Hepatitis C
Conditions
Brief summary
This trial was open to participants who had received a liver transplant or had cirrhosis due to chronic HCV. All subjects were treated with daclatasvir+sofosbuvir+ribavirin and were followed for 24 weeks post treatment. Under certain conditions, the treatment duration could have been extended for cirrhotic participants. The study tested the efficacy and safety of this combination for treatment of HCV in cirrhotic and post transplant patients.
Interventions
DRUGDaclatasvir
DRUGSofosbuvir
DRUGRibavirin
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Participants must be able to understand and agree to comply with the prescribed dosing regimens and procedures, report for regularly scheduled study visits, and reliably communicate with study personnel about adverse events and concomitant medications * Participants chronically infected with hepatitis C virus (HCV) Genotype 1, 2, 3, 4, 5, or 6 with HCV RNA viral load of ≥10,000 IU/mL at screening * Participants may be treatment-naïve or treatment-experienced * Cirrhotic participants must have cirrhosis confirmed by biopsy, Fibroscan or fibrotest and Aspartate aminotransferase platelet ratio index (APRI) criteria as outlined in the protocol * Post-transplant participants must be at least 3 months post-transplant with no evidence of moderate or severe rejection
Exclusion criteria
* History of multi-organ transplant, with the exception of dual transplantation of the liver/kidney, is prohibited * Current or known history of cancer (with the following exceptions: In situ carcinoma of the cervix, adequately treated basal or squamous cell carcinoma of the skin, or hepatocellular carcinoma within Milan criteria for transplantation) within 5 years prior to screening * Evidence of an ongoing medical condition contributing to chronic liver disease other than HCV (such as, but not limited to: hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, or toxin exposures) * History of HIV infection or chronic hepatitis B virus (HBV) as documented by HBV serologies (e.g., HBsAg-seropositive). Participants with resolved HBV infection may participate (e.g., HBcAb-seropositive with concurrent HBsAg-seronegative) * Active hospitalization for decompensated liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of HCV Genotype-1 Infected Post-liver Transplanted Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) | Post-treatment follow-up Week 12 | SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation (\<LLOQ) i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window. |
| Percentage of Genotype-1 Infected Cirrhotic Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) | Post-treatment follow-up Week 12 | SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment | Week 1, 2, 4, 6, 8, 12, End of treatment | Participants who responded to treatment were assessed using proportion of subjects with hepatitis C Virus RNA levels below the lower limit of quantitation i.e., 25 IU/mL target not detected, at each on-treatment visit. |
| Percentage of Participants With CC or Non-CC Genotype Who Achieved Sustained Virologic Response at 12 Weeks After the Last Dose of Study Drug (SVR12) | Post-treatment follow-up Week 12 | Participants categorized into 2 genotypes (CC and non-CC) based on single nucleotide polymorphism in the IL28B gene were assessed for SVR12, defined as response in which hepatitis C virus RNA levels be \<lower limit of quantitation ie, 25 IU/mL or below 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. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window. |
| Percentage of Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6 | Post-treatment follow-up Week 12 | SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window. |
| Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | From start of study treatment up to 7 days post last dose of study treatment | Grade 3-4 laboratory abnormalities were defined as: Hemoglobin as 6.50-7.4 g/dL for grade 3 and/or \< 6.5 g/dL for grade 4, Platelet count as 25\*10\^9-50\*10\^9 /L for grade 3 and/or \< 25.000\*10\^9 /L for grade 4, International normalized ratio as 2.1-3.0\*upper limit of normal (ULN) \> 3.0\*ULN for grade 3 and/or \> 3.0\*ULN for grade 4, Leukocytes as 1.0\*10\^9-1.5\*10\^9/L for grade 3 and/or \<1.0\*10\^9/L for grade 4, Lymphocytes (Absolute) as 0.350\*109-0.499\*10\^9 /L for grade 3 and/or \< 0.350\*10\^9 /L for grade 4, Alanine aminotransferase as 5.1-10.0\*ULN for grade 3 and/or \> 10.0\*ULN for grade 4, Aspartate aminotransferase as 5.1-10.0\*ULN for grade 3 and/or \> 10.0\*ULN for grade 4, Alkaline phosphatase as 5.1-10.0\*ULN for grade 3 and/or \> 10.0\*ULN for grade 4, Bilirubin (Total) as 2.6-5.0\*ULN for grade 3 and/or \> 5.0\*ULN for grade 4, Albumin as \< 20 g/L, Lipase (Total) as 3.1-5.0\*ULN for grade 3 and/or \> 5.0\*ULN for grade 4, and Creatinine as 1.9-3.4\*ULN for grade 3 and/or ≥ 3.5\*ULN for grade 4. |
| Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | From start of study treatment up to 7 days post last dose of study treatment (approximately 13 weeks) | AE was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not 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. |
| Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Week 1, 2, 4, 6, 8, 12, End of treatment, Follow-up Week 4, 8, and 24 | Participants who responded to treatment were assessed using proportion of subjects with hepatitis C Virus RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at each visit. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 5 centers in the United States.
