Chronic Hepatitis C
Conditions
Brief summary
The purpose of the study is to determine whether therapy with the combination of PSI-7977 and daclatasvir (BMS-790052) with or without ribavirin is effective in treating hepatitis C virus (HCV) infection when given for 12 or 24 weeks as measured by sustained virologic response with undetectable HCV RNA 12 weeks post treatment
Interventions
DRUGPSI-7977
Tablets, oral, 400 mg, once daily
DRUGDaclatasvir
Tablets, oral, 60 mg, once daily
DRUGRibavirin
Tablets, oral, 200 mg
Sponsors
Pharmasset
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Men and women, ages 18 to 70 years. * Participants infected with hepatitis C virus (HCV) genotype 1, 2, or 3, with no previous exposure to an interferon formulation (ie, interferon-alpha, pegylated interferon-alpha) ribavirin, or other HCV-specific direct-acting antiviral (including daclatasvir and PSI-7977). * Patients should have chronic hepatitis C genotype 1a, 1b, 2, or 3 as documented by: positive test results for anti-HCV antibody; HCV RNA; or a HCV genotype at least 6 months prior to screening, and HCV RNA and anti-HCV antibody at the time of screening.
Exclusion criteria
* Evidence of a medical condition associate with chronic liver disease other than HCV. * History of variceal bleeding, hepatic encephalopathy, or ascites requiring management with diuretics or paracentesis. * History of hemophilia. * History of torsade de pointes. * Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment. * History of gastrointestinal disease or surgical procedure (except cholecystectomy). * History of clinically significant cardiac disease. * Blood transfusion within 4 weeks prior to study drug administration. * Poor venous access. * Any other medical, psychiatric, and/or social reason which, in the opinion of the Investigator, would make the candidate inappropriate for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response at Post Treatment Week 12 (SVR12) | Follow-up Week 12 | SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target detected or target not detected (ie, HCV RNA \<25 IU/mL) at follow-up Week 12. DCV=daclatasvir, SOF=sofosbuvir. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Viral Breakthrough During the Treatment Period | First dose of study drug (Day 1) up to end of treatment period (up to 12 or 24 weeks, depending on treatment group) | Viral breakthrough is defined as any confirmed increase in viral load ≥1 log from nadir or any confirmed hepatitis C virus RNA levels ≥25 IU/mL on or after Week 8. |
| Percentage of Participants Who Experienced Viral Relapse During Follow-up Period | Day 1 of follow-up period (Week 13 or 25, depending on treatment group) to end of follow-up period (up to 48 weeks) | Viral relapse during follow-up is defined as any confirmed quantifiable hepatitis C virus (HCV) RNA ≥25 IU/mL with HCV RNA levels less than the lower limit of quantitation, target detected or target not detected, ie, HCV RNA \<25 IU/mL at the end of treatment. |
| Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24) | Follow-up Week 24 | SVR24 was defined as participant's hepatitis C virus RNA less than the lower limit of quantitation, target detected or target not detected at follow-up Week 24. DCV=daclatasvir, SOF=sofosbuvir. |
| Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | First dose of study drug (Day 1) up to the start of rescue therapy (12 or 24 weeks, depending on treatment group) | AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting 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-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Based on the severity, AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Very severe. |
| Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up Period | AEs: From Day 1 of follow-up period (Week 13 or 25) up to study discharge (up to 72 weeks). SAEs: From Day 1 of follow-up period (Week 13 or 25) up to 30 days after study discharge (up to 74 weeks) | AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting 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-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Based on the severity, AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Very severe |
| Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Baseline, Follow-up week 24 | Change from baseline in log10 HCV RNA at scheduled sampling time. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
The study was conducted at 18 centres in 2 countries.
Pre-assignment details
A total of 350 participants were enrolled, and 211 were randomized and received study drug.
