Hepatitis C Virus Infection
Conditions
Keywords
Chronic
Brief summary
The primary objective of this study is to evaluate the efficacy, safety, and tolerability of treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose combination (FDC) for 8 weeks and of treatment with sofosbuvir/velpatasvir (SOF/VEL) FDC for 12 weeks in participants naive to direct-acting antivirals (DAA) with chronic genotype 3 hepatitis C virus (HCV) infection and cirrhosis.
Interventions
DRUGSOF/VEL/VOX
400/100/100 mg FDC tablet administered orally once daily with food
DRUGSOF/VEL
400/100 mg FDC tablet administered orally once daily without regard to food
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
Key Inclusion Criteria: * Willing and able to provide written informed consent * HCV RNA ≥ 10\^4 IU/mL at screening * Chronic genotype 3 HCV infection (≥ 6 months) * Presence of cirrhosis * HCV treatment naive or treatment experienced with an interferon (IFN)-based regimen * Use of protocol specified methods of contraception Key
Exclusion criteria
* Current or prior history of clinically significant illness that may interfere with participation in the study * Screening ECG with clinically significant abnormalities * Laboratory parameters outside the acceptable range at screening * Pregnant or nursing female * Chronic liver disease not caused by HCV * Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) Note: Other protocol defined Inclusion/
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) at 12 weeks after stopping study treatment. |
| Percentage of Participants Who Permanently Discontinue 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 SVR24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively. |
| Percentage of Participants With HCV RNA < LLOQ On Treatment | Weeks 1, 2, 4, 8 and 12 | — |
| Change From Baseline in HCV RNA | Weeks 1, 2, 4, 8 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), or * Virologic relapse: * Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit |
Countries
Australia, Canada, France, Germany, New Zealand, Puerto Rico, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in North America, Europe, and Asia Pacific. The first participant was screened on 23 December 2015. The last study visit occurred on 02 January 2017.
Pre-assignment details
315 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| SOF/VEL/VOX 8 Weeks SOF/VEL/VOX (400/100/100 mg) tablet orally once daily with food for 8 weeks | 110 |
| SOF/VEL 12 Weeks SOF/VEL (400/100 mg) tablet orally once daily without regard to food for 12 weeks | 109 |
| Total | 219 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Randomized but Not Treated | 0 | 1 |
| Overall Study | Withdrew Consent | 1 | 2 |
Baseline characteristics
| Characteristic | SOF/VEL/VOX 8 Weeks | Total | SOF/VEL 12 Weeks |
|---|---|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 8.5 | 55 years STANDARD_DEVIATION 8.4 | 55 years STANDARD_DEVIATION 8.4 |
| HCV RNA | 6.0 log10 IU/mL STANDARD_DEVIATION 0.8 | 6.2 log10 IU/mL STANDARD_DEVIATION 0.73 | 6.3 log10 IU/mL STANDARD_DEVIATION 0.63 |
| HCV RNA Category < 800,000 IU/mL | 40 Participants | 68 Participants | 28 Participants |
| HCV RNA Category ≥ 800,000 IU/mL | 70 Participants | 151 Participants | 81 Participants |
| IL28b Status CC | 41 Participants | 93 Participants | 52 Participants |
| IL28b Status CT | 57 Participants | 101 Participants | 44 Participants |
| IL28b Status TT | 12 Participants | 25 Participants | 13 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants | 17 Participants | 9 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 9 Participants | 17 Participants | 8 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 101 Participants | 202 Participants | 101 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 100 Participants | 197 Participants | 97 Participants |
| Region of Enrollment Australia | 10 Participants | 26 Participants | 16 Participants |
| Region of Enrollment Canada | 16 Participants | 34 Participants | 18 Participants |
| Region of Enrollment France | 15 Participants | 25 Participants | 10 Participants |
| Region of Enrollment Germany | 9 Participants | 18 Participants | 9 Participants |
| Region of Enrollment New Zealand | 3 Participants | 5 Participants | 2 Participants |
| Region of Enrollment United Kingdom | 7 Participants | 15 Participants | 8 Participants |
| Region of Enrollment United States | 50 Participants | 96 Participants | 46 Participants |
| Sex: Female, Male Female | 36 Participants | 62 Participants | 26 Participants |
| Sex: Female, Male Male | 74 Participants | 157 Participants | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 68 / 110 | 61 / 109 |
| serious Total, serious adverse events | 2 / 110 | 3 / 109 |
Outcome results
Primary
Percentage of Participants Who Permanently Discontinue Study Drug Due to an Adverse Event
Time frame: Up to 12 weeks
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL/VOX 8 Weeks | Percentage of Participants Who Permanently Discontinue Study Drug Due to an Adverse Event | 0 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants Who Permanently Discontinue Study Drug Due to an Adverse Event | 0.9 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) at 12 weeks after stopping study treatment.
