HCV Infection
Conditions
Keywords
genotype 1
Brief summary
The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) with or without ribavirin (RBV) in participants with chronic genotype 1 hepatitis C virus (HCV) infection who have participated in a prior Gilead-sponsored HCV treatment study, and who did not achieve sustained virologic response (SVR24), defined as HCV RNA \< lower limit of quantification (LLOQ) 24 weeks after last dose of study drug (SVR24).
Interventions
DRUGLDV/SOF
Tablet(s) 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) Participants in the LDV/SOF+RBV 24 weeks group will dose adjust RBV according to hemoglobin and renal status as stated in the RBV package insert.
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: * Willing and able to provide written informed consent * Infection with HCV genotype 1 * HCV RNA \> LLOQ at screening * Participation in a prior Gilead-sponsored study * Screening laboratory values within defined thresholds * Use of two effective contraception methods if female of childbearing potential or sexually active male * Must be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator * Must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments Key
Exclusion criteria
* Pregnant or nursing female or male with pregnant female partner * Co-infection with HIV or hepatitis B virus (HBV) * Current or prior history of clinical hepatic decompensation (Groups 1 and 2 only) * Hepatocellular carcinoma (HCC) * History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | Post-treatment Week 12 | SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study treatment. |
| Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | Up to 24 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 treatment, respectively. |
| Percentage of Participants With HCV RNA < LLOQ While on Treatment | Baseline to Week 24 | — |
| Change in HCV RNA From Baseline | Baseline to Week 8 | — |
| Percentage of Participants With Virologic Failure | Up to posttreatment Week 24 | Virologic failure was defined as: * On-treatment virologic failure: * Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment), or * Rebound (confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or * Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) * Virologic relapse: * Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit confirmed with 2 consecutive values or last available posttreatment measurement |
Countries
Australia, France, Puerto Rico, Spain, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the US, Australia, and Spain. The first participant was screened on 30 July 2014. The last study visit occurred on 12 November 2015.
Pre-assignment details
101 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| LDV/SOF + RBV 12 Weeks (Group 1) Participants who failed a prior SOF+RBV ± Peg-IFN regimen received ledipasvir/sofosbuvir (LDV/SOF) (90/400 mg) fixed-dose combination (FDC) tablet administered orally once daily + ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for 12 weeks | 51 |
| LDV/SOF 24 Weeks (Group 2) Participants who failed a prior LDV/SOF±RBV regimen received LDV/SOF FDC (90/400 mg) tablet administered orally once daily for 24 weeks | 41 |
| LDV/SOF + RBV 24 Weeks (Group 3) Participants with advanced compensated or decompensated cirrhosis who failed a prior SOF+RBV regimen received LDV/SOF FDC (90/400 mg) tablet administered orally once daily + RBV (adjusted for hemoglobin and renal status) for 24 weeks | 8 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 12 | 0 |
Baseline characteristics
| Characteristic | LDV/SOF + RBV 24 Weeks (Group 3) | LDV/SOF + RBV 12 Weeks (Group 1) | LDV/SOF 24 Weeks (Group 2) | Total |
|---|---|---|---|---|
| Age, Continuous | 61 Years STANDARD_DEVIATION 6.7 | 54 Years STANDARD_DEVIATION 8.7 | 58 Years STANDARD_DEVIATION 6.9 | 57 Years STANDARD_DEVIATION 8.2 |
| HCV RNA | 5.6 log10 IU/mL STANDARD_DEVIATION 0.44 | 6.2 log10 IU/mL STANDARD_DEVIATION 0.58 | 6.2 log10 IU/mL STANDARD_DEVIATION 0.62 | 6.2 log10 IU/mL STANDARD_DEVIATION 0.61 |
| HCV RNA Category < 800,000 IU/mL | 6 Participants | 13 Participants | 11 Participants | 30 Participants |
| HCV RNA Category >= 800,000 IU/mL | 2 Participants | 38 Participants | 30 Participants | 70 Participants |
| IL28B CC | 0 Participants | 4 Participants | 3 Participants | 7 Participants |
| IL28B CT | 7 Participants | 33 Participants | 27 Participants | 67 Participants |
| IL28B TT | 1 Participants | 14 Participants | 11 Participants | 26 Participants |
| Prior HCV Treatment Experience LDV/SOF | 0 Particiapants | 0 Particiapants | 18 Particiapants | 18 Particiapants |