Participants by arm
| Arm | Count |
|---|---|
| Treatment A: Sofosbuvir + Daclatasvir Participants with hepatitis C virus genotype 1a or 1b received sofosbuvir, 400 mg, once daily for 7 days and then added daclatasvir, 60 mg, once daily for 24 weeks. | 15 |
| Treatment: Sofosbuvir + Daclatasvir Participants with genotype 2 or 3 received sofosbuvir, 400 mg, once daily for 7 days and then added daclatasvir, 60 mg, once daily for 24 weeks. | 16 |
| Treatment C: Sofosbuvir + Daclatasvir Participants with genotype 1a or 1b received sofosbuvir, 400 mg, once daily and daclatasvir, 60 mg, once daily for 24 weeks. | 14 |
| Treatment D: Sofosbuvir + Daclatasvir Participants with genotype-2 or -3 received sofosbuvir, 400 mg, once daily and daclatasvir, 60 mg, once daily for 24 weeks.. | 14 |
| Treatment E: Sofosbuvir +Daclatasvir + Ribavirin Participants with genotype 1a or 1b received sofosbuvir, 400 mg, once daily; daclatasvir, 60 mg, once daily for 24 weeks; and ribavirin in a total daily dose of 1000 mg (2 200-mg tablets AM and 3 200-mg tablets PM) for participants weighing \<75 kg and a total daily dose of 1200 mg (3 200-mg tablets AM and 3 200-mg tablets PM) for participants weighing ≥75 kg for 24 weeks. | 15 |
| Treatment F: Sofosbuvir + Daclatasvir + Ribavirin Participants with genotype 2 or 3 received sofosbuvir, 400 mg, once daily; daclatasvir, 60 mg, once daily for 24 weeks; and ribavarin in total daily dose of 800 mg (2 200-mg tablets AM and 2 200-mg tablets PM) for 24 weeks. | 14 |
| Treatment G: Sofosbuvir + Daclatasvir Participants with genotype1 a or 1b received sofosbuvir, 400 mg, once daily and daclatasvir, 60 mg, once daily for 12 weeks.. | 41 |
| Treatment H: Sofosbuvir +Daclatasvir + Ribavirin Participants with genotype 1a or 1b received sofosbuvir, 400 mg, once daily, daclatasvir, 60 mg, once daily for 12 weeks and ribavirin (in a total daily dose of 1000 mg (2 200-mg tablets AM and 3 200-mg tablets PM for participants weighing \<75 kg and a total daily dose of 1200 mg (3 200-mg tablets AM and 3 200-mg tablets PM for participants weighing ≥ 75 kg) for 12 weeks. | 41 |
| Treatment I: Sofosbuvir + Daclatasvir Participants with genotype 1a or 1b who experienced telaprevir/boceprevir treatment failure received sofosbuvir, 400 mg once daily and daclatasvir, 60 mg, once daily for 24 weeks. | 21 |
| Treatment J: Sofosbuvir +Daclatasvir +Ribavirin Participants with genotype 1a or 1b who experienced telaprevir/boceprevir treatment failure received sofosbuvir, 400 mg once daily, daclatasvir, 60 mg, once daily for 24 weeks and ribavarin in a total daily dose of 1000 mg (2 200-mg tablets AM and 3 200-mg tablets PM for participants weighing \<75 kg) and a total daily dose of 1200 mg (3 200-mg tablets AM and 3 200-mg tablets PM for participants weighing ≥75 kg) for 24 weeks. | 20 |
| Total | 211 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Follow-up Period | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 |
| Follow-up Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Treatment Period | Adverse Event | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Treatment Period | Lack of Efficacy | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Treatment A: Sofosbuvir + Daclatasvir | Treatment: Sofosbuvir + Daclatasvir | Treatment C: Sofosbuvir + Daclatasvir | Treatment D: Sofosbuvir + Daclatasvir | Treatment E: Sofosbuvir +Daclatasvir + Ribavirin | Treatment F: Sofosbuvir + Daclatasvir + Ribavirin | Treatment G: Sofosbuvir + Daclatasvir | Treatment H: Sofosbuvir +Daclatasvir + Ribavirin | Treatment I: Sofosbuvir + Daclatasvir | Treatment J: Sofosbuvir +Daclatasvir +Ribavirin | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 52.1 years STANDARD_DEVIATION 10.18 | 50.6 years STANDARD_DEVIATION 8.53 | 52.7 years STANDARD_DEVIATION 7.39 | 49.7 years STANDARD_DEVIATION 10.49 | 50.9 years STANDARD_DEVIATION 11.72 | 48.8 years STANDARD_DEVIATION 12.27 | 50.9 years STANDARD_DEVIATION 11.56 | 53.1 years STANDARD_DEVIATION 9.53 | 56.6 years STANDARD_DEVIATION 9.89 | 52.6 years STANDARD_DEVIATION 10.89 | 52.0 years STANDARD_DEVIATION 10.37 |
