Hepatitis C
Conditions
Keywords
Chronic Hepatitis C Infection
Brief summary
The primary objectives of this study are to evaluate the safety and efficacy of treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in adults with chronic hepatitis C virus (HCV) infection who have previously received treatment with direct-acting antiviral therapy. Participants randomized to placebo may be eligible for deferred treatment with active SOF/VEL/VOX.
Interventions
DRUGSOF/VEL/VOX
400/100/100 mg fixed dose-combination (FDC) tablet administered orally once daily with food
DRUGPlacebo
Tablet administered orally once daily with food
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
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 HCV infection (≥ 6 months) * Treatment experienced with a direct acting antiviral medication for HCV * 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 results outside of acceptable ranges 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) (Primary Study) | 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 Discontinued Study Drug Due to an Adverse Event (Primary Study) | Up to 12 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HCV RNA (Primary Study) | Baseline; Weeks 1, 2, 4, 8 and 12 | — |
| Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) (Primary Study) | Posttreatment Week 24 | SVR24 was defined as HCV RNA \< LLOQ at 24 weeks after stopping study treatment. |
| Percentage of Participants With Virologic Failure (Primary Study) | Up to Posttreatment Week 24 | Virologic failure is 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. |
| Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) (Primary Study) | Posttreatment Week 4 | SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping study treatment, respectively. |
| Percentage of Participants With HCV RNA < LLOQ On Treatment (Deferred Treatment Substudy) | Weeks 1, 2, 4, 8 and 12 (Deferred Treatment Substudy) | — |
| Change From Baseline in HCV RNA (Deferred Treatment Substudy) | Baseline; Weeks 1, 2, 4, 8, and 12 (Deferred Treatment Substudy) | — |
| Percentage of Participants With Virologic Failure (Deferred Treatment Substudy) | Up to Posttreatment Week 24 (Deferred Treatment Substudy) | Virologic failure is 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. |
| Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (Deferred Treatment Substudy) | Posttreatment Weeks 4, 12, and 24 (Deferred Treatment Substudy) | SVR4, SVR12 and SVR24 was defined as HCV RNA \< LLOQ at 4, 12 and 24 weeks after stopping study treatment, respectively. |
| Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study) | Weeks 1, 2, 4, 8 and 12 | — |
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 11 November 2015. The last study visit occurred on 21 June 2017.
Pre-assignment details
520 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| SOF/VEL/VOX (Primary Study) SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 12 weeks | 263 |
| Placebo (Primary Study) Placebo tablet orally once daily with food for 12 weeks | 152 |
| Total | 415 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Deferred Treatment Substudy | Lost to Follow-up | 0 | 0 | 4 |
| Deferred Treatment Substudy | Withdrew Consent | 0 | 0 | 1 |
| Primary Study | Lost to Follow-up | 4 | 0 | 0 |
| Primary Study | Randomized but Never Treated | 1 | 0 | 0 |
| Primary Study | Withdrew Consent | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | SOF/VEL/VOX (Primary Study) | Total | Placebo (Primary Study) |
|---|---|---|---|
| Age, Continuous | 58 years STANDARD_DEVIATION 8.5 | 58 years STANDARD_DEVIATION 8.5 | 59 years STANDARD_DEVIATION 8 |
| HCV RNA | 6.3 log10 IU/mL STANDARD_DEVIATION 0.68 | 6.3 log10 IU/mL STANDARD_DEVIATION 0.66 | 6.3 log10 IU/mL STANDARD_DEVIATION 0.63 |
| HCV RNA Category < 800,000 IU/mL | 73 Participants | 109 Participants | 36 Participants |
| HCV RNA Category ≥ 800,000 IU/mL | 190 Participants | 306 Participants | 116 Participants |
| IL28b Status CC | 47 Participants | 74 Participants | 27 Participants |
| IL28b Status CT | 165 Participants | 258 Participants | 93 Participants |
| IL28b Status TT | 51 Participants | 83 Participants | 32 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants | 14 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 38 Participants | 60 Participants | 22 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 15 Participants | 25 Participants | 10 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Disclosed | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 247 Participants | 389 Participants | 142 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 211 Participants | 335 Participants | 124 Participants |
