Chronic HCV Infection
Conditions
Brief summary
This study will evaluate the antiviral efficacy of sofosbuvir (SOF)/ledipasvir (LDV) fixed-dose combination (FDC) tablet with or without ribavirin (RBV) in treatment-naive or treatment-experienced Japanese participants with chronic genotype 1 HCV infection. Participants receive 12 weeks of treatment and continue assessments during a 24-week posttreatment follow-up period.
Interventions
DRUGLDV/SOF
LDV/SOF 90/400 mg FDC tablet administered orally once daily
DRUGRBV
RBV tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (≤ 60 kg = 600 mg, \> 60 kg to ≤ 80 kg = 800 mg, and ≥ 80 kg = 1000 mg)
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Body weight ≥ 40 kg * HCV RNA ≥ 10\^5 IU/mL at screening
Exclusion criteria
* Current or prior history of any clinically-significant illness (other than HCV) * Pregnant or nursing female or male with pregnant female partner * Chronic liver disease of a non-HCV etiology * Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12), Treatment-naive, Noncirrhotic Participants | Posttreatment Week 12 | SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment. |
| Percentage of Participants With Sustained Virologic Response at 12 Weeks After Discontinuation of Therapy (SVR12) | Posttreatment Week 12 | SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment. |
| Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | Up to 12 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | Posttreatment Weeks 4 and 24 | SVR4 and SVR 24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively. |
| Percentage of Participants Experiencing 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. |
Countries
Japan
Participant flow
Recruitment details
Participants were enrolled study sites in Japan. The first participant was screened on 15 October 2013. The last study visit occurred on 22 August 2014.
Pre-assignment details
421 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| LDV/SOF (Treatment Naive) Treatment-naive participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks. | 83 |
| LDV/SOF+RBV (Treatment Naive) Treatment-naive participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks. | 83 |
| LDV/SOF (Treatment Experienced) Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks. | 88 |
| LDV/SOF+RBV (Treatment Experienced) Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks. | 87 |
| Total | 341 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | LDV/SOF (Treatment Experienced) | LDV/SOF (Treatment Naive) | LDV/SOF+RBV (Treatment Naive) | LDV/SOF+RBV (Treatment Experienced) |
|---|---|---|---|---|---|
| Age, Continuous | 59 years STANDARD_DEVIATION 9.4 | 61 years STANDARD_DEVIATION 8.5 | 59 years STANDARD_DEVIATION 9.9 | 59 years STANDARD_DEVIATION 10.3 | 59 years STANDARD_DEVIATION 8.7 |
| Age, Customized < 65 years | 229 participants | 51 participants | 60 participants | 55 participants | 63 participants |
| Age, Customized ≥ 65 years | 112 participants | 37 participants | 23 participants | 28 participants | 24 participants |
| Cirrhosis Status No | 265 participants | 60 participants | 70 participants | 71 participants | 64 participants |
| Cirrhosis Status Yes | 76 participants | 28 participants | 13 participants | 12 participants | 23 participants |
| HCV RNA Category < 800,000 IU/mL | 37 participants | 10 participants | 6 participants | 8 participants | 13 participants |
| HCV RNA Category ≥ 800,000 IU/mL | 304 participants | 78 participants | 77 participants | 75 participants | 74 participants |
| Hepatitis C Virus (HCV) RNA | 6.6 log10 IU/mL STANDARD_DEVIATION 0.53 | 6.6 log10 IU/mL STANDARD_DEVIATION 0.55 | 6.6 log10 IU/mL STANDARD_DEVIATION 0.48 | 6.6 log10 IU/mL STANDARD_DEVIATION 0.54 | 6.5 log10 IU/mL STANDARD_DEVIATION 0.54 |
| IL28b Status CC | 165 participants | 33 participants | 53 participants | 46 participants | 33 participants |
| IL28b Status CT | 160 participants | 49 participants | 29 participants | 31 participants | 51 participants |
| IL28b Status TT | 16 participants | 6 participants | 1 participants | 6 participants | 3 participants |
| Race/Ethnicity, Customized Japanese | 341 participants | 88 participants | 83 participants | 83 participants | 87 participants |
| Response to Prior HCV Treatment IFN Intolerant | NA participants | 15 participants | NA participants | NA participants | 15 participants |
| Response to Prior HCV Treatment Nonresponder | NA participants | 29 participants | NA participants | NA participants | 28 participants |
| Response to Prior HCV Treatment Relapse/Breakthrough | NA participants | 44 participants | NA participants | NA participants | 44 participants |
| Sex: Female, Male Female | 199 Participants | 52 Participants | 50 Participants | 49 Participants | 48 Participants |
| Sex: Female, Male Male | 142 Participants | 36 Participants | 33 Participants | 34 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 77 / 171 | 90 / 170 |