| Age, Customized <65 years | 15 participants | 15 participants | 14 participants | 13 participants | 15 participants | 13 participants | 39 participants | 38 participants | 18 participants | 19 participants | 199 participants |
| Age, Customized >= 65 years | 0 participants | 1 participants | 0 participants | 1 participants | 0 participants | 1 participants | 2 participants | 3 participants | 3 participants | 1 participants | 12 participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 5 Participants | 8 Participants | 8 Participants | 9 Participants | 21 Participants | 20 Participants | 8 Participants | 8 Participants | 100 Participants |
| Sex: Female, Male Male | 7 Participants | 11 Participants | 9 Participants | 6 Participants | 7 Participants | 5 Participants | 20 Participants | 21 Participants | 13 Participants | 12 Participants | 111 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 16 | 0 / 14 | 0 / 14 | 0 / 15 | 0 / 14 | 0 / 41 | 0 / 41 | 0 / 21 | 0 / 20 |
| serious Total, serious adverse events | 2 / 15 | 0 / 16 | 2 / 14 | 3 / 14 | 2 / 15 | 2 / 14 | 1 / 41 | 1 / 41 | 0 / 21 | 2 / 20 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response at Post Treatment Week 12 (SVR12)
SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target detected or target not detected (ie, HCV RNA \<25 IU/mL) at follow-up Week 12. DCV=daclatasvir, SOF=sofosbuvir.
Time frame: Follow-up Week 12
Population: The analysis was performed in all treated participants who received at least 1 dose of active study therapy. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment-naive Participants With Genotype 1 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 12 (SVR12) | DCV/SOF without ribavirin (n=70, 30, 21) | 100.0 Percentage of participants |
| Treatment-naive Participants With Genotype 1 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 12 (SVR12) | DCV/SOF with ribavirin (n=56, 14, 20) | 96.4 Percentage of participants |
| Treatment-naive Participants With Genotype 1 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 12 (SVR12) | DCF/SOF All | 98.4 Percentage of participants |
| Treatment-naive Participants With Genotype 2 or 3 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 12 (SVR12) | DCV/SOF without ribavirin (n=70, 30, 21) | 93.3 Percentage of participants |
| Treatment-naive Participants With Genotype 2 or 3 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 12 (SVR12) | DCV/SOF with ribavirin (n=56, 14, 20) | 85.7 Percentage of participants |
| Treatment-naive Participants With Genotype 2 or 3 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 12 (SVR12) | DCF/SOF All | 90.9 Percentage of participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 12 (SVR12) | DCV/SOF with ribavirin (n=56, 14, 20) | 95.0 Percentage of participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 12 (SVR12) | DCF/SOF All | 97.6 Percentage of participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 12 (SVR12) | DCV/SOF without ribavirin (n=70, 30, 21) | 100.0 Percentage of participants |
Secondary
Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24
Change from baseline in log10 HCV RNA at scheduled sampling time.