| Region of Enrollment Australia | 15 Participants | 26 Participants | 11 Participants |
| Region of Enrollment Canada | 28 Participants | 42 Participants | 14 Participants |
| Region of Enrollment France | 56 Participants | 72 Participants | 16 Participants |
| Region of Enrollment Germany | 16 Participants | 23 Participants | 7 Participants |
| Region of Enrollment New Zealand | 5 Participants | 7 Participants | 2 Participants |
| Region of Enrollment United Kingdom | 8 Participants | 9 Participants | 1 Participants |
| Region of Enrollment United States | 135 Participants | 236 Participants | 101 Participants |
| Sex: Female, Male Female | 63 Participants | 94 Participants | 31 Participants |
| Sex: Female, Male Male | 200 Participants | 321 Participants | 121 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 263 | 0 / 152 | 0 / 147 |
| other Total, other adverse events | 147 / 263 | 80 / 152 | 87 / 147 |
| serious Total, serious adverse events | 5 / 263 | 7 / 152 | 6 / 147 |
Outcome results
Primary
Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event (Primary Study)
Time frame: Up to 12 weeks
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL/VOX (Primary Study) | Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event (Primary Study) | 0.4 percentage of participants |
| Placebo (Primary Study) | Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event (Primary Study) | 2.0 percentage of participants |
Primary
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) (Primary Study)
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: Participants in the Full Analysis Set (all randomized/enrolled participants who took at least 1 dose of study drug) in the SOF/VEL/VOX group were analyzed. This outcome measure was not assessed for participants in the Placebo group because they did not have a Posttreatment Week 12 visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) (Primary Study) | 96.2 percentage of participants |
p-value: <0.0012-sided exact 1-sample binomial test
Secondary
Change From Baseline in HCV RNA (Deferred Treatment Substudy)
Time frame: Baseline; Weeks 1, 2, 4, 8, and 12 (Deferred Treatment Substudy)
Population: Participants with available data in the Full Analysis Set of the Deferred Treatment Substudy were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOF/VEL/VOX (Primary Study) | Change From Baseline in HCV RNA (Deferred Treatment Substudy) | Week 1 | -4.30 log10 IU/mL | Standard Deviation 0.626 |
| SOF/VEL/VOX (Primary Study) | Change From Baseline in HCV RNA (Deferred Treatment Substudy) | Week 2 | -4.93 log10 IU/mL | Standard Deviation 0.602 |
| SOF/VEL/VOX (Primary Study) | Change From Baseline in HCV RNA (Deferred Treatment Substudy) | Week 4 | -5.16 log10 IU/mL | Standard Deviation 0.512 |
| SOF/VEL/VOX (Primary Study) | Change From Baseline in HCV RNA (Deferred Treatment Substudy) | Week 8 | -5.20 log10 IU/mL | Standard Deviation 0.532 |
| SOF/VEL/VOX (Primary Study) | Change From Baseline in HCV RNA (Deferred Treatment Substudy) | Week 12 | -5.20 log10 IU/mL | Standard Deviation 0.532 |
Secondary
Change From Baseline in HCV RNA (Primary Study)
Time frame: Baseline; 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 (Primary Study) | Change From Baseline in HCV RNA (Primary Study) | Week 2 | -4.81 log10 IU/mL | Standard Deviation 0.704 |
| SOF/VEL/VOX (Primary Study) | Change From Baseline in HCV RNA (Primary Study) | Week 8 | -5.11 log10 IU/mL | Standard Deviation 0.678 |
| SOF/VEL/VOX (Primary Study) | Change From Baseline in HCV RNA (Primary Study) | Week 4 | -5.07 log10 IU/mL | Standard Deviation 0.677 |
| SOF/VEL/VOX (Primary Study) | Change From Baseline in HCV RNA (Primary Study) | Week 12 | -5.10 log10 IU/mL | Standard Deviation 0.69 |
| SOF/VEL/VOX (Primary Study) | Change From Baseline in HCV RNA (Primary Study) | Week 1 | -4.20 log10 IU/mL | Standard Deviation 0.733 |
| Placebo (Primary Study) | Change From Baseline in HCV RNA (Primary Study) | Week 12 | 0.03 log10 IU/mL | Standard Deviation 0.43 |
| Placebo (Primary Study) | Change From Baseline in HCV RNA (Primary Study) | Week 1 | 0.02 log10 IU/mL | Standard Deviation 0.3 |
| Placebo (Primary Study) | Change From Baseline in HCV RNA (Primary Study) | Week 2 | 0.02 log10 IU/mL | Standard Deviation 0.322 |
| Placebo (Primary Study) | Change From Baseline in HCV RNA (Primary Study) | Week 4 | -0.01 log10 IU/mL | Standard Deviation 0.441 |
| Placebo (Primary Study) | Change From Baseline in HCV RNA (Primary Study) | Week 8 | 0.05 log10 IU/mL | Standard Deviation 0.434 |
Secondary
Percentage of Participants With HCV RNA < LLOQ On Treatment (Deferred Treatment Substudy)
Time frame: Weeks 1, 2, 4, 8 and 12 (Deferred Treatment Substudy)