Pre-assignment details
A total of 116 participants were enrolled, of which 113 received study treatment (60 cirrhotic cohort, 53: post-liver transplant cohort). Remaining 3 participants no longer met study criteria. Of the 60 participants in the cirrhotic cohort, 57 did not receive a treatment extension and 3 received a treatment extension after liver transplant.
Participants by arm
| Arm | Count |
|---|---|
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin Participants with liver transplant, received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. | 53 |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin Participants received 12 weeks of daclatasvir 60-mg and sofosbuvir 400-mg once daily (QD) orally, with ribavirin at a recommended initial dose of 600 mg and were followed for 24 weeks post-treatment. The dose of ribavirin could be titrated to 1000 mg/day if tolerated. | 60 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up Period | Death | 0 | 1 |
| Follow-up Period | Virologic Relapse | 3 | 10 |
| Treatment Period | Adverse Event | 1 | 0 |
| Treatment Period | Liver transplant, No extension needed | 0 | 1 |
| Treatment Period | Liver transplant, Treatment extension | 0 | 3 |
Baseline characteristics
| Characteristic | Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Total |
|---|---|---|---|
| Age, Continuous | 59.6 years STANDARD_DEVIATION 8.25 | 57.9 years STANDARD_DEVIATION 9.45 | 58.7 years STANDARD_DEVIATION 8.91 |
| Age, Customized <65 years | 42 participants | 50 participants | 92 participants |
| Age, Customized >=65 years | 11 participants | 10 participants | 21 participants |
| Gender Female | 15 Participants | 22 Participants | 37 Participants |
| Gender Male | 38 Participants | 38 Participants | 76 Participants |
| HCV genotype subtype Hepatitis C Virus genotype 1a | 31 participants | 34 participants | 65 participants |
| HCV genotype subtype Hepatitis C Virus genotype 1b | 10 participants | 11 participants | 21 participants |
| HCV genotype subtype Hepatitis C Virus genotype 2 | 0 participants | 5 participants | 5 participants |
| HCV genotype subtype Hepatitis C Virus genotype 3 | 11 participants | 6 participants | 17 participants |
| HCV genotype subtype Hepatitis C Virus genotype 4 | 0 participants | 4 participants | 4 participants |
| HCV genotype subtype Hepatitis C Virus genotype 5 | 0 participants | 0 participants | 0 participants |
| HCV genotype subtype Hepatitis C Virus genotype 6 | 1 participants | 0 participants | 1 participants |
| Hepatitis C Virus RNA | 6.61 log10 IU/mL STANDARD_DEVIATION 0.711 | 6.01 log10 IU/mL STANDARD_DEVIATION 0.617 | 6.29 log10 IU/mL STANDARD_DEVIATION 0.724 |
| Hepatitis C Virus RNA distribution <800,000 IU/mL | 6 participants | 27 participants | 33 participants |
| Hepatitis C Virus RNA distribution ≥800,000 IU/mL | 47 participants | 33 participants | 80 participants |
| IL-28B rs1297860 Genotype CC | 13 participants | 13 participants | 26 participants |
| IL-28B rs1297860 Genotype CT | 31 participants | 33 participants | 64 participants |
| IL-28B rs1297860 Genotype TT | 9 participants | 14 participants | 23 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 53 | 42 / 60 |
| serious Total, serious adverse events | 5 / 53 | 10 / 60 |
Outcome results
Primary
Percentage of Genotype-1 Infected Cirrhotic Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12)
SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
Time frame: Post-treatment follow-up Week 12
Population: All genotype 1 cirrhotic participants who received at least 1 dose of study therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Genotype-1 Infected Cirrhotic Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) | 82.2 Percentage of participants |
Primary
Percentage of HCV Genotype-1 Infected Post-liver Transplanted Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12)
SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation (\<LLOQ) i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
Time frame: Post-treatment follow-up Week 12
Population: All HCV genotype 1 infected post-transplant participants who received at least 1 dose of study therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of HCV Genotype-1 Infected Post-liver Transplanted Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) | 95.1 Percentage of participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death
AE was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not 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.
