Hepatitis C
Conditions
Keywords
HCV genotype 2 (GT-2)
Brief summary
This study will evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir (SOF) plus ribavirin (RBV) in Japanese participants with chronic genotype 2 hepatitis C virus (HCV) infection.
Interventions
DRUGSofosbuvir
Sofosbuvir 400 mg tablet administered orally once daily
DRUGRBV
Ribavirin (RBV) tablets were administered orally in a divided daily dose according to package insert weight-based dosing according to the approved Copegus labeling in Japan (\< 60 kg = 600 mg , \> 60 kg to ≤ 80 kg = 800 mg, and ≥ 80 kg = 1000 mg)
Sponsors
Gilead Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chronic genotype 2 HCV-infection * Male or female, age ≥ 20 years * Body weight ≥ 40 kg * HCV RNA ≥ 10,000 IU/mL at screening
Exclusion criteria
* Current or prior history of 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) | 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. |
| Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | Up to 12 weeks | The percentage of participants permanently discontinuing any study drug due to an adverse event was summarized. |
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 following the last dose of study drug, respectively. |
| Percentage of Participants Experiencing Viral Breakthrough | Up to 12 weeks | Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values. |
| Percentage of Participants Experiencing Viral Relapse | Up to Posttreatment Week 24 | Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA \< LLOQ) at end of treatment, but did not achieve an SVR. |
Countries
Japan
Participant flow
Recruitment details
Participants were enrolled at a total of 20 study sites in Japan. The first participant was screened on 28 June 2013. The last study visit occurred on 09 June 2014.
Pre-assignment details
188 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| SOF+RBV Treatment Naive SOF 400 mg tablet once daily + RBV tablets (600-1000 mg daily based on weight) for 12 weeks (treatment naive) | 90 |
| SOF+RBV Treatment Experienced SOF 400 mg tablet once daily + RBV tablets (600-1000 mg daily based on weight) for 12 weeks (treatment experienced) | 63 |
| Total | 153 |
Baseline characteristics
| Characteristic | SOF+RBV Treatment Naive | Total | SOF+RBV Treatment Experienced |
|---|---|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 10.6 | 57 years STANDARD_DEVIATION 10.1 | 60 years STANDARD_DEVIATION 8.8 |
| Cirrhosis Status No | 82 participants | 136 participants | 54 participants |
| Cirrhosis Status Yes | 8 participants | 17 participants | 9 participants |
| HCV RNA | 6.2 log10 IU/mL STANDARD_DEVIATION 0.92 | 6.3 log10 IU/mL STANDARD_DEVIATION 0.84 | 6.5 log10 IU/mL STANDARD_DEVIATION 0.66 |
| HCV RNA Category < 800,000 IU/mL | 26 participants | 38 participants | 12 participants |
| HCV RNA Category ≥ 800,000 IU/mL | 64 participants | 115 participants | 51 participants |
| IL28b Status CC | 73 participants | 121 participants | 48 participants |
| IL28b Status CT | 17 participants | 28 participants | 11 participants |
| IL28b Status TT | 0 participants | 4 participants | 4 participants |
| Sex: Female, Male Female | 57 Participants | 83 Participants | 26 Participants |
| Sex: Female, Male Male | 33 Participants | 70 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 69 / 153 |
| serious Total, serious adverse events | 2 / 153 |
Outcome results
Primary
Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)
The percentage of participants permanently discontinuing any study drug due to an adverse event was summarized.
Time frame: Up to 12 weeks
Population: Safety Analysis Set: participants who were enrolled and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV Treatment Naive | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 0 percentage of 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) at 12 weeks after stopping study treatment.
Time frame: Posttreatment Week 12
Population: Full Analysis Set: participants who were enrolled, received at least 1 dose of study drug, and had chronic genotype 2 HCV infection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV Treatment Naive | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 97.8 percentage of participants |
| SOF+RBV Treatment Experienced | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 95.2 percentage of participants |
Secondary
Percentage of Participants Experiencing Viral Breakthrough
Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values.
Time frame: Up to 12 weeks
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV Treatment Naive | Percentage of Participants Experiencing Viral Breakthrough | 0 percentage of participants |
| SOF+RBV Treatment Experienced | Percentage of Participants Experiencing Viral Breakthrough | 0 percentage of participants |
Secondary
Percentage of Participants Experiencing Viral Relapse
Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA \< LLOQ) at end of treatment, but did not achieve an SVR.
Time frame: Up to Posttreatment Week 24
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV Treatment Naive | Percentage of Participants Experiencing Viral Relapse | 2.2 percentage of participants |
| SOF+RBV Treatment Experienced | Percentage of Participants Experiencing Viral Relapse | 4.8 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 following the last dose of study drug, respectively.
Time frame: Posttreatment Weeks 4 and 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF+RBV Treatment Naive | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 98.9 percentage of participants |
| SOF+RBV Treatment Naive | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 97.8 percentage of participants |
| SOF+RBV Treatment Experienced | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 95.2 percentage of participants |
| SOF+RBV Treatment Experienced | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 95.2 percentage of participants |