Hepatitis C
Conditions
Brief summary
This study will evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir plus ribavirin administered for 16 weeks and 24 weeks in participants with chronic genotype 1 (GT1) or genotype 3 (GT3) hepatitis C virus (HCV) infection.
Interventions
DRUGSOF
Sofosbuvir (SOF) 400 mg tablet administered orally once daily
DRUGRBV
Ribavirin (RBV) tablets administered orally in a divided daily dose using weight-based dosing (\< 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
* Confirmed chronic genotype 1 or 3 HCV infection * HCV treatment-naive * Individuals will have cirrhosis status assessment; liver biopsy may be required. * Screening laboratory values within predefined 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 * Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) * Contraindication to ribavirin therapy * Excessive alcohol ingestion as defined by protocol * History of solid organ transplantation * Current or prior history of clinical hepatic decompensation * History of clinically significant illness or any other medical disorder that may interfere with the individual's 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) at 12 weeks after stopping study treatment. |
| Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | Up to 24 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 On-treatment Virologic Failure | Up to 24 weeks | On-treatment virologic failure was defined as * 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) |
| Percentage of Participants Experiencing Virologic Relapse | Up to Posttreatment Week 12 | Virologic relapse was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit. |
Countries
Russia
Participant flow
Recruitment details
Participants were enrolled at a total of 16 study sites in Russia. The first participant was screened on 06 June 2013. The last study visit occurred on 27 July 2014.
Pre-assignment details
139 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| SOF+RBV 16 Weeks, GT1 SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 16 weeks (genotype 1) | 32 |
| SOF+RBV 24 Weeks, GT1 SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (genotype 1) | 34 |
| SOF+RBV 16 Weeks, GT3 SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 16 weeks (genotype 3) | 30 |
| SOF+RBV 24 Weeks, GT3 SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (genotype 3) | 31 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 20 | 11 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrew Consent | 1 | 0 |
Baseline characteristics
| Characteristic | SOF+RBV 16 Weeks, GT1 | SOF+RBV 24 Weeks, GT1 | SOF+RBV 16 Weeks, GT3 | SOF+RBV 24 Weeks, GT3 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 41 years STANDARD_DEVIATION 12.8 | 42 years STANDARD_DEVIATION 9.8 | 38 years STANDARD_DEVIATION 8.2 | 40 years STANDARD_DEVIATION 9.6 | 40 years STANDARD_DEVIATION 10.3 |
| Cirrhosis Status Missing | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Cirrhosis Status No | 28 participants | 28 participants | 23 participants | 26 participants | 105 participants |
| Cirrhosis Status Yes | 4 participants | 6 participants | 6 participants | 5 participants | 21 participants |
| HCV RNA | 6.2 log10 IU/mL STANDARD_DEVIATION 0.6 | 6.1 log10 IU/mL STANDARD_DEVIATION 0.6 | 6.2 log10 IU/mL STANDARD_DEVIATION 0.81 | 6.2 log10 IU/mL STANDARD_DEVIATION 0.77 | 6.2 log10 IU/mL STANDARD_DEVIATION 0.69 |
| HCV RNA Category < 800,000 IU/mL | 12 participants | 11 participants | 10 participants | 10 participants | 43 participants |
| HCV RNA Category ≥ 800,000 IU/mL | 20 participants | 23 participants | 20 participants | 21 participants | 84 participants |
| IL28b Status CC | 10 participants | 6 participants | 12 participants | 15 participants | 43 participants |
| IL28b Status CT | 19 participants | 23 participants | 16 participants | 15 participants | 73 participants |
| IL28b Status TT | 3 participants | 5 participants | 2 participants | 1 participants | 11 participants |
| Race/Ethnicity, Customized White | 32 participants | 34 participants | 30 participants | 31 participants | 127 participants |
| Sex: Female, Male Female | 19 Participants | 18 Participants | 11 Participants | 12 Participants | 60 Participants |
| Sex: Female, Male Male | 13 Participants | 16 Participants | 19 Participants | 19 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 62 | 21 / 65 |
| serious Total, serious adverse events | 1 / 62 | 1 / 65 |
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 24 weeks
Population: Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV 16 Weeks, GT1 | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 0 percentage of participants |
| SOF+RBV 24 Weeks, GT1 | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 0 percentage of participants |
| SOF+RBV 16 Weeks, GT3 | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 0 percentage of participants |
| SOF+RBV 24 Weeks, GT3 | 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 with genotype 1 or 3 HCV infection who were randomized and received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV 16 Weeks, GT1 | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 50.0 percentage of participants |
| SOF+RBV 24 Weeks, GT1 | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 76.5 percentage of participants |
| SOF+RBV 16 Weeks, GT3 | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 86.7 percentage of participants |
| SOF+RBV 24 Weeks, GT3 | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 90.3 percentage of participants |
Secondary
Percentage of Participants Experiencing On-treatment Virologic Failure
On-treatment virologic failure was defined as * 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)
Time frame: Up to 24 weeks
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV 16 Weeks, GT1 | Percentage of Participants Experiencing On-treatment Virologic Failure | 0 percentage of participants |
| SOF+RBV 24 Weeks, GT1 | Percentage of Participants Experiencing On-treatment Virologic Failure | 0 percentage of participants |
| SOF+RBV 16 Weeks, GT3 | Percentage of Participants Experiencing On-treatment Virologic Failure | 0 percentage of participants |
| SOF+RBV 24 Weeks, GT3 | Percentage of Participants Experiencing On-treatment Virologic Failure | 0 percentage of participants |
Secondary
Percentage of Participants Experiencing Virologic Relapse
Virologic relapse was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit.
Time frame: Up to Posttreatment Week 12
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV 16 Weeks, GT1 | Percentage of Participants Experiencing Virologic Relapse | 50.0 percentage of participants |
| SOF+RBV 24 Weeks, GT1 | Percentage of Participants Experiencing Virologic Relapse | 23.5 percentage of participants |
| SOF+RBV 16 Weeks, GT3 | Percentage of Participants Experiencing Virologic Relapse | 13.3 percentage of participants |
| SOF+RBV 24 Weeks, GT3 | Percentage of Participants Experiencing Virologic Relapse | 9.7 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 16 Weeks, GT1 | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 53.1 percentage of participants |
| SOF+RBV 16 Weeks, GT1 | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 46.9 percentage of participants |
| SOF+RBV 24 Weeks, GT1 | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 76.5 percentage of participants |
| SOF+RBV 24 Weeks, GT1 | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 76.5 percentage of participants |
| SOF+RBV 16 Weeks, GT3 | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 90.0 percentage of participants |
| SOF+RBV 16 Weeks, GT3 | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 86.7 percentage of participants |
| SOF+RBV 24 Weeks, GT3 | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 90.3 percentage of participants |
| SOF+RBV 24 Weeks, GT3 | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 90.3 percentage of participants |