Hepatitis C Virus
Conditions
Brief summary
This study is to evaluate the safety, tolerability, and antiviral activity of sofosbuvir (SOF) with ribavirin (RBV) in Egyptian adults with chronic genotype 4 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 according to package insert weight-based dosing recommendations (\< 75kg = 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
* First generation Egyptian; must have been born in Egypt and can trace both maternal and paternal Egyptian ancestry * Treatment-experienced or treatment-naive * Chronic genotype 4 HCV infection * Not co-infected with HIV * Screening laboratory values within defined thresholds * Use of highly effective contraception methods * Must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments
Exclusion criteria
* History of any other clinically significant chronic liver disease * Pregnant or nursing female or male with pregnant female partner * History of clinically-significant illness or any other major medical disorder that may interfere with treatment, assessment, or compliance with the protocol * Excessive alcohol ingestion or significant drug abuse
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 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 SVR24 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: 1. Viral breakthrough: 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, or 2. Viral rebound: \> 1 log10 IU/mL increase in HCV RNA from nadir 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, or 3. Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment |
| 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
United States
Participant flow
Recruitment details
Participants were enrolled at one study site in the United States. The first participant was screened on 01 October 2012. The last participant observation occurred on 12 February 2014.
Pre-assignment details
76 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| SOF+RBV 12 Wk TN SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks (treatment naive (TN)) | 14 |
| SOF+RBV 12 Wk TE SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks (treatment experienced (TE)) | 17 |
| SOF+RBV 24 Wk TN SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (treatment naive) | 14 |
| SOF+RBV 24 Wk TE SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (treatment experienced) | 15 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 10 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 |
Baseline characteristics
| Characteristic | SOF+RBV 12 Wk TN | Total | SOF+RBV 24 Wk TE | SOF+RBV 24 Wk TN | SOF+RBV 12 Wk TE |
|---|---|---|---|---|---|
| Age, Continuous | 53 years STANDARD_DEVIATION 12.4 | 54 years STANDARD_DEVIATION 12.2 | 57 years STANDARD_DEVIATION 9.9 | 52 years STANDARD_DEVIATION 15.6 | 54 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 60 Participants | 15 Participants | 14 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| HCV RNA Category < 800,000 IU/mL | 7 participants | 26 participants | 7 participants | 8 participants | 4 participants |
| HCV RNA Category ≥ 800,000 IU/mL | 7 participants | 34 participants | 8 participants | 6 participants | 13 participants |
| HCV RNA (log10 IU/mL) | 5.7 log10 IU/mL STANDARD_DEVIATION 0.59 | 6.0 log10 IU/mL STANDARD_DEVIATION 0.61 | 6.1 log10 IU/mL STANDARD_DEVIATION 0.45 | 5.9 log10 IU/mL STANDARD_DEVIATION 0.74 | 6.2 log10 IU/mL STANDARD_DEVIATION 0.58 |
| IL28b Status CC | 3 participants | 10 participants | 0 participants | 6 participants | 1 participants |
| IL28b Status CT | 9 participants | 39 participants | 12 participants | 7 participants | 11 participants |
| IL28b Status TT | 2 participants | 11 participants | 3 participants | 1 participants | 5 participants |
| Liver Cirrhosis No | 11 participants | 46 participants | 11 participants | 11 participants | 13 participants |
| Liver Cirrhosis Yes | 3 participants | 14 participants | 4 participants | 3 participants | 4 participants |
| Race/Ethnicity, Customized White | 14 participants | 60 participants | 15 participants | 14 participants | 17 participants |
| Sex: Female, Male Female | 6 Participants | 19 Participants | 1 Participants | 9 Participants | 3 Participants |
| Sex: Female, Male Male | 8 Participants | 41 Participants | 14 Participants | 5 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 28 / 31 | 29 / 29 |
| serious Total, serious adverse events | 0 / 31 | 3 / 29 |
Outcome results
Primary
Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)
The percentage of participants 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 12 Wk TN | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 0 percentage of participants |
| SOF+RBV 12 Wk TE | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 3.4 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 4 HCV infection who were randomized into the study and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV 12 Wk TN | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 78.6 percentage of participants |
| SOF+RBV 12 Wk TE | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 58.8 percentage of participants |
| SOF+RBV 24 Wk TN | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 percentage of participants |
| SOF+RBV 24 Wk TE | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 86.7 percentage of participants |
Secondary
Percentage of Participants Experiencing On-treatment Virologic Failure
On-treatment virologic failure was defined as: 1. Viral breakthrough: 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, or 2. Viral rebound: \> 1 log10 IU/mL increase in HCV RNA from nadir 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, or 3. Nonresponse: 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 12 Wk TN | Percentage of Participants Experiencing On-treatment Virologic Failure | 7.1 percentage of participants |
| SOF+RBV 12 Wk TE | Percentage of Participants Experiencing On-treatment Virologic Failure | 0 percentage of participants |
| SOF+RBV 24 Wk TN | Percentage of Participants Experiencing On-treatment Virologic Failure | 0 percentage of participants |
| SOF+RBV 24 Wk TE | Percentage of Participants Experiencing On-treatment Virologic Failure | 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: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV 12 Wk TN | Percentage of Participants Experiencing Viral Relapse | 15.4 percentage of participants |
| SOF+RBV 12 Wk TE | Percentage of Participants Experiencing Viral Relapse | 41.2 percentage of participants |
| SOF+RBV 24 Wk TN | Percentage of Participants Experiencing Viral Relapse | 0 percentage of participants |
| SOF+RBV 24 Wk TE | Percentage of Participants Experiencing Viral Relapse | 13.3 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 SVR24 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 12 Wk TN | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 78.6 percentage of participants |
| SOF+RBV 12 Wk TN | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 78.6 percentage of participants |
| SOF+RBV 12 Wk TE | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 58.8 percentage of participants |
| SOF+RBV 12 Wk TE | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 58.8 percentage of participants |
| SOF+RBV 24 Wk TN | 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 |
| SOF+RBV 24 Wk TN | 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 |
| SOF+RBV 24 Wk TE | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 93.3 percentage of participants |
| SOF+RBV 24 Wk TE | 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 |