Hepatitis C
Conditions
Brief summary
The purpose of this study is to determine whether 24 weeks of Daclatasvir and Sofosbuvir with Ribavirin is safe and effective in the treatment of genotype 3 hepatitis C infected patients with liver cirrhosis.
Interventions
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding Bristol-Myers Squibb (BMS) Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Genotype 3 HCV * HCV RNA ≥10000 IU (International Unit)/mL * Compensated Liver Cirrhosis * BMI 18-40 kg/m2 * Previously treated for HCV or never treated for HCV
Exclusion criteria
* Infection with HCV other than Genotype 3. Mixed infection of any genotype * Evidence of decompensated liver disease * Previous exposure to NS5A inhibitors Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response (SVR12) | Week 12 | SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA measurements are excluded after the start of non-study anti-HCV medication on treatment or during follow-up. Modified (mITT) approach is based on treated subjects. The numerator is based on subjects meeting the response criteria and the Next Value Carried Backwards approach. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve SVR12 in the Presence and Absence of Baseline NS5A (Non-structural Protein 5A) Resistance-associated Polymorphisms | Week 12 (Follow-up period) | SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA measurements are excluded after the start of non-study anti-HCV medication on treatment or during follow-up. Modified (mITT) approach is based on treated subjects. The numerator is based on subjects meeting the response criteria and the Next Value Carried Backwards approach. |
| Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | At Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, End of Treatment (24 weeks), Follow Up Week 4 (28 weeks), Follow Up Week 12 (36 weeks), Follow Up Week 24 (48 weeks) | HCV RNA measurements are excluded after the start of non-study anti-HCV medication on treatment or during follow-up. Modified (mITT) approach is based on treated subjects. The numerator is based on subjects meeting the response criteria. SVR12 is based on Next Value Carried Backwards approach. |
| Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | At Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, End of Treatment, Follow Up Week 4, Follow Up Week 12, Follow Up Week 24 | HCV RNA measurements are excluded after the start of non-study anti-HCV medication on treatment or during follow-up. Modified (mITT) approach is based on treated subjects. The numerator is based on subjects meeting the response criteria. |
Countries
Canada, United States
Participant flow
Pre-assignment details
Of the 106 subjects enrolled, 78 participants entered the treatment period and received study treatment; 28 participants were enrolled but did not enter the treatment period. 26 were due to no longer meeting study criteria; 1 was due to poor/non-compliance (missed Day 1 visit); and 1 was other (missed screening window).
Participants by arm
| Arm | Count |
|---|---|
| Treatment Naive HCV treatment-naive: No previous exposure to any interferon (IFN) formulation (ie, IFN or peg-IFN), RBV, or any HCV DAAs | 54 |
| Treatment Experienced HCV treatment-experienced: Previous treatment with IFN/RBV, SOF + RBV, and other anti-HCV agents | 24 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow Up Period | Unable to return for follow-up | 0 | 1 |
| Follow Up Period | Unable to return for week 24 follow-up | 0 | 1 |
| Treatment Period | Adverse Event | 0 | 1 |
| Treatment Period | Lost to Follow-up | 3 | 0 |
| Treatment Period | Participant moved to another province | 1 | 0 |
| Treatment Period | Participant request to discontinue | 1 | 1 |
| Treatment Period | Participant was incarcerated | 0 | 1 |
Baseline characteristics
| Characteristic | Treatment Experienced | Total | Treatment Naive |
|---|---|---|---|
| Age, Continuous | 55.3 Years STANDARD_DEVIATION 4.9 | 54.4 Years STANDARD_DEVIATION 7.16 | 54 Years STANDARD_DEVIATION 7.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 13 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 28 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 37 Participants | 27 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 69 Participants | 48 Participants |
| Sex: Female, Male Female | 7 Participants | 21 Participants | 14 Participants |
| Sex: Female, Male Male | 17 Participants | 57 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 78 | 0 / 54 | 0 / 24 |
| other Total, other adverse events | 63 / 78 | 44 / 54 | 19 / 24 |
| serious Total, serious adverse events | 8 / 78 | 4 / 54 | 4 / 24 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response (SVR12)
SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA measurements are excluded after the start of non-study anti-HCV medication on treatment or during follow-up. Modified (mITT) approach is based on treated subjects. The numerator is based on subjects meeting the response criteria and the Next Value Carried Backwards approach.