Time frame: Baseline, Follow-up week 24
Population: The analysis was performed in all treated participants who received at least 1 dose of active study therapy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment-naive Participants With Genotype 1 | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Change at Follow-up week 24 | -5.19 IU/mL | Standard Deviation 1.478 |
| Treatment-naive Participants With Genotype 1 | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Baseline | 1.28 IU/mL | Standard Deviation 1.258 |
| Treatment-naive Participants With Genotype 2 or 3 | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Baseline | 0.95 IU/mL | Standard Deviation 0 |
| Treatment-naive Participants With Genotype 2 or 3 | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Change at Follow-up week 24 | -5.23 IU/mL | Standard Deviation 1.601 |
| Telaprevir or Boceprevir Failures With Genotype 1 | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Baseline | 0.95 IU/mL | Standard Deviation 0 |
| Telaprevir or Boceprevir Failures With Genotype 1 | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Change at Follow-up week 24 | -5.67 IU/mL | Standard Deviation 0.336 |
| Treatment D: Sofosbuvir + Daclatasvir | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Change at Follow-up week 24 | -5.83 IU/mL | Standard Deviation 0.509 |
| Treatment D: Sofosbuvir + Daclatasvir | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Baseline | 0.98 IU/mL | Standard Deviation 0.114 |
| Treatment E: Sofosbuvir + Daclatasvir + Ribavirin | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Baseline | 0.95 IU/mL | Standard Deviation 0 |
| Treatment E: Sofosbuvir + Daclatasvir + Ribavirin | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Change at Follow-up week 24 | -5.77 IU/mL | Standard Deviation 0.583 |
| Treatment F: Sofosbuvir + Daclatasvir + Ribavirin | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Change at Follow-up week 24 | -5.61 IU/mL | Standard Deviation 0.61 |
| Treatment F: Sofosbuvir + Daclatasvir + Ribavirin | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Baseline | 0.95 IU/mL | Standard Deviation 0 |
| Treatment G: Sofosbuvir + Daclatasvir | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Change at Follow-up week 24 | -5.19 IU/mL | Standard Deviation 0.49 |
| Treatment G: Sofosbuvir + Daclatasvir | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Baseline | 0.95 IU/mL | Standard Deviation 0 |
| Treatment H: Sofosbuvir + Daclatasvir + Ribavirin | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Change at Follow-up week 24 | -5.48 IU/mL | Standard Deviation 0.576 |
| Treatment H: Sofosbuvir + Daclatasvir + Ribavirin | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Baseline | 0.95 IU/mL | Standard Deviation 0 |
| Treatment I: Sofosbuvir + Daclatasvir | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Baseline | 0.95 IU/mL | Standard Deviation 0 |
| Treatment I: Sofosbuvir + Daclatasvir | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Change at Follow-up week 24 | -5.39 IU/mL | Standard Deviation 0.386 |
| Treatment J: Sofosbuvir + Daclatasvir + Ribavirin | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Change at Follow-up week 24 | -5.36 IU/mL | Standard Deviation 0.38 |
| Treatment J: Sofosbuvir + Daclatasvir + Ribavirin | Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24 | Baseline | 0.95 IU/mL | Standard Deviation 0 |
Secondary
Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy
AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting 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-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Based on the severity, AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Very severe.