Time frame: Posttreatment Week 12
Population: Full Analysis Set: all randomized/enrolled participants who took at least 1 dose of the study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL/VOX 8 Weeks | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 96.4 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 96.3 percentage of participants |
p-value: <0.001Binomial Test
p-value: <0.0012-sided exact 1-sample binomial test
Secondary
Change From Baseline in HCV RNA
Time frame: Weeks 1, 2, 4, 8 and 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOF/VEL/VOX 8 Weeks | Change From Baseline in HCV RNA | Week 1 | -4.06 log10 IU/mL | Standard Deviation 0.716 |
| SOF/VEL/VOX 8 Weeks | Change From Baseline in HCV RNA | Week 2 | -4.60 log10 IU/mL | Standard Deviation 0.825 |
| SOF/VEL/VOX 8 Weeks | Change From Baseline in HCV RNA | Week 4 | -4.84 log10 IU/mL | Standard Deviation 0.789 |
| SOF/VEL/VOX 8 Weeks | Change From Baseline in HCV RNA | Week 8 | -4.90 log10 IU/mL | Standard Deviation 0.801 |
| SOF/VEL 12 Weeks | Change From Baseline in HCV RNA | Week 8 | -5.09 log10 IU/mL | Standard Deviation 0.832 |
| SOF/VEL 12 Weeks | Change From Baseline in HCV RNA | Week 4 | -5.00 log10 IU/mL | Standard Deviation 0.781 |
| SOF/VEL 12 Weeks | Change From Baseline in HCV RNA | Week 1 | -4.09 log10 IU/mL | Standard Deviation 0.653 |
| SOF/VEL 12 Weeks | Change From Baseline in HCV RNA | Week 12 | -5.14 log10 IU/mL | Standard Deviation 0.63 |
| SOF/VEL 12 Weeks | Change From Baseline in HCV RNA | Week 2 | -4.73 log10 IU/mL | Standard Deviation 0.783 |
Secondary
Percentage of Participants With HCV RNA < LLOQ On Treatment
Time frame: Weeks 1, 2, 4, 8 and 12
Population: Percentage of participants in Full Analysis Set with on-treatment data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF/VEL/VOX 8 Weeks | Percentage of Participants With HCV RNA < LLOQ On Treatment | Week 1 | 17.3 percentage of participants |
| SOF/VEL/VOX 8 Weeks | Percentage of Participants With HCV RNA < LLOQ On Treatment | Week 2 | 56.4 percentage of participants |
| SOF/VEL/VOX 8 Weeks | Percentage of Participants With HCV RNA < LLOQ On Treatment | Week 4 | 87.3 percentage of participants |
| SOF/VEL/VOX 8 Weeks | Percentage of Participants With HCV RNA < LLOQ On Treatment | Week 8 | 97.3 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ On Treatment | Week 8 | 99.1 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ On Treatment | Week 4 | 85.2 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ On Treatment | Week 1 | 10.1 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ On Treatment | Week 12 | 100.0 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ On Treatment | Week 2 | 50.9 percentage of participants |
Secondary
Percentage of Participants With SVR 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 after stopping study treatment, respectively.
Time frame: Posttreatment Weeks 4 and 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF/VEL/VOX 8 Weeks | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 97.3 percentage of participants |
| SOF/VEL/VOX 8 Weeks | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 96.4 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 97.2 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 96.3 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), or * 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/VOX 8 Weeks | Percentage of Participants With Virologic Failure | 1.8 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With Virologic Failure | 1.8 percentage of participants |