| serious Total, serious adverse events | 3 / 171 | 2 / 170 |
Outcome results
Primary
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Time frame: Up to 12 weeks
Population: Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF (Treatment Naive) | Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | 0 percentage of participants |
| LDV/SOF+RBV (Treatment Naive) | Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | 1.8 percentage of participants |
Primary
Percentage of Participants With Sustained Virologic Response at 12 Weeks After Discontinuation of Therapy (SVR12)
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
Time frame: Posttreatment Week 12
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF (Treatment Naive) | Percentage of Participants With Sustained Virologic Response at 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 percentage of participants |
| LDV/SOF+RBV (Treatment Naive) | Percentage of Participants With Sustained Virologic Response at 12 Weeks After Discontinuation of Therapy (SVR12) | 96.4 percentage of participants |
| LDV/SOF (Treatment Experienced) | Percentage of Participants With Sustained Virologic Response at 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 percentage of participants |
| LDV/SOF+RBV (Treatment Experienced) | Percentage of Participants With Sustained Virologic Response at 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 percentage of participants |
95% CI: [-10.2, 1]
95% CI: [-4.2, 4.2]
Primary
Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12), Treatment-naive, Noncirrhotic Participants
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
Time frame: Posttreatment Week 12
Population: Treatment-naive participants in the Full Analysis Set (randomized, received at least 1 dose of study drug, and had chronic genotype 1 (1a, 1b, or mixed 1a/1b) HCV infection) without cirrhosis were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF (Treatment Naive) | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12), Treatment-naive, Noncirrhotic Participants | 100.0 percentage of participants |
| LDV/SOF+RBV (Treatment Naive) | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12), Treatment-naive, Noncirrhotic Participants | 97.2 percentage of participants |
p-value: <0.001Binomial test
p-value: <0.001Binomial test
Secondary
Percentage of Participants Experiencing 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.
Time frame: Up to Posttreatment Week 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF (Treatment Naive) | Percentage of Participants Experiencing Virologic Failure | On-treatment virologic failure | 0 percentage of participants |
| LDV/SOF (Treatment Naive) | Percentage of Participants Experiencing Virologic Failure | Virologic relapse | 0 percentage of participants |
| LDV/SOF+RBV (Treatment Naive) | Percentage of Participants Experiencing Virologic Failure | Virologic relapse | 1.2 percentage of participants |
| LDV/SOF+RBV (Treatment Naive) | Percentage of Participants Experiencing Virologic Failure | On-treatment virologic failure | 0 percentage of participants |
| LDV/SOF (Treatment Experienced) | Percentage of Participants Experiencing Virologic Failure | Virologic relapse | 0 percentage of participants |
| LDV/SOF (Treatment Experienced) | Percentage of Participants Experiencing Virologic Failure | On-treatment virologic failure | 0 percentage of participants |
| LDV/SOF+RBV (Treatment Experienced) | Percentage of Participants Experiencing Virologic Failure | Virologic relapse | 0 percentage of participants |
| LDV/SOF+RBV (Treatment Experienced) | Percentage of Participants Experiencing Virologic Failure | On-treatment virologic failure | 0 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4 and SVR 24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
Time frame: Posttreatment Weeks 4 and 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF (Treatment Naive) | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 100.0 percentage of participants |
| LDV/SOF (Treatment Naive) | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 100.0 percentage of participants |
| LDV/SOF+RBV (Treatment Naive) | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 96.4 percentage of participants |
| LDV/SOF+RBV (Treatment Naive) | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 96.4 percentage of participants |
| LDV/SOF (Treatment Experienced) | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 100.0 percentage of participants |
| LDV/SOF (Treatment Experienced) | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 100.0 percentage of participants |
| LDV/SOF+RBV (Treatment Experienced) | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 100.0 percentage of participants |
| LDV/SOF+RBV (Treatment Experienced) | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 100.0 percentage of participants |