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/velpatasvir (SOF/VEL) for 12 weeks in participants with chronic HCV infection who were coinfected with HIV-1.
Interventions
DRUGSOF/VEL
400/100 mg fixed-dose combination (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: * HCV RNA ≥ 10\^4 IU/mL at screening * HCV genotype 1, 2, 3, 4, 5, 6 * Cirrhosis determination, a fibroscan or liver biopsy may be required * HIV-1 infection * Use of protocol specified method(s) of contraception * Screening laboratory values within defined thresholds Key
Exclusion criteria
* Clinically-significant illness (other than HCV or HIV) or any other major medical disorder that may interfere with individual's treatment, assessment or compliance with the protocol * Current or prior history of clinical hepatic decompensation, hepatocellular carcinoma (HCC) or other malignancy (with the exception of certain resolved skin cancers) * Screening ECG with clinically significant abnormalities * Pregnant or nursing female or male with pregnant female partner * Infection with hepatitis B virus (HBV) * Use of any prohibited concomitant medications as described in the protocol * Chronic use of systemically administered immunosuppressive agents NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | Up to 12 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HCV RNA Change From Baseline/Day 1 | 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 |
| 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. |
| Serum Creatinine Change From Baseline At the End of Treatment and At Posttreatment Week 12 | Week 12; Posttreatment Week 12 | — |
| Percentage of Participants That Maintained HIV-1 RNA < 50 Copies/mL While On HCV Treatment | Up to 12 Weeks | — |
| Percentage of Participants With HCV RNA < LLOQ on Treatment | Up to 12 Weeks | — |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 17 study sites in the United States. The first participant was screened on 01 July 2015. The last study visit occurred on 22 June 2016.
Pre-assignment details
149 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| SOF/VEL 12 Weeks SOF/VEL (400/100 mg) FDC tablet orally once daily in HCV treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic HCV infection who were coinfected with HIV-1 | 106 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Enrolled but Never Treated | 1 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Withdrew Consent | 3 |
Baseline characteristics
| Characteristic | SOF/VEL 12 Weeks |
|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 9 |
| HCV RNA | 6.3 log10 IU/mL STANDARD_DEVIATION 0.57 |
| HCV RNA Category < 800,000 IU/mL | 28 Participants |
| HCV RNA Category ≥ 800,000 IU/mL | 78 Participants |
| HIV RNA category Boosted TDF Containing Regimens HIV RNA < 50 copies/mL | 55 Participants |
| HIV RNA category Boosted TDF Containing Regimens HIV RNA ≥ 50 copies/mL | 1 Participants |
| HIV RNA category Non-Boosted TDF Containing Regimens HIV RNA < 50 copies/mL | 35 Participants |
| HIV RNA category Non-Boosted TDF Containing Regimens HIV RNA ≥ 50 copies/mL | 0 Participants |
| HIV RNA category Non TDF Containing Regimens HIV RNA < 50 copies/mL | 14 Participants |
| HIV RNA category Non TDF Containing Regimens HIV RNA ≥ 50 copies/mL | 1 Participants |
| IL28b Status CC | 24 Participants |
| IL28b Status CT | 52 Participants |
| IL28b Status TT | 30 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 48 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 15 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 91 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 54 Participants |
| Serum Creatinine Boosted TDF Containing Regimens | 1.02 mg/dL STANDARD_DEVIATION 0.194 |
| Serum Creatinine Non-Boosted TDF Containing Regimens | 0.98 mg/dL STANDARD_DEVIATION 1.44 |
| Serum Creatinine Non TDF Containing Regimens | 1.02 mg/dL STANDARD_DEVIATION 0.255 |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 91 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 34 / 56 | 19 / 35 | 9 / 15 |
| serious Total, serious adverse events | 2 / 56 | 0 / 35 | 0 / 15 |
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 | 1.9 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: All enrolled participants who received at least one 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) | 95.3 percentage of participants |
Secondary
HCV RNA Change From Baseline/Day 1
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/Day 1 | Change at Week 1 | -4.47 log10 IU/mL | Standard Deviation 0.606 |
| SOF/VEL 12 Weeks | HCV RNA Change From Baseline/Day 1 | Change at Week 2 | -4.97 log10 IU/mL | Standard Deviation 0.577 |
| SOF/VEL 12 Weeks | HCV RNA Change From Baseline/Day 1 | Change at Week 4 | -5.15 log10 IU/mL | Standard Deviation 0.56 |
