Hepatitis C Virus Infection
Conditions
Keywords
Sofosbuvir, SOF/GS-5816, GS-5816, Hepatitis C, HCV, Cirrhosis, Velpatasvir
Brief summary
The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of treatment with sofosbuvir/velpatasvir (SOF/VEL) in participants with chronic genotype 1, 2, 4, 6 or indeterminate HCV infection who received placebo in the Gilead-sponsored study GS-US-342-1138.
Interventions
DRUGSOF/VEL
400/100 mg tablet administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
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 * Chronic HCV infection (≥ 6 months) documented by prior medical history or liver biopsy * Was administered placebo to match SOF/VEL in Gilead study GS-US-342-1138 * HCV RNA ≥ 10\^4 IU/mL at screening * Classification as treatment naive or treatment experienced * Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception Key
Exclusion criteria
* Current or prior history of clinically-significant illness (other than HCV) or any other major medical disorder that may interfere with treatment, assessment, or compliance with the protocol; individuals currently under evaluation for a potentially clinically-significant illness (other than HCV) are also excluded. * Screening electrocardiogram (ECG) with clinically significant abnormalities * Laboratory results outside of acceptable ranges at screening * Prior exposure to SOF or other nucleotide analogue HCV NS5B inhibitor or any HCV NS5A inhibitor * 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 Who Permanently Discontinued Any Study Drug Due to an Adverse Event | Up to 12 weeks | — |
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | Posttreatment Week 12 | SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 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 With HCV RNA < LLOQ While on Treatment | Baseline to Week 12 | — |
| HCV RNA Change From Baseline | Baseline to Week 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
Belgium, Canada, France, Germany, Hong Kong, Italy, 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 February 2015. The last study visit occurred on 15 June 2016.
Pre-assignment details
116 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| SOF/VEL 12 Weeks SOF/VEL (400/100 mg) FDC tablet orally once daily | 111 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Withdrew Consent | 3 |
Baseline characteristics
| Characteristic | SOF/VEL 12 Weeks |
|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 10.4 |
| HCV RNA | 6.3 log10 IU/mL STANDARD_DEVIATION 0.55 |
| HCV RNA Category < 800,000 IU/mL | 30 Participants |
| HCV RNA Category ≥ 800,000 IU/mL | 81 Participants |
| IL28b Status CC | 36 Participants |
| IL28b Status CT | 50 Participants |
| IL28b Status TT | 25 Participants |
| Race/Ethnicity, Customized Asian | 11 Participants |
| Race/Ethnicity, Customized Black or African American | 12 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 5 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 106 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized White | 85 Participants |
| Region of Enrollment Belgium | 4 Participants |
| Region of Enrollment Canada | 6 Participants |
| Region of Enrollment China | 1 Participants |
| Region of Enrollment France | 31 Participants |
| Region of Enrollment Germany | 7 Participants |
| Region of Enrollment Hong Kong | 3 Participants |
| Region of Enrollment Italy | 2 Participants |
| Region of Enrollment Puerto Rico | 2 Participants |
| Region of Enrollment United Kingdom | 13 Participants |
| Region of Enrollment United States | 42 Participants |
| Sex: Female, Male Female | 46 Participants |
| Sex: Female, Male Male | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 46 / 111 |
| serious Total, serious adverse events | 5 / 111 |
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 12 Weeks | Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | 0.9 percentage of participants |
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
Time frame: Posttreatment Week 12
Population: Full Analysis Set (FAS) included all enrolled participants who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL 12 Weeks | Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | 97.3 percentage of participants |
Secondary
HCV RNA Change From Baseline
Time frame: Baseline to Week 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOF/VEL 12 Weeks | HCV RNA Change From Baseline | Change at Week 1 | -4.23 log10 IU/mL | Standard Deviation 0.592 |
| SOF/VEL 12 Weeks | HCV RNA Change From Baseline | Change at Week 2 | -4.79 log10 IU/mL | Standard Deviation 0.627 |
| SOF/VEL 12 Weeks | HCV RNA Change From Baseline | Change at Week 4 | -5.10 log10 IU/mL | Standard Deviation 0.546 |
| SOF/VEL 12 Weeks | HCV RNA Change From Baseline | Change at Week 6 | -5.11 log10 IU/mL | Standard Deviation 0.552 |
| SOF/VEL 12 Weeks | HCV RNA Change From Baseline | Change at Week 8 | -5.11 log10 IU/mL | Standard Deviation 0.554 |
| SOF/VEL 12 Weeks | HCV RNA Change From Baseline | Change at Week 10 | -5.11 log10 IU/mL | Standard Deviation 0.554 |
| SOF/VEL 12 Weeks | HCV RNA Change From Baseline | Change at Week 12 | -5.11 log10 IU/mL | Standard Deviation 0.556 |
Secondary
Percentage of Participants With HCV RNA < LLOQ While on Treatment
Time frame: Baseline to Week 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 4 | 94.6 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 1 | 18.0 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 2 | 55.0 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 6 | 99.1 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 8 | 100.0 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 10 | 100.0 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 12 | 100.0 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response 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/VEL 12 Weeks | Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 98.2 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 97.3 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) * 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 12 Weeks | Percentage of Participants With Virologic Failure | 0.9 percentage of participants |