Chronic Hepatitis C Virus
Conditions
Keywords
HCV genotype 1 (GT-1), HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, GS-7977, GS-5885, Ribavirin, Open Label, Sofosbuvir, Treatment-Naïve, Protease Inhibitors, PI
Brief summary
This study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) with or without ribavirin (RBV), administered for 8 or 12 weeks of treatment in participants with chronic genotype 1 hepatitis C virus (HCV) infection who are treatment-naive, and for 12 weeks in participants who had previously received a regimen containing a protease inhibitor for the treatment of HCV.
Interventions
DRUGLDV/SOF
LDV 90 mg/SOF 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 (\< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years, with chronic genotype 1 HCV infection * HCV RNA equal to or greater than 10,000 IU/mL at screening * Cirrhosis determination; a liver biopsy may be required * Screening laboratory values within defined thresholds * Use of two effective contraception methods if female of childbearing potential or sexually active male
Exclusion criteria
* Pregnant or nursing female or male with pregnant female partner * Current or prior history of clinical hepatic decompensation * Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers) * Chronic use of systemic immunosuppressive agents * History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response (SVR) 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) 12 weeks after stopping study treatment. |
| Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | Baseline to Week 12 | The number of participants experiencing an adverse event leading to permanent discontinuation of study drug(s) was summarized. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | Posttreatment Weeks 2, 4, 8, and 24 | SVR2, SVR4, SVR8, and SVR24 was defined as HCV RNA \< LLOQ at 2, 4, 8, and 24 weeks following the last dose of study drug, respectively. |
| Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse | Baseline to Posttreatment Week 24 | * Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while receiving treatment, confirmed with 2 consecutive values (second confirmation value could be posttreatment), or last available on-treatment measurement with no subsequent follow-up values. * Viral relapse was defined as 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. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 1 study site in the United States. The first participant was screened on 22 October 2012. The last participant observation was on 13 January 2014.
Pre-assignment details
116 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| LDV/SOF 8 Weeks (TN) Treatment-naive participants were randomized to receive LDV 90 mg/SOF 400 mg for 8 weeks. | 20 |
| LDV/SOF+RBV 8 Weeks (TN) Treatment-naive participants were randomized to receive LDV 90 mg/SOF 400 mg plus weight-based RBV (1000-1200 mg) for 8 weeks. | 21 |
| LDV/SOF 12 Weeks (TN) Treatment-naive participants were randomized to receive LDV 90 mg/SOF 400 mg for 12 weeks. | 19 |
| LDV/SOF 12 Weeks (TE) Treatment-experienced participants (had virologic failure following prior therapy with a PI+PEG+RBV regimen) were randomized to receive LDV 90 mg/SOF 400 mg for 12 weeks. | 19 |
| LDV/SOF+RBV 12 Weeks (TE) Treatment-experienced participants (had virologic failure following prior therapy with a PI+PEG+RBV regimen) were randomized to receive LDV 90 mg/SOF 400 mg plus weight-based RBV (1000-1200 mg) for 12 weeks. | 21 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | LDV/SOF 8 Weeks (TN) | Total | LDV/SOF+RBV 12 Weeks (TE) | LDV/SOF 12 Weeks (TE) | LDV/SOF 12 Weeks (TN) | LDV/SOF+RBV 8 Weeks (TN) |
|---|---|---|---|---|---|---|
| Age, Continuous | 48 years STANDARD_DEVIATION 10.7 | 50 years STANDARD_DEVIATION 10.4 | 52 years STANDARD_DEVIATION 9.8 | 54 years STANDARD_DEVIATION 6.6 | 46 years STANDARD_DEVIATION 11.6 | 50 years STANDARD_DEVIATION 11.1 |
| Cirrhosis No | 20 participants | 78 participants | 10 participants | 8 participants | 19 participants | 21 participants |
| Cirrhosis Yes | 0 participants | 22 participants | 11 participants | 11 participants | 0 participants | 0 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 40 Participants | 10 Participants | 6 Participants | 9 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 60 Participants | 11 Participants | 13 Participants | 10 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| HCV RNA Category < 800,000 IU/mL | 9 participants | 32 participants | 5 participants | 4 participants | 7 participants | 7 participants |
| HCV RNA Category ≥ 800,000 IU/mL | 11 participants | 68 participants | 16 participants | 15 participants | 12 participants | 14 participants |
| HCV RNA (log10 IU/mL) | 6.1 log10 IU/mL STANDARD_DEVIATION 0.82 | 6.1 log10 IU/mL STANDARD_DEVIATION 0.69 | 6.2 log10 IU/mL STANDARD_DEVIATION 0.42 | 6.3 log10 IU/mL STANDARD_DEVIATION 0.49 | 6.1 log10 IU/mL STANDARD_DEVIATION 0.79 | 6.0 log10 IU/mL STANDARD_DEVIATION 0.84 |
| Hepatitis C Virus (HCV) Genotype 1a | 17 participants | 87 participants | 16 participants | 18 participants | 17 participants | 19 participants |
| Hepatitis C Virus (HCV) Genotype 1b | 3 participants | 13 participants | 5 participants | 1 participants | 2 participants | 2 participants |
| IL28b Status CC | 4 participants | 15 participants | 1 participants | 2 participants | 1 participants | 7 participants |
| IL28b Status CT | 12 participants | 61 participants | 11 participants | 13 participants | 14 participants | 11 participants |
| IL28b Status TT | 4 participants | 24 participants | 9 participants | 4 participants | 4 participants | 3 participants |
| Prior HCV Treatment and Response Non-responder to PI boceprevir | 0 participants | 18 participants | 9 participants | 9 participants | 0 participants | 0 participants |
| Prior HCV Treatment and Response Non-responder to PI telaprevir | 0 participants | 9 participants | 6 participants | 3 participants | 0 participants | 0 participants |
| Prior HCV Treatment and Response Relapse/Breakthrough to PI boceprevir | 0 participants | 4 participants | 2 participants | 2 participants | 0 participants | 0 participants |
| Prior HCV Treatment and Response Relapse/Breakthrough to PI telaprevir | 0 participants | 9 participants | 4 participants | 5 participants | 0 participants | 0 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 9 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 88 Participants | 19 Participants | 16 Participants | 17 Participants | 21 Participants |
| Sex: Female, Male Female | 6 Participants | 34 Participants | 7 Participants | 4 Participants | 8 Participants | 9 Participants |
| Sex: Female, Male Male | 14 Participants | 66 Participants | 14 Participants | 15 Participants | 11 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 20 | 12 / 21 | 8 / 19 | 7 / 19 | 12 / 21 |
| serious Total, serious adverse events | 0 / 20 | 1 / 21 | 1 / 19 | 1 / 19 | 1 / 21 |
Outcome results
Primary
Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)
The number of participants experiencing an adverse event leading to permanent discontinuation of study drug(s) was summarized.