Time frame: From start of study treatment up to 7 days post last dose of study treatment (approximately 13 weeks)
Population: All treated participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | SAEs | 5 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | AEs leading to discontinuation | 6 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | AEs leading to interruption | 1 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | Treatment-related AEs | 35 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | Treatment-related SAEs | 0 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | Adverse events Grade 3 to 4 | 5 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | Serious adverse events Grade 3 to 4 | 2 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | Death | 0 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | Death | 0 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | SAEs | 10 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | Treatment-related SAEs | 0 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | AEs leading to discontinuation | 10 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | Serious adverse events Grade 3 to 4 | 8 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | AEs leading to interruption | 3 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | Adverse events Grade 3 to 4 | 11 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death | Treatment-related AEs | 37 participants |
Secondary
Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities
Grade 3-4 laboratory abnormalities were defined as: Hemoglobin as 6.50-7.4 g/dL for grade 3 and/or \< 6.5 g/dL for grade 4, Platelet count as 25\*10\^9-50\*10\^9 /L for grade 3 and/or \< 25.000\*10\^9 /L for grade 4, International normalized ratio as 2.1-3.0\*upper limit of normal (ULN) \> 3.0\*ULN for grade 3 and/or \> 3.0\*ULN for grade 4, Leukocytes as 1.0\*10\^9-1.5\*10\^9/L for grade 3 and/or \<1.0\*10\^9/L for grade 4, Lymphocytes (Absolute) as 0.350\*109-0.499\*10\^9 /L for grade 3 and/or \< 0.350\*10\^9 /L for grade 4, Alanine aminotransferase as 5.1-10.0\*ULN for grade 3 and/or \> 10.0\*ULN for grade 4, Aspartate aminotransferase as 5.1-10.0\*ULN for grade 3 and/or \> 10.0\*ULN for grade 4, Alkaline phosphatase as 5.1-10.0\*ULN for grade 3 and/or \> 10.0\*ULN for grade 4, Bilirubin (Total) as 2.6-5.0\*ULN for grade 3 and/or \> 5.0\*ULN for grade 4, Albumin as \< 20 g/L, Lipase (Total) as 3.1-5.0\*ULN for grade 3 and/or \> 5.0\*ULN for grade 4, and Creatinine as 1.9-3.4\*ULN for grade 3 and/or ≥ 3.5\*ULN for grade 4.
Time frame: From start of study treatment up to 7 days post last dose of study treatment
Population: All treated participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Platelet count | 0 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Hemoglobin | 2 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | International normalized ratio | 0 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Leukocytes | 2 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Lymphocytes (Absolute) | 3 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Alanine aminotransferase | 0 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Aspartate aminotransferase | 0 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Alkaline phosphatase | 1 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Bilirubin (Total) | 2 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Albumin | 0 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Lipase (Total) | 2 participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Creatinine | 2 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Lipase (Total) | 3 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Aspartate aminotransferase | 3 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Hemoglobin | 5 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Platelet count | 4 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Albumin | 1 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | International normalized ratio | 1 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Alkaline phosphatase | 0 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Leukocytes | 0 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Creatinine | 2 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Lymphocytes (Absolute) | 6 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Bilirubin (Total) | 9 participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities | Alanine aminotransferase | 2 participants |
Secondary
Percentage of Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6
SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
Time frame: Post-treatment follow-up Week 12
Population: All treated participants who took at least 1 dose of study medication. Here, 'n' signifies participants evaluable for SVR12 at the specified time point in each group, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6 | All Genotypes (n =53, 60) | 94.3 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6 | HCV Genotype 4 (n =0, 4) | NA Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6 | HCV Genotype 2 (n =0, 5) | NA Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6 | HCV Genotype 6 (n =1, 0) | 100 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6 | HCV Genotype 3 (n =11, 6) | 90.9 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6 | HCV Genotype 6 (n =1, 0) | NA Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6 | HCV Genotype 2 (n =0, 5) | 80 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6 | HCV Genotype 3 (n =11, 6) | 83.3 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6 | HCV Genotype 4 (n =0, 4) | 100 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6 | All Genotypes (n =53, 60) | 83.3 Percentage of participants |
Secondary
Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24
Participants who responded to treatment were assessed using proportion of subjects with hepatitis C Virus RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at each visit.
