Hepatitis C Virus Infection
Conditions
Keywords
HCV genotype 1, HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, GS-7977, GS-5885, Ribavirin, Sofosbuvir, ledipasvir, Hepatitis C, Hepatitis C, Chronic, Liver Diseases, Virus Diseases, Antiviral Agents, HCV/HIV co-infection
Brief summary
The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed dose combination (FDC) with or without ribavirin (RBV) in adults with chronic hepatitis C virus (HCV) infection.
Interventions
DRUGLDV/SOF
90/400 mg FDC tablet administered orally once daily
DRUGRBV
Tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (\< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
Sponsors
Gilead Sciences
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
Key Inclusion Criteria: * Participants who failed treatment in Study GS-US-334-0119 who meet relevant inclusion/
Exclusion criteria
are eligible for retreatment in this study * Chronic genotype 1 HCV infection * HCV treatment-naive * HCV RNA \> 10,000 IU/mL at screening * Absence of cirrhosis * Screening laboratory values within defined thresholds * Use of two effective contraception methods if female of childbearing potential or sexually active male Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | Posttreatment Week 12 | SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug. |
| Percentage of Participants Who Discontinued Study Drug Due to Any Adverse Event (AE) | Up to 12 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response (SVR) at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | Posttreatment Weeks 4 and 24 | SVR4 and SVR24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks following the last dose of study drug, respectively. |
| Percentage of Participants With HCV RNA < LLOQ on Treatment | Up to 12 weeks | — |
| HCV RNA Change From Day 1 | Up to 12 weeks | — |
| Percentage of Participants With Virologic Failure | Up to Posttreatment Week 24 | Virologic failure was defined as * On-treatment virologic failure * confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ, while on treatment (ie, breakthrough), * confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment (ie, rebound), HCV RNA persistently ≥ LLOQ through 8 weeks of treatment (ie, nonresponse) * Relapse * HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement |
| Percentage of HIV/HCV- Coinfected Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4 | Up to Posttreatment Week 4 | — |
| For HIV/HCV- Coinfected Participants, Change From Baseline in CD4 T-cell Count at the End of Treatment and Posttreatment Week 4 | Up to Posttreatment Week 4 | — |
Countries
Estonia, Russia
Participant flow
Recruitment details
Participants were enrolled at study sites in Russia and Estonia. The first participant was screened on 17 June 2015. The last study visit occurred on 30 June 2016.
Pre-assignment details
169 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) LDV/SOF(90/400 mg) FDC tablet once daily for 8 weeks in treatment-naive (TN) participants with genotype 1 HCV infection without cirrhosis | 67 |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) LDV/SOF (90/400 mg) FDC tablet once daily for 8 weeks in treatment naive participants with genotype 1 HCV infection without cirrhosis and coinfected with HIV-1 | 59 |
| LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) LDV/SOF (90/400 mg) FDC tablet once daily + weight-based ribavirin (RBV) (1000-1200 mg in a divided daily dose) for 12 weeks in treatment-experienced (TE) participants with genotype 1 or 3 HCV infection who failed to achieve SVR in a previous Gilead sofosbuvir study | 27 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) | Total | LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | LDV/SOF 8 Weeks (TN, HCV-monoinfected) |
|---|---|---|---|---|
| Age, Continuous | 47 years STANDARD_DEVIATION 11.2 | 40 years STANDARD_DEVIATION 11.1 | 34 years STANDARD_DEVIATION 5.5 | 42 years STANDARD_DEVIATION 12.6 |
| Cirrhosis Status No | 17 Participants | 143 Participants | 59 Participants | 67 Participants |
| Cirrhosis Status Yes | 10 Participants | 10 Participants | 0 Participants | 0 Participants |
| HCV RNA | 6.3 log10 IU/mL STANDARD_DEVIATION 0.67 | 6.0 log10 IU/mL STANDARD_DEVIATION 0.66 | 6.1 log10 IU/mL STANDARD_DEVIATION 0.54 | 5.9 log10 IU/mL STANDARD_DEVIATION 0.72 |
| HCV RNA Category < 800,000 IU/mL | 8 Participants | 60 Participants | 23 Participants | 29 Participants |
| HCV RNA Category ≥ 800,000 IU/mL | 19 Participants | 93 Participants | 36 Participants | 38 Participants |
| IL28b Status CC | 7 Participants | 33 Participants | 9 Participants | 17 Participants |
| IL28b Status CT | 18 Participants | 100 Participants | 41 Participants | 41 Participants |
| IL28b Status TT | 2 Participants | 20 Participants | 9 Participants | 9 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 27 Participants | 153 Participants | 59 Participants | 67 Participants |
