Hepatitis C Virus Infection
Conditions
Keywords
Hepatitis C, HCV, cirrhosis, Sofosbuvir, Sovaldi, SOF/VEL, GS-5816, GS-7977, liver, Treatment naive, Treatment Experience, genotype 2
Brief summary
The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of treatment with sofosbuvir/velpatasvir (SOF/VEL) fixed-dose combination (FDC) for 12 weeks compared to treatment with sofosbuvir (SOF) plus ribavirin (RBV) for 12 weeks in participants with chronic genotype 2 hepatitis C virus (HCV) infection.
Interventions
DRUGSOF/VEL
SOF/VEL (400/100 mg) FDC tablet administered orally once daily
DRUGSOF
SOF 400 mg 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
* Willing and able to provide written informed consent * HCV RNA ≥ 10\^4 IU/mL * HCV genotype 2 * Chronic HCV infection (≥ 6 months) * Females of childbearing potential must have a negative serum pregnancy test * Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception * Must be of generally good health, with the exception of chronic HCV infection, as determined by the investigator.
Exclusion criteria
* Current or prior history of clinically-significant illness (other than HCV that may interfere with treatment, assessment or compliance with the protocol; * Screening electrocardiogram (ECG) with clinically significant abnormalities * Laboratory results outside of acceptable ranges at Screening * Pregnant or nursing female or male with pregnant female partner * Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, alfa-1 antitrypsin deficiency, cholangitis) * 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) 12 Weeks After Discontinuation of Therapy (SVR12) | Posttreatment Week 12 | SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 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 12 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With SVR 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 after stopping study treatment, respectively. |
| Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 | Weeks 1, 2, 4, 6, 8, 10, and 12 | — |
| Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12 | Baseline; Weeks 1, 2, 4, 6, 8, 10, and 12 | — |
| Percentage of Participants With Virologic Failure | Up to Posttreatment Week 24 | Virologic failure was defined as * On-treatment virologic failure: * 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) * Virologic relapse: * Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States. The first participant was screened on 22 September 2014. The last study visit occurred on 03 September 2015.
Pre-assignment details
317 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| SOF/VEL SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks | 134 |
| SOF+RBV SOF 400 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks | 132 |
| Total | 266 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 0 |
| Overall Study | Lack of Efficacy | 0 | 5 |
| Overall Study | Lost to Follow-up | 4 | 4 |
| Overall Study | Randomized but Never Treated | 1 | 2 |
Baseline characteristics
| Characteristic | SOF+RBV | Total | SOF/VEL |
|---|---|---|---|
| Age, Continuous | 57 years STANDARD_DEVIATION 9.3 | 57 years STANDARD_DEVIATION 10 | 57 years STANDARD_DEVIATION 10.6 |
| Cirrhosis Status Absent | 112 participants | 227 participants | 115 participants |
| Cirrhosis Status Missing | 1 participants | 1 participants | 0 participants |
| Cirrhosis Status Present | 19 participants | 38 participants | 19 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 49 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 107 Participants | 211 Participants | 104 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 4 Participants |
| HCV RNA | 6.4 log10 IU/mL STANDARD_DEVIATION 0.74 | 6.4 log10 IU/mL STANDARD_DEVIATION 0.76 | 6.5 log10 IU/mL STANDARD_DEVIATION 0.78 |
| HCV RNA Category < 800,000 IU/mL | 31 participants | 54 participants | 23 participants |
| HCV RNA Category ≥ 800,000 IU/mL | 101 participants | 212 participants | 111 participants |
| IL28b Status CC | 46 participants | 101 participants | 55 participants |
| IL28b Status CT | 64 participants | 125 participants | 61 participants |
| IL28b Status TT | 22 participants | 40 participants | 18 participants |
| Race/Ethnicity, Customized Asian | 5 participants | 6 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 12 participants | 18 participants | 6 participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Not Disclosed | 1 participants | 3 participants | 2 participants |
| Race/Ethnicity, Customized Other | 2 participants | 3 participants | 1 participants |
| Race/Ethnicity, Customized White | 111 participants | 235 participants | 124 participants |
| Sex: Female, Male Female | 60 Participants | 108 Participants | 48 Participants |
| Sex: Female, Male Male | 72 Participants | 158 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 69 / 134 | 84 / 132 |
| serious Total, serious adverse events | 2 / 134 | 2 / 132 |
Outcome results
Primary
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Time frame: Up to 12 weeks
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL | Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | 0.7 percentage of participants |
| SOF+RBV | 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) 12 Weeks After Discontinuation of Therapy (SVR12)
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Time frame: Posttreatment Week 12
Population: Full Analysis Set: participants randomized or enrolled into the study and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 99.3 percentage of participants |
| SOF+RBV | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 93.9 percentage of participants |
95% CI: [0.2, 10.3]
Comparison: The superiority of SOF/VEL for 12 weeks over SOF+RBV for 12 weeks was to be tested if the efficacy of SOF/VEL for 12 weeks was demonstrated to be statistically noninferior to SOF+RBV for 12 weeks (ie, if the lower bound of the 95% CI for the strata-adjusted difference in the proportions between groups was greater than the prespecified noninferiority margin of -10%).p-value: 0.018Cochran-Mantel-Haenszel