Population: Full Analysis Set from the Deferred Treatment Sub study: all enrolled participants who took at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With HCV RNA < LLOQ On Treatment (Deferred Treatment Substudy) | Week 1 | 14.3 percentage of participants |
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With HCV RNA < LLOQ On Treatment (Deferred Treatment Substudy) | Week 2 | 62.6 percentage of participants |
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With HCV RNA < LLOQ On Treatment (Deferred Treatment Substudy) | Week 4 | 93.2 percentage of participants |
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With HCV RNA < LLOQ On Treatment (Deferred Treatment Substudy) | Week 8 | 100.0 percentage of participants |
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With HCV RNA < LLOQ On Treatment (Deferred Treatment Substudy) | Week 12 | 100.0 percentage of participants |
Secondary
Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study)
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 (NUMBER) |
|---|---|---|---|
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study) | Week 4 | 92.7 percentage of participants |
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study) | Week 2 | 56.7 percentage of participants |
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study) | Week 8 | 100.0 percentage of participants |
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study) | Week 12 | 99.6 percentage of participants |
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study) | Week 1 | 15.6 percentage of participants |
| Placebo (Primary Study) | Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study) | Week 12 | 0 percentage of participants |
| Placebo (Primary Study) | Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study) | Week 1 | 0 percentage of participants |
| Placebo (Primary Study) | Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study) | Week 2 | 0 percentage of participants |
| Placebo (Primary Study) | Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study) | Week 4 | 0 percentage of participants |
| Placebo (Primary Study) | Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study) | Week 8 | 0 percentage of participants |
Secondary
Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) (Primary Study)
SVR24 was defined as HCV RNA \< LLOQ at 24 weeks after stopping study treatment.
Time frame: Posttreatment Week 24
Population: Participants in the Full Analysis Set in the SOF/VEL/VOX group were analyzed. This outcome measure was not assessed for participants in the Placebo group because they did not have a Posttreatment Week 24 visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) (Primary Study) | 96.2 percentage of participants |
Secondary
Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (Deferred Treatment Substudy)
SVR4, SVR12 and SVR24 was defined as HCV RNA \< LLOQ at 4, 12 and 24 weeks after stopping study treatment, respectively.
Time frame: Posttreatment Weeks 4, 12, and 24 (Deferred Treatment Substudy)
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (Deferred Treatment Substudy) | SVR4 | 98.6 percentage of participants |
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (Deferred Treatment Substudy) | SVR12 | 97.3 percentage of participants |
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (Deferred Treatment Substudy) | SVR24 | 97.3 percentage of participants |
Secondary
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) (Primary Study)
SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping study treatment, respectively.
Time frame: Posttreatment Week 4
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) (Primary Study) | 97.7 percentage of participants |
| Placebo (Primary Study) | Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) (Primary Study) | 0 percentage of participants |
Secondary
Percentage of Participants With Virologic Failure (Deferred Treatment Substudy)
Virologic failure is 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 (Deferred Treatment Substudy)
Population: Full Analysis Set in the Deferred Treatment Substudy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With Virologic Failure (Deferred Treatment Substudy) | 2.7 percentage of participants |
Secondary
Percentage of Participants With Virologic Failure (Primary Study)
Virologic failure is 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: Participants in the Full Analysis Set in the SOF/VEL/VOX group were analyzed. This outcome measure was not assessed for participants in the Placebo group because they did not have a Posttreatment Week 24 visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL/VOX (Primary Study) | Percentage of Participants With Virologic Failure (Primary Study) | 2.7 percentage of participants |