Phase 2
N=38
Sofosbuvir Plus Ribavirin, or Ledipasvir/Sofosbuvir in Adults With HCV Infection and Renal Insufficiency
HCV Infection
Bottom Line
View on ClinicalTrials.gov: NCT01958281 ↗Enrolled (actual)
38
Serious AEs
21.1%
Results posted
Aug 2018
Primary outcome: Primary: Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) — 40.0; 60.0; 100.0 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- SOF (Drug); RBV (Drug); LDV/SOF (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Gilead Sciences
- Primary completion
- Jul 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) |
40.0; 60.0; 100.0 | — |
| PRIMARY Percentage of Participants Experiencing Treatment-Emergent Adverse Events |
100.0; 90.0; 72.2 | — |
| PRIMARY Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities |
100.0; 100.0; 100.0 | — |
| PRIMARY Percentage of Participants Experiencing Clinically Significant 12-lead Electrocardiogram (ECG) Abnormalities |
0; 0; 5.6 | — |
| PRIMARY Percentage of Participants Experiencing Treatment-Emergent Adverse Events Associated With Vital Sign Abnormalities |
10.0; 0; 0 | — |
| PRIMARY Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) |
1093.9; 1630.5; 2120.2; 4026.2; 31859.4; 51989.6 | — |
| PRIMARY PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) |
1302.7; 1571.3; 2223.2; 3213.9; 31078.3; 46810.1 | — |
| PRIMARY PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) |
3536.8; 7716.6; 71463.3; 18460.1 | — |
| PRIMARY PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) |
575.9; 976.8; 308.3; 538.3; 1750.0; 2721.4 | — |
| PRIMARY PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) |
903.9; 1422.9; 352.2; 509.1; 1727.0; 2645.0 | — |
| PRIMARY PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) |
2018.1; 1021.6; 3570.0; 903.4 | — |
| PRIMARY PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) |
NA; NA; 3.7; 20.8; 1023.0; 1736.1 | — |
| PRIMARY PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) |
NA; NA; 2.3; 10.4; 952.5; 1356.0 | — |
| PRIMARY PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) |
2.9; 59.3; 2568.2; 705.0 | — |
| SECONDARY Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) |
40.0; 60.0; 100.0 | — |
| SECONDARY Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) |
40.0; 60.0; 100.0 | — |
| SECONDARY Percentage of Participants With Overall Virologic Failure |
50.0; 40.0; 0 | — |
| SECONDARY PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) |
885.0; 1607.7; 1973.3; 3965.7; 31859.4; 51989.6 | — |
| SECONDARY PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) |
1177.7; 1548.1; 1867.1; 3133.0; 31078.3; 46810.1 | — |
| SECONDARY PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) |
3519.3; 7657.6; 69177.7; 18044.3 | — |
| SECONDARY PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) |
68.0; 21.3; 37.6; 35.8; 1023.0; 1736.1 | — |
| SECONDARY PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) |
100.7; 22.7; 72.2; 32.1; 952.5; 1412.9 | — |
| SECONDARY PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) |
56.3; 70.5; 2570.6; 700.6 | — |
| SECONDARY PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) |
1.00; 1.50; 2.17; 4.00; 4.00; 6.00 | — |
| SECONDARY PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) |
1.04; 0.50; 2.17; 2.00; 5.11; 5.00 | — |
| SECONDARY PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) |
1.00; 2.00; 4.02; 6.00 | — |
| SECONDARY PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) |
4.00; 6.00; 12.00; 24.00; 24.00; 24.00 | — |
| SECONDARY PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) |
4.00; 4.03; 12.00; 24.00; 24.00; 24.00 | — |
| SECONDARY PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) |
12.00; 24.00; 24.00; 24.00 | — |
| SECONDARY PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) |
1.0419; 1.0155; 0.2078; 0.1771; 0.0275; 0.0273 | — |
| SECONDARY PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) |
1.4002; 1.2154; 0.2232; 0.1818; 0.0332; 0.0313 | — |
| SECONDARY PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) |
0.6033; 0.1705; 0.0214; 0.0305 | — |
| SECONDARY PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) |
0.67; 0.67; 3.31; 3.88; 30.53; 29.05 | — |
| SECONDARY PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) |
0.48; 0.57; 3.03; 3.88; 22.03; 33.54 | — |
| SECONDARY PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) |
1.18; 4.02; 39.30; 25.96 | — |
Summary
The primary objectives of this study are to evaluate the safety and efficacy of sofosbuvir (SOF) plus ribavirin (RBV) for 24 weeks and ledipasvir/sofosbuvir (LDV/SOF) for 12 weeks, and to evaluate the steady state pharmacokinetics (PK) of SOF and its metabolites and LDV in participants with genotype (GT) 1, 3, or 4 hepatitis C virus (HCV) infection who have chronic renal insufficiency (impaired kidney function).
Eligibility Criteria
Key Inclusion Criteria
- Cohorts 1 and 2: chronic genotype 1 or 3 HCV infection
- Cohort 3: chronic genotype 1 or 4 HCV infection
- HCV RNA ≥ 10^4 IU/mL at screening
- Screening labs within defined thresholds
- Cirrhosis determination at screening
Key Exclusion Criteria
- Females who are pregnant or nursing or males who have a pregnant partner
- Prior null response to pegylated interferon (Peg-IFN)+RBV therapy (Cohorts 1 and 2) or for individuals with cirrhosis, prior treatment failure with IFN-based therapy not resulting from treatment intolerance (Cohort 3)
- Current of prior history of hepatic decompensation
- Infection with hepatitis B virus (HBV) or HIV
- History of clinically significant illness (including psychiatric or cardiac) or any other medical disorder that may interfere with individual's treatment and/or adherence to the protocol
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT01958281). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.