Time frame: First dose of study drug (Day 1) up to the start of rescue therapy (12 or 24 weeks, depending on treatment group)
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment-naive Participants With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Deaths | 0 Participants |
| Treatment-naive Participants With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | SAEs | 1 Participants |
| Treatment-naive Participants With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | AEs leading to discontinuation | 0 Participants |
| Treatment-naive Participants With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Phosporus | 3 Participants |
| Treatment-naive Participants With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Fasting serum glucose | 0 Participants |
| Treatment-naive Participants With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Serum glucose | 0 Participants |
| Treatment-naive Participants With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Total cholesterol | 1 Participants |
| Treatment-naive Participants With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Uric acid | 1 Participants |
| Treatment-naive Participants With Genotype 2 or 3 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Serum glucose | 2 Participants |
| Treatment-naive Participants With Genotype 2 or 3 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Fasting serum glucose | 1 Participants |
| Treatment-naive Participants With Genotype 2 or 3 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | SAEs | 6 Participants |
| Treatment-naive Participants With Genotype 2 or 3 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Uric acid | 0 Participants |
| Treatment-naive Participants With Genotype 2 or 3 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Total cholesterol | 0 Participants |
| Treatment-naive Participants With Genotype 2 or 3 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Phosporus | 1 Participants |
| Treatment-naive Participants With Genotype 2 or 3 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | AEs leading to discontinuation | 1 Participants |
| Treatment-naive Participants With Genotype 2 or 3 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Deaths | 0 Participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Total cholesterol | 0 Participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | AEs leading to discontinuation | 0 Participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Phosporus | 0 Participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Fasting serum glucose | 1 Participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Serum glucose | 0 Participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Uric acid | 0 Participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Deaths | 0 Participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | SAEs | 1 Participants |
| Treatment D: Sofosbuvir + Daclatasvir | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | AEs leading to discontinuation | 1 Participants |
| Treatment D: Sofosbuvir + Daclatasvir | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Phosporus | 1 Participants |
| Treatment D: Sofosbuvir + Daclatasvir | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | SAEs | 7 Participants |
| Treatment D: Sofosbuvir + Daclatasvir | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Deaths | 0 Participants |
| Treatment D: Sofosbuvir + Daclatasvir | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Fasting serum glucose | 2 Participants |
| Treatment D: Sofosbuvir + Daclatasvir | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Uric acid | 0 Participants |
| Treatment D: Sofosbuvir + Daclatasvir | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Total cholesterol | 1 Participants |
| Treatment D: Sofosbuvir + Daclatasvir | Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy | Gr 3 Serum glucose | 1 Participants |
Secondary
Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up Period
AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting 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-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Based on the severity, AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Very severe
Time frame: AEs: From Day 1 of follow-up period (Week 13 or 25) up to study discharge (up to 72 weeks). SAEs: From Day 1 of follow-up period (Week 13 or 25) up to 30 days after study discharge (up to 74 weeks)
Population: All participants who received at least 1 dose of study drug and entered follow-up period
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment-naive Participants With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up Period | Deaths | 0 Participants |
| Treatment-naive Participants With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up Period | Grade 3-4 Lab Abnormalities: Serum glucose | 1 Participants |
| Treatment-naive Participants With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up Period | SAEs | 2 Participants |
| Treatment-naive Participants With Genotype 2 or 3 | Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up Period | Deaths | 0 Participants |
| Treatment-naive Participants With Genotype 2 or 3 | Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up Period | Grade 3-4 Lab Abnormalities: Serum glucose | 0 Participants |
| Treatment-naive Participants With Genotype 2 or 3 | Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up Period | SAEs | 4 Participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up Period | SAEs | 2 Participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up Period | Deaths | 0 Participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up Period | Grade 3-4 Lab Abnormalities: Serum glucose | 0 Participants |
| Treatment D: Sofosbuvir + Daclatasvir | Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up Period | Deaths | 0 Participants |
| Treatment D: Sofosbuvir + Daclatasvir | Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up Period | Grade 3-4 Lab Abnormalities: Serum glucose | 0 Participants |
| Treatment D: Sofosbuvir + Daclatasvir | Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up Period | SAEs | 4 Participants |
Secondary
Percentage of Participants Who Experienced Viral Relapse During Follow-up Period
Viral relapse during follow-up is defined as any confirmed quantifiable hepatitis C virus (HCV) RNA ≥25 IU/mL with HCV RNA levels less than the lower limit of quantitation, target detected or target not detected, ie, HCV RNA \<25 IU/mL at the end of treatment.