| Prior HCV Treatment Experience LDV/SOF+GS-9669 | 0 Particiapants | 0 Particiapants | 8 Particiapants | 8 Particiapants |
| Prior HCV Treatment Experience LDV/SOF+RBV | 0 Particiapants | 0 Particiapants | 15 Particiapants | 15 Particiapants |
| Prior HCV Treatment Experience SOF+PEG+RBV | 0 Particiapants | 25 Particiapants | 0 Particiapants | 25 Particiapants |
| Prior HCV Treatment Experience SOF+RBV | 8 Particiapants | 20 Particiapants | 0 Particiapants | 28 Particiapants |
| Prior HCV Treatment Experience Without SOF | 0 Particiapants | 6 Particiapants | 0 Particiapants | 6 Particiapants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 8 Participants | 10 Participants | 19 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 4 Participants | 5 Participants | 9 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 8 Participants | 47 Participants | 36 Participants | 91 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 43 Participants | 31 Participants | 81 Participants |
| Region of Enrollment Australia | 1 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment Spain | 3 participants | 0 participants | 0 participants | 3 participants |
| Region of Enrollment United States | 4 participants | 51 participants | 41 participants | 96 participants |
| Sex: Female, Male Female | 1 Participants | 20 Participants | 7 Participants | 28 Participants |
| Sex: Female, Male Male | 7 Participants | 31 Participants | 34 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 37 / 51 | 16 / 41 | 7 / 8 |
| serious Total, serious adverse events | 2 / 51 | 2 / 41 | 2 / 8 |
Outcome results
Primary
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Time frame: Up to 24 Weeks
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF + RBV 12 Weeks (Group 1) | Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | 5.9 Percentage of participants |
| LDV/SOF 24 Weeks (Group 2) | Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | 0 Percentage of participants |
| LDV/SOF + RBV 24 Weeks (Group 3) | Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | 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 treatment.
Time frame: Post-treatment Week 12
Population: Full Analysis Set: participants enrolled into the study and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF + RBV 12 Weeks (Group 1) | Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | 98.0 Percentage of participants |
| LDV/SOF 24 Weeks (Group 2) | Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | 70.7 Percentage of participants |
| LDV/SOF + RBV 24 Weeks (Group 3) | Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 Percentage of participants |
Secondary
Change in HCV RNA From Baseline
Time frame: Baseline to Week 8
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDV/SOF + RBV 12 Weeks (Group 1) | Change in HCV RNA From Baseline | Week 4 | -5.07 log10 IU/mL | Standard Deviation 0.565 |
| LDV/SOF + RBV 12 Weeks (Group 1) | Change in HCV RNA From Baseline | Week 1 | -4.47 log10 IU/mL | Standard Deviation 0.5 |
| LDV/SOF + RBV 12 Weeks (Group 1) | Change in HCV RNA From Baseline | Week 8 | -5.09 log10 IU/mL | Standard Deviation 0.583 |
| LDV/SOF 24 Weeks (Group 2) | Change in HCV RNA From Baseline | Week 4 | -5.06 log10 IU/mL | Standard Deviation 0.6 |
| LDV/SOF 24 Weeks (Group 2) | Change in HCV RNA From Baseline | Week 1 | -4.40 log10 IU/mL | Standard Deviation 0.535 |
| LDV/SOF 24 Weeks (Group 2) | Change in HCV RNA From Baseline | Week 8 | -5.08 log10 IU/mL | Standard Deviation 0.617 |
| LDV/SOF + RBV 24 Weeks (Group 3) | Change in HCV RNA From Baseline | Week 1 | -3.75 log10 IU/mL | Standard Deviation 0.878 |
| LDV/SOF + RBV 24 Weeks (Group 3) | Change in HCV RNA From Baseline | Week 8 | -4.47 log10 IU/mL | Standard Deviation 0.441 |
| LDV/SOF + RBV 24 Weeks (Group 3) | Change in HCV RNA From Baseline | Week 4 | -4.47 log10 IU/mL | Standard Deviation 0.441 |
Secondary
Percentage of Participants With HCV RNA < LLOQ While on Treatment
Time frame: Baseline to Week 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF + RBV 12 Weeks (Group 1) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 12 | 100.0 Percentage of participants |
| LDV/SOF + RBV 12 Weeks (Group 1) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 16 | NA Percentage of participants |
| LDV/SOF + RBV 12 Weeks (Group 1) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 24 | NA Percentage of participants |
| LDV/SOF + RBV 12 Weeks (Group 1) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 4 | 98.0 Percentage of participants |