Time frame: Week 1, 2, 4, 6, 8, 12, End of treatment, Follow-up Week 4, 8, and 24
Population: All treated participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Week 1 | 22.6 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Week 2 | 67.9 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Week 4 | 94.3 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Week 6 | 96.2 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Week 8 | 98.1 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Week 12 | 98.1 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | End of treatment | 100.0 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Follow-up Week 4 (SVR4) | 98.1 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Follow-up Week 8 (SVR8) | 96.2 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Follow-up Week 24 (SVR24) | 94.3 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Follow-up Week 4 (SVR4) | 88.3 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Week 1 | 15.0 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Week 12 | 93.3 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Week 2 | 45.0 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Follow-up Week 24 (SVR24) | 80.0 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Week 4 | 95.0 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | End of treatment | 96.7 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Week 6 | 91.7 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Follow-up Week 8 (SVR8) | 86.7 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 | Week 8 | 95.0 Percentage of participants |
Secondary
Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment
Participants who responded to treatment were assessed using proportion of subjects with hepatitis C Virus RNA levels below the lower limit of quantitation i.e., 25 IU/mL target not detected, at each on-treatment visit.
Time frame: Week 1, 2, 4, 6, 8, 12, End of treatment
Population: All treated participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment | Week 4 | 56.6 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment | Week 8 | 98.1 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment | Week 2 | 13.2 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment | Week 12 | 98.1 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment | Week 6 | 84.9 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment | End of treatment | 100.0 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment | Week 1 | 3.8 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment | End of treatment | 96.7 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment | Week 1 | 1.7 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment | Week 2 | 11.7 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment | Week 4 | 53.3 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment | Week 6 | 76.7 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment | Week 8 | 93.3 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment | Week 12 | 93.3 Percentage of participants |
Secondary
Percentage of Participants With CC or Non-CC Genotype Who Achieved Sustained Virologic Response at 12 Weeks After the Last Dose of Study Drug (SVR12)
Participants categorized into 2 genotypes (CC and non-CC) based on single nucleotide polymorphism in the IL28B gene were assessed for SVR12, defined as response in which hepatitis C virus RNA levels be \<lower limit of quantitation ie, 25 IU/mL or below 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. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
Time frame: Post-treatment follow-up Week 12
Population: All treated participants. Here, 'n' signifies participants evaluable for SVR12 at the specified time point in each group, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants With CC or Non-CC Genotype Who Achieved Sustained Virologic Response at 12 Weeks After the Last Dose of Study Drug (SVR12) | CC type (n = 13, 13) | 100 Percentage of participants |
| Post-liver Transplant Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants With CC or Non-CC Genotype Who Achieved Sustained Virologic Response at 12 Weeks After the Last Dose of Study Drug (SVR12) | Non-CC type (n = 40, 47) | 92.5 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants With CC or Non-CC Genotype Who Achieved Sustained Virologic Response at 12 Weeks After the Last Dose of Study Drug (SVR12) | CC type (n = 13, 13) | 84.6 Percentage of participants |
| Cirrhotic Cohort: Daclatasvir+Sofosbuvir+Ribavirin | Percentage of Participants With CC or Non-CC Genotype Who Achieved Sustained Virologic Response at 12 Weeks After the Last Dose of Study Drug (SVR12) | Non-CC type (n = 40, 47) | 78.7 Percentage of participants |