Time frame: Day 1 of follow-up period (Week 13 or 25, depending on treatment group) to end of follow-up period (up to 48 weeks)
Population: The analysis was performed in all treated participants who received at least 1 dose of active study therapy. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment-naive Participants With Genotype 1 | Percentage of Participants Who Experienced Viral Relapse During Follow-up Period | DCV/SOF with ribavirin (n=56, 14, 20) | 0 Percentage of participants |
| Treatment-naive Participants With Genotype 1 | Percentage of Participants Who Experienced Viral Relapse During Follow-up Period | DCV/SOF without ribavirin (n=70, 30, 21) | 1.4 Percentage of participants |
| Treatment-naive Participants With Genotype 2 or 3 | Percentage of Participants Who Experienced Viral Relapse During Follow-up Period | DCV/SOF with ribavirin (n=56, 14, 20) | 0 Percentage of participants |
| Treatment-naive Participants With Genotype 2 or 3 | Percentage of Participants Who Experienced Viral Relapse During Follow-up Period | DCV/SOF without ribavirin (n=70, 30, 21) | 3.3 Percentage of participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Percentage of Participants Who Experienced Viral Relapse During Follow-up Period | DCV/SOF with ribavirin (n=56, 14, 20) | 0 Percentage of participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Percentage of Participants Who Experienced Viral Relapse During Follow-up Period | DCV/SOF without ribavirin (n=70, 30, 21) | 0 Percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24)
SVR24 was defined as participant's hepatitis C virus RNA less than the lower limit of quantitation, target detected or target not detected at follow-up Week 24. DCV=daclatasvir, SOF=sofosbuvir.
Time frame: Follow-up Week 24
Population: The analysis was performed in all treated participants who received at least 1 dose of active study therapy. Here the 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment-naive Participants With Genotype 1 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24) | DCV/SOF All | 95.2 Percentage of participants |
| Treatment-naive Participants With Genotype 1 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24) | DCV/SOF with ribavirin (n=56, 14, 20) | 94.6 Percentage of participants |
| Treatment-naive Participants With Genotype 1 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24) | DCV/SOF without ribavirin (n=70, 30, 21) | 95.7 Percentage of participants |
| Treatment-naive Participants With Genotype 2 or 3 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24) | DCV/SOF without ribavirin (n=70, 30, 21) | 93.3 Percentage of participants |
| Treatment-naive Participants With Genotype 2 or 3 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24) | DCV/SOF All | 93.2 Percentage of participants |
| Treatment-naive Participants With Genotype 2 or 3 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24) | DCV/SOF with ribavirin (n=56, 14, 20) | 92.9 Percentage of participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24) | DCV/SOF with ribavirin (n=56, 14, 20) | 100.0 Percentage of participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24) | DCV/SOF All | 100.0 Percentage of participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24) | DCV/SOF without ribavirin (n=70, 30, 21) | 100.0 Percentage of participants |
Secondary
Percentage of Participants With Viral Breakthrough During the Treatment Period
Viral breakthrough is defined as any confirmed increase in viral load ≥1 log from nadir or any confirmed hepatitis C virus RNA levels ≥25 IU/mL on or after Week 8.
Time frame: First dose of study drug (Day 1) up to end of treatment period (up to 12 or 24 weeks, depending on treatment group)
Population: The analysis was performed in all treated participants who received at least 1 dose of active study therapy. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment-naive Participants With Genotype 1 | Percentage of Participants With Viral Breakthrough During the Treatment Period | DCV/SOF with ribavirin (n=56, 14, 20) | 0 Percentage of participants |
| Treatment-naive Participants With Genotype 1 | Percentage of Participants With Viral Breakthrough During the Treatment Period | DCV/SOF without ribavirin (n=70, 30, 21) | 0 Percentage of participants |
| Treatment-naive Participants With Genotype 2 or 3 | Percentage of Participants With Viral Breakthrough During the Treatment Period | DCV/SOF with ribavirin (n=56, 14, 20) | 0 Percentage of participants |
| Treatment-naive Participants With Genotype 2 or 3 | Percentage of Participants With Viral Breakthrough During the Treatment Period | DCV/SOF without ribavirin (n=70, 30, 21) | 3.3 Percentage of participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Percentage of Participants With Viral Breakthrough During the Treatment Period | DCV/SOF with ribavirin (n=56, 14, 20) | 0 Percentage of participants |
| Telaprevir or Boceprevir Failures With Genotype 1 | Percentage of Participants With Viral Breakthrough During the Treatment Period | DCV/SOF without ribavirin (n=70, 30, 21) | 0 Percentage of participants |