Hepatitis C Virus
Conditions
Keywords
Liver Diseases, Digestive System Diseases, Hepatitis, Viral, Human, Virus Diseases, Enterovirus Infections, Picornaviridae Infections, RNA Virus Infections, Flaviviridae Infections, Antiviral Agents, Anti-Infective Agents, Therapeutic Uses, Pharmacologic Actions, Antimetabolites, Molecular Mechanisms of Pharmacological Action, HCV genotype 4 (GT-4), HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, GS-7977, Ribavirin, Open Label, Sofosbuvir, Additional relevant MeSH terms:, Hepatitis, Hepatitis, Chronic, Hepatitis C, Hepatitis C, Chronic
Brief summary
This study is to to evaluate the safety, tolerability, and efficacy of sofosbuvir (SOF) plus ribavirin (RBV) in Egyptian adults with genotype 4 hepatitis C virus (HCV) infection.
Interventions
DRUGSOF
Sofosbuvir (SOF) 400 mg tablet administered orally once daily
DRUGRBV
Ribavirin (RBV) 200 mg tablets administered orally in a divided daily dose (\< 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
* Treatment experienced and naïve subjects * Chronic genotype 4 HCV-infection * Not co-infected with HIV * Screening laboratory values within defined thresholds * Use of highly effective contraception methods * Subject 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 subject 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. |
| Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | Up to 24 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 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 24 | Virologic relapse was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit. |
Countries
Egypt
Participant flow
Recruitment details
Participants were enrolled at a total of 3 study sites in Egypt. The first participant was screened on 30 March 2013. The last study visit occurred on 04 August 2014.
Pre-assignment details
141 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| SOF+RBV 12 Weeks, TN SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks (treatment naive (TN)) | 25 |
| SOF+RBV 12 Weeks, TE SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 12 weeks (treatment experienced (TE)) | 27 |
| SOF+RBV 24 Weeks, TN SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (treatment naive) | 24 |
| SOF+RBV 24 Weeks, TE SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks (treatment experienced) | 27 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 12 | 4 |
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | SOF+RBV 12 Weeks, TE | SOF+RBV 24 Weeks, TN | SOF+RBV 12 Weeks, TN | SOF+RBV 24 Weeks, TE | Total |
|---|---|---|---|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 11.5 | 46 years STANDARD_DEVIATION 14.5 | 43 years STANDARD_DEVIATION 12.3 | 51 years STANDARD_DEVIATION 8.3 | 47 years STANDARD_DEVIATION 11.9 |
| Cirrhosis Status No | 22 participants | 21 participants | 22 participants | 21 participants | 86 participants |
| Cirrhosis Status Yes | 5 participants | 3 participants | 3 participants | 6 participants | 17 participants |
| HCV RNA | 5.9 log10 IU/mL STANDARD_DEVIATION 0.57 | 5.5 log10 IU/mL STANDARD_DEVIATION 0.75 | 5.6 log10 IU/mL STANDARD_DEVIATION 0.73 | 6.2 log10 IU/mL STANDARD_DEVIATION 0.49 | 5.8 log10 IU/mL STANDARD_DEVIATION 0.7 |
| HCV RNA Category < 800,000 IU/mL | 11 participants | 15 participants | 15 participants | 8 participants | 49 participants |
| HCV RNA Category ≥ 800,000 IU/mL | 16 participants | 9 participants | 10 participants | 19 participants | 54 participants |
| IL28b Status CC | 1 participants | 6 participants | 8 participants | 5 participants | 20 participants |
| IL28b Status CT | 18 participants | 12 participants | 12 participants | 21 participants | 63 participants |
| IL28b Status TT | 8 participants | 6 participants | 5 participants | 1 participants | 20 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 27 participants | 24 participants | 25 participants | 27 participants | 103 participants |
| Race/Ethnicity, Customized White | 27 participants | 24 participants | 25 participants | 27 participants | 103 participants |
| Sex: Female, Male Female | 8 Participants | 11 Participants | 7 Participants | 8 Participants | 34 Participants |
| Sex: Female, Male Male | 19 Participants | 13 Participants | 18 Participants | 19 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 34 / 52 | 38 / 51 |
| serious Total, serious adverse events | 0 / 52 | 2 / 51 |
Outcome results
Primary
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
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 Weeks, TN | Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | 0 percentage of participants |
| SOF+RBV 12 Weeks, TE | Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | 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 4 HCV infection who were randomized and received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV 12 Weeks, TN | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 84.0 percentage of participants |
| SOF+RBV 12 Weeks, TE | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 70.4 percentage of participants |
| SOF+RBV 24 Weeks, TN | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 91.7 percentage of participants |
| SOF+RBV 24 Weeks, TE | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 88.9 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 12 Weeks, TN | Percentage of Participants Experiencing On-treatment Virologic Failure | 0 percentage of participants |
| SOF+RBV 12 Weeks, TE | Percentage of Participants Experiencing On-treatment Virologic Failure | 0 percentage of participants |
| SOF+RBV 24 Weeks, TN | Percentage of Participants Experiencing On-treatment Virologic Failure | 0 percentage of participants |
| SOF+RBV 24 Weeks, TE | 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 24
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV 12 Weeks, TN | Percentage of Participants Experiencing Virologic Relapse | 16.0 percentage of participants |
| SOF+RBV 12 Weeks, TE | Percentage of Participants Experiencing Virologic Relapse | 29.6 percentage of participants |
| SOF+RBV 24 Weeks, TN | Percentage of Participants Experiencing Virologic Relapse | 4.2 percentage of participants |
| SOF+RBV 24 Weeks, TE | Percentage of Participants Experiencing Virologic Relapse | 11.1 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 12 Weeks, TN | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 88.0 percentage of participants |
| SOF+RBV 12 Weeks, TN | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 84.0 percentage of participants |
| SOF+RBV 12 Weeks, TE | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 70.4 percentage of participants |
| SOF+RBV 12 Weeks, TE | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 74.1 percentage of participants |
| SOF+RBV 24 Weeks, TN | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 91.7 percentage of participants |
| SOF+RBV 24 Weeks, TN | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 91.7 percentage of participants |
| SOF+RBV 24 Weeks, TE | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 88.9 percentage of participants |
| SOF+RBV 24 Weeks, TE | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 88.9 percentage of participants |