Secondary
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12
Time frame: Baseline; Weeks 1, 2, 4, 6, 8, 10, and 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOF/VEL | Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12 | Change at Wk 4 (SOF/VEL: N= 132; SOF+RBV: N= 131) | -5.29 log10 IU/mL | Standard Deviation 0.781 |
| SOF/VEL | Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12 | Change at Wk 8 (SOF/VEL: N= 133; SOF+RBV: N= 132) | -5.32 log10 IU/mL | Standard Deviation 0.782 |
| SOF/VEL | Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12 | Change at Wk 2 (SOF/VEL: N= 132; SOF+RBV: N= 131) | -5.08 log10 IU/mL | Standard Deviation 0.761 |
| SOF/VEL | Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12 | Change at Wk 10 (SOF/VEL: N= 133; SOF+RBV: N= 132) | -5.32 log10 IU/mL | Standard Deviation 0.782 |
| SOF/VEL | Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12 | Change at Wk 6 (SOF/VEL: N= 133; SOF+RBV: N= 131) | -5.31 log10 IU/mL | Standard Deviation 0.781 |
| SOF/VEL | Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12 | Change at Wk 12 (SOF/VEL: N= 133; SOF+RBV: N= 131) | -5.32 log10 IU/mL | Standard Deviation 0.782 |
| SOF/VEL | Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12 | Change at Wk 1 (SOF/VEL: N= 132; SOF+RBV: N= 131) | -4.51 log10 IU/mL | Standard Deviation 0.666 |
| SOF+RBV | Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12 | Change at Wk 12 (SOF/VEL: N= 133; SOF+RBV: N= 131) | -5.26 log10 IU/mL | Standard Deviation 0.737 |
| SOF+RBV | Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12 | Change at Wk 1 (SOF/VEL: N= 132; SOF+RBV: N= 131) | -4.51 log10 IU/mL | Standard Deviation 0.553 |
| SOF+RBV | Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12 | Change at Wk 2 (SOF/VEL: N= 132; SOF+RBV: N= 131) | -5.04 log10 IU/mL | Standard Deviation 0.701 |
| SOF+RBV | Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12 | Change at Wk 4 (SOF/VEL: N= 132; SOF+RBV: N= 131) | -5.24 log10 IU/mL | Standard Deviation 0.755 |
| SOF+RBV | Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12 | Change at Wk 6 (SOF/VEL: N= 133; SOF+RBV: N= 131) | -5.27 log10 IU/mL | Standard Deviation 0.741 |
| SOF+RBV | Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12 | Change at Wk 8 (SOF/VEL: N= 133; SOF+RBV: N= 132) | -5.27 log10 IU/mL | Standard Deviation 0.739 |
| SOF+RBV | Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12 | Change at Wk 10 (SOF/VEL: N= 133; SOF+RBV: N= 132) | -5.27 log10 IU/mL | Standard Deviation 0.739 |
Secondary
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12
Time frame: Weeks 1, 2, 4, 6, 8, 10, and 12
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF/VEL | Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 | Week 4 (SOF/VEL: N = 133; SOF+RBV: N = 132) | 90.2 percentage of participants |
| SOF/VEL | Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 | Week 8 (SOF/VEL: N = 133; SOF+RBV: N = 132) | 100.0 percentage of participants |
| SOF/VEL | Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 | Week 2 (SOF/VEL: N = 133; SOF+RBV: N = 132) | 57.1 percentage of participants |
| SOF/VEL | Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 | Week 10 (SOF/VEL: N = 133; SOF+RBV: N = 132) | 100.0 percentage of participants |
| SOF/VEL | Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 | Week 6 (SOF/VEL: N = 133; SOF+RBV: N = 132) | 97.7 percentage of participants |
| SOF/VEL | Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 | Week 12 (SOF/VEL: N = 133; SOF+RBV: N = 131) | 100.0 percentage of participants |
| SOF/VEL | Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 | Week 1 (SOF/VEL: N = 133; SOF+RBV: N = 132) | 12.8 percentage of participants |
| SOF+RBV | Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 | Week 12 (SOF/VEL: N = 133; SOF+RBV: N = 131) | 100.0 percentage of participants |
| SOF+RBV | Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 | Week 1 (SOF/VEL: N = 133; SOF+RBV: N = 132) | 22.7 percentage of participants |
| SOF+RBV | Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 | Week 2 (SOF/VEL: N = 133; SOF+RBV: N = 132) | 59.8 percentage of participants |
| SOF+RBV | Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 | Week 4 (SOF/VEL: N = 133; SOF+RBV: N = 132) | 90.2 percentage of participants |
| SOF+RBV | Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 | Week 6 (SOF/VEL: N = 133; SOF+RBV: N = 132) | 99.2 percentage of participants |
| SOF+RBV | Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 | Week 8 (SOF/VEL: N = 133; SOF+RBV: N = 132) | 100.0 percentage of participants |
| SOF+RBV | Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 | Week 10 (SOF/VEL: N = 133; SOF+RBV: N = 132) | 100.0 percentage of participants |
Secondary
Percentage of Participants With SVR 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 after stopping study treatment, respectively.
Time frame: Posttreatment Weeks 4 and 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF/VEL | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 99.3 percentage of participants |
| SOF/VEL | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 99.3 percentage of participants |
| SOF+RBV | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 96.2 percentage of participants |
| SOF+RBV | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 93.9 percentage of participants |
Secondary
Percentage of Participants With Virologic Failure
Virologic failure was defined as * On-treatment virologic failure: * 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) * Virologic relapse: * 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/VEL | Percentage of Participants With Virologic Failure | 0 percentage of participants |
| SOF+RBV | Percentage of Participants With Virologic Failure | 4.5 percentage of participants |