| Race/Ethnicity, Customized White | 27 Participants | 152 Participants | 59 Participants | 66 Participants |
| Region of Enrollment Estonia | 0 Participants | 18 Participants | 12 Participants | 6 Participants |
| Region of Enrollment Russian Federation | 27 Participants | 135 Participants | 47 Participants | 61 Participants |
| Sex: Female, Male Female | 9 Participants | 67 Participants | 25 Participants | 33 Participants |
| Sex: Female, Male Male | 18 Participants | 86 Participants | 34 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 67 | 0 / 59 | 0 / 27 |
| other Total, other adverse events | 5 / 67 | 2 / 59 | 8 / 27 |
| serious Total, serious adverse events | 0 / 67 | 0 / 59 | 0 / 27 |
Outcome results
Primary
Percentage of Participants Who Discontinued Study Drug Due to Any Adverse Event (AE)
Time frame: Up to 12 weeks
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | Percentage of Participants Who Discontinued Study Drug Due to Any Adverse Event (AE) | 0 percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | Percentage of Participants Who Discontinued Study Drug Due to Any Adverse Event (AE) | 0 percentage of participants |
| LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) | Percentage of Participants Who Discontinued Study Drug Due to Any Adverse Event (AE) | 0 percentage of participants |
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
Time frame: Posttreatment Week 12
Population: Full Analysis Set (FAS) included participants who were enrolled into the study and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | 96.6 percentage of participants |
| LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) | Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | 96.3 percentage of participants |
Secondary
For HIV/HCV- Coinfected Participants, Change From Baseline in CD4 T-cell Count at the End of Treatment and Posttreatment Week 4
Time frame: Up to Posttreatment Week 4
Population: Participant in the Safety analysis set (with or without prior antiretroviral (ARV) treatment) with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | For HIV/HCV- Coinfected Participants, Change From Baseline in CD4 T-cell Count at the End of Treatment and Posttreatment Week 4 | Change at Week 4 | 47 cells/µL | Standard Deviation 120.5 |
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | For HIV/HCV- Coinfected Participants, Change From Baseline in CD4 T-cell Count at the End of Treatment and Posttreatment Week 4 | Change at Week 8 | 45 cells/µL | Standard Deviation 122.7 |
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | For HIV/HCV- Coinfected Participants, Change From Baseline in CD4 T-cell Count at the End of Treatment and Posttreatment Week 4 | Change at Posttreatment Week 4 | 74 cells/µL | Standard Deviation 117.8 |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | For HIV/HCV- Coinfected Participants, Change From Baseline in CD4 T-cell Count at the End of Treatment and Posttreatment Week 4 | Change at Week 4 | 159 cells/µL | Standard Deviation 114.9 |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | For HIV/HCV- Coinfected Participants, Change From Baseline in CD4 T-cell Count at the End of Treatment and Posttreatment Week 4 | Change at Week 8 | 202 cells/µL | Standard Deviation 178.1 |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | For HIV/HCV- Coinfected Participants, Change From Baseline in CD4 T-cell Count at the End of Treatment and Posttreatment Week 4 | Change at Posttreatment Week 4 | 172 cells/µL | Standard Deviation 114.1 |
Secondary
HCV RNA Change From Day 1
Time frame: Up to 12 weeks
Population: Participants in Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | HCV RNA Change From Day 1 | Week 2 | -4.50 log10 IU/mL | Standard Deviation 0.687 |
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | HCV RNA Change From Day 1 | Week 1 | -3.97 log10 IU/mL | Standard Deviation 0.675 |
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | HCV RNA Change From Day 1 | Week 4 | -4.74 log10 IU/mL | Standard Deviation 0.723 |
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | HCV RNA Change From Day 1 | Week 12 | NA log10 IU/mL | — |
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | HCV RNA Change From Day 1 | Week 8 | -4.74 log10 IU/mL | Standard Deviation 0.723 |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | HCV RNA Change From Day 1 | Week 12 | NA log10 IU/mL | — |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | HCV RNA Change From Day 1 | Week 1 | -4.34 log10 IU/mL | Standard Deviation 0.626 |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | HCV RNA Change From Day 1 | Week 2 | -4.76 log10 IU/mL | Standard Deviation 0.522 |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | HCV RNA Change From Day 1 | Week 4 | -4.89 log10 IU/mL | Standard Deviation 0.534 |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | HCV RNA Change From Day 1 | Week 8 | -4.91 log10 IU/mL | Standard Deviation 0.536 |
| LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) | HCV RNA Change From Day 1 | Week 4 | -5.08 log10 IU/mL | Standard Deviation 0.642 |
| LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) | HCV RNA Change From Day 1 | Week 1 | -4.12 log10 IU/mL | Standard Deviation 0.582 |
| LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) | HCV RNA Change From Day 1 | Week 12 | -5.11 log10 IU/mL | Standard Deviation 0.671 |
| LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) | HCV RNA Change From Day 1 | Week 2 | -4.83 log10 IU/mL | Standard Deviation 0.63 |
| LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) | HCV RNA Change From Day 1 | Week 8 | -5.11 log10 IU/mL | Standard Deviation 0.671 |
Secondary
Percentage of HIV/HCV- Coinfected Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4
Time frame: Up to Posttreatment Week 4
Population: Participants in the Safety Analysis Set (who had HIV RNA \< 50 Copies/mL at baseline) with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | Percentage of HIV/HCV- Coinfected Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4 | Week 4 | 100.0 percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | Percentage of HIV/HCV- Coinfected Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4 | Week 8 | 100.0 percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | Percentage of HIV/HCV- Coinfected Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4 | Posttreatment Week 4 | 97.2 percentage of participants |
Secondary
Percentage of Participants With HCV RNA < LLOQ on Treatment
Time frame: Up to 12 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 1 | 20.9 percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 100.0 percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 65.7 percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 100.0 percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 12 | NA percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 12 | NA percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 1 | 39.0 percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 98.3 percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 96.6 percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 69.5 percentage of participants |
| LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 12 | 100.0 percentage of participants |
| LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 59.3 percentage of participants |
| LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 88.9 percentage of participants |
| LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 100.0 percentage of participants |
| LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 1 | 3.7 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response (SVR) at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4 and SVR24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Time frame: Posttreatment Weeks 4 and 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | Percentage of Participants With Sustained Virologic Response (SVR) at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 100.0 percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | Percentage of Participants With Sustained Virologic Response (SVR) at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 100.0 percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | Percentage of Participants With Sustained Virologic Response (SVR) at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 96.6 percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | Percentage of Participants With Sustained Virologic Response (SVR) at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 96.6 percentage of participants |
| LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) | Percentage of Participants With Sustained Virologic Response (SVR) at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 96.3 percentage of participants |
| LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) | Percentage of Participants With Sustained Virologic Response (SVR) at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 96.3 percentage of participants |
Secondary
Percentage of Participants With Virologic Failure
Virologic failure was defined as * On-treatment virologic failure * confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ, while on treatment (ie, breakthrough), * confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment (ie, rebound), HCV RNA persistently ≥ LLOQ through 8 weeks of treatment (ie, nonresponse) * Relapse * HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement
Time frame: Up to Posttreatment Week 24
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF 8 Weeks (TN, HCV-monoinfected) | Percentage of Participants With Virologic Failure | 0 percentage of participants |
| LDV/SOF 8 Weeks (TN, HCV/HIV-coinfected) | Percentage of Participants With Virologic Failure | 3.4 percentage of participants |
| LDV/SOF + RBV 12 Weeks (TE, SOF-treated, HCV-monoinfected) | Percentage of Participants With Virologic Failure | 3.7 percentage of participants |