Time frame: Week 12
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HCV Treatment Naive | Percentage of Participants With Sustained Virologic Response (SVR12) | 92.6 Percentage of participants |
| HCV Treatment Experienced | Percentage of Participants With Sustained Virologic Response (SVR12) | 75.0 Percentage of participants |
Secondary
Percentage of Participants Who Achieve SVR12 in the Presence and Absence of Baseline NS5A (Non-structural Protein 5A) Resistance-associated Polymorphisms
SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA measurements are excluded after the start of non-study anti-HCV medication on treatment or during follow-up. Modified (mITT) approach is based on treated subjects. The numerator is based on subjects meeting the response criteria and the Next Value Carried Backwards approach.
Time frame: Week 12 (Follow-up period)
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HCV Treatment Naive | Percentage of Participants Who Achieve SVR12 in the Presence and Absence of Baseline NS5A (Non-structural Protein 5A) Resistance-associated Polymorphisms | NS5A-Y93 Polymorphism: YES | 85.7 Percentage of participants |
| HCV Treatment Naive | Percentage of Participants Who Achieve SVR12 in the Presence and Absence of Baseline NS5A (Non-structural Protein 5A) Resistance-associated Polymorphisms | NS5A-Y93 Polymorphism: NO | 93.6 Percentage of participants |
| HCV Treatment Experienced | Percentage of Participants Who Achieve SVR12 in the Presence and Absence of Baseline NS5A (Non-structural Protein 5A) Resistance-associated Polymorphisms | NS5A-Y93 Polymorphism: YES | 0.0 Percentage of participants |
| HCV Treatment Experienced | Percentage of Participants Who Achieve SVR12 in the Presence and Absence of Baseline NS5A (Non-structural Protein 5A) Resistance-associated Polymorphisms | NS5A-Y93 Polymorphism: NO | 78.3 Percentage of participants |
Secondary
Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24
HCV RNA measurements are excluded after the start of non-study anti-HCV medication on treatment or during follow-up. Modified (mITT) approach is based on treated subjects. The numerator is based on subjects meeting the response criteria. SVR12 is based on Next Value Carried Backwards approach.
Time frame: At Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, End of Treatment (24 weeks), Follow Up Week 4 (28 weeks), Follow Up Week 12 (36 weeks), Follow Up Week 24 (48 weeks)
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Week 16 | 90.7 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Week 4 | 92.6 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Week 20 | 94.4 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Follow Up Week 24 | 92.6 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Week 24 | 88.9 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Week 8 | 98.1 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | End of Treatment | 100.0 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Week 2 | 50.0 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Follow Up Week 4 | 88.9 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Follow Up Week 12 (Imputed) | 92.6 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Week 12 | 92.6 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Week 1 | 14.8 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Follow Up Week 24 | 66.7 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Week 1 | 12.5 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Week 2 | 54.2 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Week 4 | 75.0 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Week 8 | 91.7 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Week 12 | 87.5 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Week 16 | 83.3 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Week 20 | 83.3 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Week 24 | 87.5 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | End of Treatment | 91.7 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Follow Up Week 12 (Imputed) | 75.0 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TD or TND Through Follow up Week 24 | Follow Up Week 4 | 79.2 Percentage |
Secondary
Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24
HCV RNA measurements are excluded after the start of non-study anti-HCV medication on treatment or during follow-up. Modified (mITT) approach is based on treated subjects. The numerator is based on subjects meeting the response criteria.
Time frame: At Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, End of Treatment, Follow Up Week 4, Follow Up Week 12, Follow Up Week 24
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Week 16 | 90.7 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Week 20 | 94.4 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Week 1 | 1.9 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Week 2 | 11.1 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Week 4 | 64.8 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Week 8 | 94.4 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Week 12 | 90.7 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Week 24 | 88.9 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | End of Treatment | 100.0 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Follow Up Week 4 | 88.9 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Follow Up Week 12 | 90.7 Percentage |
| HCV Treatment Naive | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Follow Up Week 24 | 90.7 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Follow Up Week 12 | 75.0 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Week 16 | 79.2 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Week 12 | 83.3 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Week 20 | 83.3 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Follow Up Week 4 | 79.2 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Week 1 | 0.0 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Week 24 | 83.3 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Week 2 | 12.5 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Follow Up Week 24 | 66.7 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Week 4 | 62.5 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | End of Treatment | 87.5 Percentage |
| HCV Treatment Experienced | Percentage of Subjects Who Achieve HCV RNA < LLOQ, TND Through Follow up Week 24 | Week 8 | 83.3 Percentage |