOQ or <LLOQ, TD at EOT (n=26,27,27) | 1 participants |
| Daclatasvir, 60 mg, 12-Week Cohort | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 | Virologic breakthrough (n=26,27,27) | 0 participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 | <1 log10 decrease in HCV RNA at Week4 (n=26,27,27) | 1 participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 | HCV RNA ≥LLOQ or <LLOQ, TD at EOT (n=26,27,27) | 2 participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 | Virologic breakthrough (n=26,27,27) | 0 participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 | Relapse (n=25,24,21) | 6 participants |
| Placebo | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 | HCV RNA ≥LLOQ or <LLOQ, TD at EOT (n=26,27,27) | 3 participants |
| Placebo | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 | Virologic breakthrough (n=26,27,27) | 1 participants |
| Placebo | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 | Relapse (n=25,24,21) | 3 participants |
| Placebo | Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 | <1 log10 decrease in HCV RNA at Week4 (n=26,27,27) | 3 participants |
Secondary
Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 2
cEVR was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at Week 12. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time frame: Week 12
Population: All treated participants with HCV genotype 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclatasvir, 60 mg, 12-Week Cohort | Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 2 | 91.7 percentage of participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 2 | 82.6 percentage of participants |
| Placebo | Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 2 | 75.0 percentage of participants |
Secondary
Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 3
cEVR was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at Week 12. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time frame: Week 12
Population: All treated participants with HCV genotype 3.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclatasvir, 60 mg, 12-Week Cohort | Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 3 | 80.8 percentage of participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 3 | 88.9 percentage of participants |
| Placebo | Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 3 | 59.3 percentage of participants |
Secondary
Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 2
RVR was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at Week 4. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time frame: Week 4
Population: All treated participants with HCV genotype 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclatasvir, 60 mg, 12-Week Cohort | Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 2 | 87.5 percentage of participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 2 | 73.9 percentage of participants |
| Placebo | Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 2 | 41.7 percentage of participants |
Secondary
Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 3
RVR was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at Week 4. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time frame: Week 4
Population: All treated participants with HCV genotype 3.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclatasvir, 60 mg, 12-Week Cohort | Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 3 | 84.6 percentage of participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 3 | 74.1 percentage of participants |
| Placebo | Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 3 | 37.0 percentage of participants |
Secondary
Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 2
SVR12 was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at follow-up Week 12. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time frame: Follow-up Week 12
Population: All treated participants with HCV genotype 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclatasvir, 60 mg, 12-Week Cohort | Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 2 | 87.5 percentage of participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 2 | 82.6 percentage of participants |
| Placebo | Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 2 | 70.8 percentage of participants |
Secondary
Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 3
SVR12 was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at follow-up Week 12. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time frame: Follow-up Week 12
Population: All treated participants with HCV genotype 3.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclatasvir, 60 mg, 12-Week Cohort | Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 3 | 69.2 percentage of participants |
| Daclatasvir, 60 mg, 16-Week Cohort | Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 3 | 77.8 percentage of participants |
| Placebo | Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 3 | 51.9 percentage of participants |