| SOF/VEL 12 Weeks | HCV RNA Change From Baseline/Day 1 | Change at Week 6 | -5.18 log10 IU/mL | Standard Deviation 0.572 |
| SOF/VEL 12 Weeks | HCV RNA Change From Baseline/Day 1 | Change at Week 8 | -5.17 log10 IU/mL | Standard Deviation 0.575 |
| SOF/VEL 12 Weeks | HCV RNA Change From Baseline/Day 1 | Change at Week 10 | -5.17 log10 IU/mL | Standard Deviation 0.575 |
| SOF/VEL 12 Weeks | HCV RNA Change From Baseline/Day 1 | Change at Week 12 | -5.17 log10 IU/mL | Standard Deviation 0.575 |
Secondary
Percentage of Participants That Maintained HIV-1 RNA < 50 Copies/mL While On HCV Treatment
Time frame: Up to 12 Weeks
Population: Participants in the Safety Analysis Set with available data were analyzed by TDF-containing ART at baseline:~* Boosted TDF-containing regimens~* Non-boosted TDF-containing regimens~* Non TDF-containing regimens
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF/VEL 12 Weeks | Percentage of Participants That Maintained HIV-1 RNA < 50 Copies/mL While On HCV Treatment | Week 8 | 96.3 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants That Maintained HIV-1 RNA < 50 Copies/mL While On HCV Treatment | Week 4 | 94.4 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants That Maintained HIV-1 RNA < 50 Copies/mL While On HCV Treatment | Week 12 | 96.2 percentage of participants |
| SOF/VEL 12 Weeks (Non-Boosted TDF Containing Regimens) | Percentage of Participants That Maintained HIV-1 RNA < 50 Copies/mL While On HCV Treatment | Week 8 | 97.1 percentage of participants |
| SOF/VEL 12 Weeks (Non-Boosted TDF Containing Regimens) | Percentage of Participants That Maintained HIV-1 RNA < 50 Copies/mL While On HCV Treatment | Week 4 | 97.1 percentage of participants |
| SOF/VEL 12 Weeks (Non-Boosted TDF Containing Regimens) | Percentage of Participants That Maintained HIV-1 RNA < 50 Copies/mL While On HCV Treatment | Week 12 | 100 percentage of participants |
| SOF/VEL 12 Weeks (Non TDF Containing Regimens) | Percentage of Participants That Maintained HIV-1 RNA < 50 Copies/mL While On HCV Treatment | Week 4 | 100 percentage of participants |
| SOF/VEL 12 Weeks (Non TDF Containing Regimens) | Percentage of Participants That Maintained HIV-1 RNA < 50 Copies/mL While On HCV Treatment | Week 12 | 92.9 percentage of participants |
| SOF/VEL 12 Weeks (Non TDF Containing Regimens) | Percentage of Participants That Maintained HIV-1 RNA < 50 Copies/mL While On HCV Treatment | Week 8 | 100 percentage of participants |
Secondary
Percentage of Participants With HCV RNA < LLOQ on Treatment
Time frame: Up to 12 Weeks
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 on Treatment | Week 12 | 100.0 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 1 | 25.7 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 68.0 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 92.2 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 6 | 99.0 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 100.0 percentage of participants |
| SOF/VEL 12 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 10 | 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 | 95.3 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 | 95.3 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 | 1.9 percentage of participants |
Secondary
Serum Creatinine Change From Baseline At the End of Treatment and At Posttreatment Week 12
Time frame: Week 12; Posttreatment Week 12
Population: Participants in the Safety Analysis Set with available data were analyzed by TDF-containing ART at baseline:~* Boosted TDF-containing regimens~* Non-boosted TDF-containing regimens~* Non TDF-containing regimens
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOF/VEL 12 Weeks | Serum Creatinine Change From Baseline At the End of Treatment and At Posttreatment Week 12 | Change at Week 12 | 0.09 mg/dL | Standard Deviation 0.196 |
| SOF/VEL 12 Weeks | Serum Creatinine Change From Baseline At the End of Treatment and At Posttreatment Week 12 | Change at Posttreatment Week 12 | 0.04 mg/dL | Standard Deviation 0.153 |
| SOF/VEL 12 Weeks (Non-Boosted TDF Containing Regimens) | Serum Creatinine Change From Baseline At the End of Treatment and At Posttreatment Week 12 | Change at Week 12 | 0.04 mg/dL | Standard Deviation 0.107 |
| SOF/VEL 12 Weeks (Non-Boosted TDF Containing Regimens) | Serum Creatinine Change From Baseline At the End of Treatment and At Posttreatment Week 12 | Change at Posttreatment Week 12 | 0.02 mg/dL | Standard Deviation 0.142 |
| SOF/VEL 12 Weeks (Non TDF Containing Regimens) | Serum Creatinine Change From Baseline At the End of Treatment and At Posttreatment Week 12 | Change at Week 12 | 0.00 mg/dL | Standard Deviation 0.083 |
| SOF/VEL 12 Weeks (Non TDF Containing Regimens) | Serum Creatinine Change From Baseline At the End of Treatment and At Posttreatment Week 12 | Change at Posttreatment Week 12 | -0.06 mg/dL | Standard Deviation 0.204 |