Hepatitis C Virus Infection
Conditions
Brief summary
The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of treatment with sofosbuvir (SOF)/velpatasvir (VEL; GS-5816) fixed-dose combination (FDC) for 12 weeks in participants with chronic hepatitis C virus (HCV) infection.
Interventions
DRUGSOF/VEL
SOF/VEL (400/100 mg) FDC 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 * HCV RNA ≥ 10\^4 IU/mL at screening * Chronic HCV infection (≥ 6 months) documented by prior medical history or liver biopsy * Any HCV genotype (1, 2, 3, 4, 5, 6 or indeterminate) * HCV treatment-naive or treatment-experienced * Liver imaging within 6 months of Day 1 is required in cirrhotic patients only to exclude hepatocellular carcinoma (HCC) Key
Exclusion criteria
* Current or prior history of clinically-significant illness (other than HCV), gastrointestinal disorder, clinical hepatic decompensation, or post-operative condition that could interfere with the absorption of the study drug * Pregnant or nursing female or male with pregnant female partner * Chronic liver disease of a non HCV etiology * 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; 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 HCV RNA < LLOQ On Treatment | Weeks 1, 2, 4, 6, 8, 10, and 12 | — |
| Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) | Posttreatment Week 4 | SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping study treatment. |
| Percentage of Participants With Overall Virologic Failure | Up to Posttreatment Week 24 | Virologic failure was defined as: (1) 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 (2) Virologic relapse: confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit. |
| Change From Baseline in HCV RNA | Baseline and up to Week 12 | — |
| Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) | Posttreatment Week 24 | SVR 24 was defined as HCV RNA \< LLOQ at 24 weeks after stopping study treatment. |
Countries
China, Malaysia, Singapore, Thailand, Vietnam
Participant flow
Recruitment details
Participants were enrolled at study sites in Asia. The first participant was screened on 19 April 2016. The last study visit occurred on 27 March 2018.
Pre-assignment details
437 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| SOF/VEL SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks. | 375 |
| Total | 375 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 12 |
| Overall Study | Lost to Follow-up | 2 |
Baseline characteristics
| Characteristic | SOF/VEL |
|---|---|
| Age, Continuous | 45 Years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 374 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| HCV genotype Genotype 1 | 129 Participants |
| HCV genotype Genotype 2 | 64 Participants |
| HCV genotype Genotype 3 | 84 Participants |
| HCV genotype Genotype 6 | 98 Participants |
| HCV RNA Category < 800,000 IU/mL | 116 Participants |
| HCV RNA Category ≥ 800,000 IU/mL | 259 Participants |
| HCV RNA (log10 international units per milliliter [IU/mL]) | 6.2 log10 IU/mL STANDARD_DEVIATION 0.86 |
| IL28b Status CC | 320 Participants |
| IL28b Status CT | 53 Participants |
| IL28b Status TT | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 375 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment China | 264 Participants |
| Region of Enrollment Malaysia | 12 Participants |
| Region of Enrollment Singapore | 22 Participants |
| Region of Enrollment Thailand | 41 Participants |
| Region of Enrollment Vietnam | 36 Participants |
| Sex: Female, Male Female | 178 Participants |
| Sex: Female, Male Male | 197 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 375 |
| other Total, other adverse events | 36 / 375 |
| serious Total, serious adverse events | 3 / 375 |
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 (Overall) | 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 included participants who were enrolled into the study and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL (Overall) | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 96.5 Percentage of participants |
| SOF/VEL (China - Region 1) | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 96.2 Percentage of participants |
| SOF/VEL (Southeast Asia - Region 2) | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 97.3 Percentage of participants |
Comparison: A sample size of 260 participants in Region 1 would provide more than 80% power to detect an improvement of at least 6 percentage points in SVR12 rate from the performance goal of 85% by using a two-sided exact one-sample binomial test at the significance level of 0.05.p-value: <0.0012-sided 1 sample exact binomial test
Secondary
Change From Baseline in HCV RNA
Time frame: Baseline and up to Week 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOF/VEL (Overall) | Change From Baseline in HCV RNA | Change at Week 1 | -4.38 log10 IU/mL | Standard Deviation 0.705 |
| SOF/VEL (Overall) | Change From Baseline in HCV RNA | Change at Week 2 | -4.89 log10 IU/mL | Standard Deviation 0.822 |
| SOF/VEL (Overall) | Change From Baseline in HCV RNA | Change at Week 4 | -5.02 log10 IU/mL | Standard Deviation 0.849 |
| SOF/VEL (Overall) | Change From Baseline in HCV RNA | Change at Week 6 | -5.03 log10 IU/mL | Standard Deviation 0.857 |
| SOF/VEL (Overall) | Change From Baseline in HCV RNA | Change at Week 8 | -5.03 log10 IU/mL | Standard Deviation 0.857 |
| SOF/VEL (Overall) | Change From Baseline in HCV RNA | Change at Week 10 | -5.03 log10 IU/mL | Standard Deviation 0.857 |
| SOF/VEL (Overall) | Change From Baseline in HCV RNA | Change at Week 12 | -5.03 log10 IU/mL | Standard Deviation 0.857 |
Secondary
Percentage of Participants With HCV RNA < LLOQ On Treatment
Time frame: 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 (NUMBER) |
|---|---|---|---|
| SOF/VEL (Overall) | Percentage of Participants With HCV RNA < LLOQ On Treatment | Week 1 | 27.7 Percentage of participants |
| SOF/VEL (Overall) | Percentage of Participants With HCV RNA < LLOQ On Treatment | Week 2 | 73.8 Percentage of participants |
| SOF/VEL (Overall) | Percentage of Participants With HCV RNA < LLOQ On Treatment | Week 4 | 95.5 Percentage of participants |
| SOF/VEL (Overall) | Percentage of Participants With HCV RNA < LLOQ On Treatment | Week 6 | 99.7 Percentage of participants |
| SOF/VEL (Overall) | Percentage of Participants With HCV RNA < LLOQ On Treatment | Week 8 | 100.0 Percentage of participants |
| SOF/VEL (Overall) | Percentage of Participants With HCV RNA < LLOQ On Treatment | Week 10 | 100.0 Percentage of participants |
| SOF/VEL (Overall) | Percentage of Participants With HCV RNA < LLOQ On Treatment | Week 12 | 100.0 Percentage of participants |
Secondary
Percentage of Participants With Overall Virologic Failure
Virologic failure was defined as: (1) 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 (2) 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 (Overall) | Percentage of Participants With Overall Virologic Failure | 3.2 percentage of participants |
Secondary
Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)
SVR 24 was defined as HCV RNA \< LLOQ at 24 weeks after stopping study treatment.
Time frame: Posttreatment Week 24
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL (Overall) | Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) | 96.5 percentage of participants |
Secondary
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)
SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping study treatment.
Time frame: Posttreatment Week 4
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL (Overall) | Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) | 97.1 Percentage of participants |