Time frame: Baseline to Week 12
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF 8 Weeks (TN) | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 0 participants |
| LDV/SOF+RBV 8 Weeks (TN) | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 0 participants |
| LDV/SOF 12 Weeks (TN) | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 0 participants |
| LDV/SOF 12 Weeks (TE) | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 0 participants |
| LDV/SOF+RBV 12 Weeks (TE) | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 0 participants |
Primary
Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) 12 weeks after stopping study treatment.
Time frame: Posttreatment Week 12
Population: Full Analysis Set: participants were randomized and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF 8 Weeks (TN) | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 95.0 percentage of participants |
| LDV/SOF+RBV 8 Weeks (TN) | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 percentage of participants |
| LDV/SOF 12 Weeks (TN) | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 94.7 percentage of participants |
| LDV/SOF 12 Weeks (TE) | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 94.7 percentage of participants |
| LDV/SOF+RBV 12 Weeks (TE) | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 percentage of participants |
Secondary
Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse
* Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while receiving treatment, confirmed with 2 consecutive values (second confirmation value could be posttreatment), or last available on-treatment measurement with no subsequent follow-up values. * Viral relapse was defined as 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: Baseline to Posttreatment Week 24
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF 8 Weeks (TN) | Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse | Viral breakthrough | 0 percentage of participants |
| LDV/SOF 8 Weeks (TN) | Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse | Viral relapse | 5.0 percentage of participants |
| LDV/SOF+RBV 8 Weeks (TN) | Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse | Viral breakthrough | 0 percentage of participants |
| LDV/SOF+RBV 8 Weeks (TN) | Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse | Viral relapse | 0 percentage of participants |
| LDV/SOF 12 Weeks (TN) | Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse | Viral breakthrough | 0 percentage of participants |
| LDV/SOF 12 Weeks (TN) | Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse | Viral relapse | 0 percentage of participants |
| LDV/SOF 12 Weeks (TE) | Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse | Viral relapse | 5.3 percentage of participants |
| LDV/SOF 12 Weeks (TE) | Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse | Viral breakthrough | 0 percentage of participants |
| LDV/SOF+RBV 12 Weeks (TE) | Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse | Viral breakthrough | 0 percentage of participants |
| LDV/SOF+RBV 12 Weeks (TE) | Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse | Viral relapse | 0 percentage of participants |
Secondary
Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24)
SVR2, SVR4, SVR8, and SVR24 was defined as HCV RNA \< LLOQ at 2, 4, 8, and 24 weeks following the last dose of study drug, respectively.
Time frame: Posttreatment Weeks 2, 4, 8, and 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF 8 Weeks (TN) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR2 | 100.0 percentage of participants |
| LDV/SOF 8 Weeks (TN) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR4 | 100.0 percentage of participants |
| LDV/SOF 8 Weeks (TN) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR8 | 95.0 percentage of participants |
| LDV/SOF 8 Weeks (TN) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR24 | 95.0 percentage of participants |
| LDV/SOF+RBV 8 Weeks (TN) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR2 | 100.0 percentage of participants |
| LDV/SOF+RBV 8 Weeks (TN) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR24 | 100.0 percentage of participants |
| LDV/SOF+RBV 8 Weeks (TN) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR4 | 100.0 percentage of participants |
| LDV/SOF+RBV 8 Weeks (TN) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR8 | 100.0 percentage of participants |
| LDV/SOF 12 Weeks (TN) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR24 | 94.7 percentage of participants |
| LDV/SOF 12 Weeks (TN) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR4 | 100.0 percentage of participants |
| LDV/SOF 12 Weeks (TN) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR8 | 100.0 percentage of participants |
| LDV/SOF 12 Weeks (TN) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR2 | 100.0 percentage of participants |
| LDV/SOF 12 Weeks (TE) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR2 | 94.7 percentage of participants |
| LDV/SOF 12 Weeks (TE) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR4 | 94.7 percentage of participants |
| LDV/SOF 12 Weeks (TE) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR24 | 94.7 percentage of participants |
| LDV/SOF 12 Weeks (TE) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR8 | 94.7 percentage of participants |
| LDV/SOF+RBV 12 Weeks (TE) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR24 | 100.0 percentage of participants |
| LDV/SOF+RBV 12 Weeks (TE) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR8 | 100.0 percentage of participants |
| LDV/SOF+RBV 12 Weeks (TE) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR4 | 100.0 percentage of participants |
| LDV/SOF+RBV 12 Weeks (TE) | Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) | SVR2 | 100.0 percentage of participants |