| LDV/SOF + RBV 12 Weeks (Group 1) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 20 | NA Percentage of participants |
| LDV/SOF + RBV 12 Weeks (Group 1) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 8 | 100.0 Percentage of participants |
| LDV/SOF + RBV 12 Weeks (Group 1) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 1 | 23.5 Percentage of participants |
| LDV/SOF 24 Weeks (Group 2) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 12 | 100.0 Percentage of participants |
| LDV/SOF 24 Weeks (Group 2) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 1 | 31.7 Percentage of participants |
| LDV/SOF 24 Weeks (Group 2) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 4 | 95.1 Percentage of participants |
| LDV/SOF 24 Weeks (Group 2) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 16 | 97.6 Percentage of participants |
| LDV/SOF 24 Weeks (Group 2) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 8 | 100.0 Percentage of participants |
| LDV/SOF 24 Weeks (Group 2) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 24 | 100.0 Percentage of participants |
| LDV/SOF 24 Weeks (Group 2) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 20 | 97.6 Percentage of participants |
| LDV/SOF + RBV 24 Weeks (Group 3) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 24 | 100.0 Percentage of participants |
| LDV/SOF + RBV 24 Weeks (Group 3) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 20 | 100.0 Percentage of participants |
| LDV/SOF + RBV 24 Weeks (Group 3) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 1 | 0 Percentage of participants |
| LDV/SOF + RBV 24 Weeks (Group 3) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 4 | 100.0 Percentage of participants |
| LDV/SOF + RBV 24 Weeks (Group 3) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 8 | 100.0 Percentage of participants |
| LDV/SOF + RBV 24 Weeks (Group 3) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 12 | 100.0 Percentage of participants |
| LDV/SOF + RBV 24 Weeks (Group 3) | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 16 | 100.0 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 treatment, respectively.
Time frame: Posttreatment Weeks 4 and 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF + RBV 12 Weeks (Group 1) | Percentage of Participants With Sustained Virologic Response (SVR) at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 98.0 Percentage of participants |
| LDV/SOF + RBV 12 Weeks (Group 1) | Percentage of Participants With Sustained Virologic Response (SVR) at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 98.0 Percentage of participants |
| LDV/SOF 24 Weeks (Group 2) | Percentage of Participants With Sustained Virologic Response (SVR) at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 73.2 Percentage of participants |
| LDV/SOF 24 Weeks (Group 2) | Percentage of Participants With Sustained Virologic Response (SVR) at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 70.7 Percentage of participants |
| LDV/SOF + RBV 24 Weeks (Group 3) | 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 + RBV 24 Weeks (Group 3) | 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 |
Secondary
Percentage of Participants With Virologic Failure
Virologic failure was defined as: * On-treatment virologic failure: * Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment), or * Rebound (confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or * Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) * Virologic relapse: * Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit confirmed with 2 consecutive values or last available posttreatment measurement
Time frame: Up to posttreatment Week 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF + RBV 12 Weeks (Group 1) | Percentage of Participants With Virologic Failure | On treatment Virologic Failure | 0 Percentage of participants |
| LDV/SOF + RBV 12 Weeks (Group 1) | Percentage of Participants With Virologic Failure | Relapse | 2.0 Percentage of participants |
| LDV/SOF 24 Weeks (Group 2) | Percentage of Participants With Virologic Failure | On treatment Virologic Failure | 2.4 Percentage of participants |
| LDV/SOF 24 Weeks (Group 2) | Percentage of Participants With Virologic Failure | Relapse | 27.5 Percentage of participants |
| LDV/SOF + RBV 24 Weeks (Group 3) | Percentage of Participants With Virologic Failure | On treatment Virologic Failure | 0 Percentage of participants |
| LDV/SOF + RBV 24 Weeks (Group 3) | Percentage of Participants With Virologic Failure | Relapse | 0 Percentage of participants |