Chronic Hepatitis C
Conditions
Brief summary
The primary objectives of this study are to evaluate safety, efficacy, and tolerability of treatment with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks in adults on dialysis for end stage renal disease (ESRD) with chronic hepatitis C virus (HCV) infection of any genotype.
Interventions
DRUGSOF/VEL
400/100 mg fixed-dose combination (FDC) tablet(s) 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: * Chronic HCV infected, male and non-pregnant/non-lactating females aged 18 years or older who are on dialysis for ESRD, including adults with HIV co-infection if they are suppressed on a stable, protocol-approved antiretroviral (ARV) regimen for ≥8 weeks prior to screening. NOTE: Other protocol defined Inclusion/
Exclusion criteria
may apply.
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; ie, 15 IU/mL) 12 weeks after stopping the study treatment. |
| Percentage of Participants Who Permanently Discontinued the Study Drug Due to an Adverse Event | First dose date up to Week 12 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HCV RNA | Baseline; Weeks 2, 4, 6, 8, and 12 | — |
| Percentage of Participants With HCV RNA < LLOQ on Treatment | Weeks 2, 4, 6, 8, and 12 | — |
| Percentage of Participants With Virologic Failure | Baseline 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 |
| Number of Participants Who Develop Viral Resistance (as Assessed by Presence of HCV NS5A and NS5B Genes) to SOF and VEL During Treatment and After Discontinuation of Treatment | First dose date up to Posttreatment Week 24 | Baseline deep sequencing of the HCV NS5A and NS5B genes was performed for all participants. For all participants with virologic failure, deep sequencing was performed at the first time point after virologic failure if the plasma or serum sample was available and HCV RNA was \> 1000 IU/mL. |
| Pharmacokinetic (PK) Parameter: AUCtau of SOF | Sparse PK samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) | AUCtau is defined as the population PK derived area under the concentration versus time curve of the drug over the dosing interval. |
| Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4) | Posttreatment Week 4 | SVR4 was defined as HCV RNA \< LLOQ 4 weeks after stopping study treatment. |
| PK Parameter: AUCtau of VEL | Sparse PK samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) | AUCtau is defined as the population PK derived area under the concentration verses time curve of the drug over the dosing interval. |
| PK Parameter: Cmax of SOF | Sparse PK samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) | Cmax is defined as the population PK derived maximum concentration of the drug. |
| PK Parameter: Cmax of GS-331007 (Metabolite of SOF) | Sparse PK samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) | Cmax is defined as the population PK derived maximum concentration of the drug. |
| PK Parameter: Cmax of VEL | Sparse PK samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) | Cmax is defined as the population PK derived maximum concentration of the drug. |
| PK Parameter: Ctau of VEL | Sparse PK samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) | Ctau is defined as the population PK derived concentration of the drug at the end of a 24 hour dosing interval. The 24 hour Ctau is estimated based on the combination of sparse PK samples collected at random times across the dosing interval as well as intensive PK samples collected for up to 12 hours post-dose. |
| PK Parameter: AUCtau of GS-331007 (Metabolite of SOF) | Sparse PK samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) | AUCtau is defined as the population PK derived area under the concentration versus time curve of the drug over the dosing interval. |
| Percentage of Participants With Sustained Virologic Response 24 Weeks After Discontinuation of Therapy (SVR24) | Posttreatment Week 24 | SVR24 was defined as HCV RNA \< LLOQ 24 weeks after stopping study treatment. |
Countries
Australia, Canada, Israel, New Zealand, Spain, United Kingdom
Participant flow
Recruitment details
Participants were enrolled at study sites in Canada, the United Kingdom, Spain, Israel, New Zealand, and Australia. The first participant was screened on 22 March 2017. The last study visit occurred on 07 November 2018.
Pre-assignment details
78 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| SOF/VEL (GT-1) SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with genotype 1 (GT-1) HCV infection | 25 |
| SOF/VEL (GT-2) SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with genotype 2 (GT-2) HCV infection | 7 |
| SOF/VEL (GT-3) SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with genotype 3 (GT-3) HCV infection | 16 |
| SOF/VEL (GT-4) SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with genotype 4 (GT-4) HCV infection | 4 |
| SOF/VEL (GT-6) SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with genotype 6 (GT-6) HCV infection | 2 |
| SOF/VEL (Indeterminate) SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with indeterminate genotype HCV infection | 5 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 2 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | SOF/VEL (GT-1) | SOF/VEL (GT-2) | SOF/VEL (GT-3) | SOF/VEL (GT-4) | SOF/VEL (GT-6) | SOF/VEL (Indeterminate) | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 63 years STANDARD_DEVIATION 11.9 | 67 years STANDARD_DEVIATION 13.5 | 55 years STANDARD_DEVIATION 8.4 | 58 years STANDARD_DEVIATION 15.5 | 69 years STANDARD_DEVIATION 3.5 | 52 years STANDARD_DEVIATION 13 | 60 years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 7 Participants | 16 Participants | 4 Participants | 2 Participants | 4 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| HCV RNA | 6.0 log10 IU/mL STANDARD_DEVIATION 0.7 | 5.2 log10 IU/mL STANDARD_DEVIATION 1.04 | 6.4 log10 IU/mL STANDARD_DEVIATION 0.55 | 5.6 log10 IU/mL STANDARD_DEVIATION 1.55 | 6.4 log10 IU/mL STANDARD_DEVIATION 0.27 | 4.4 log10 IU/mL STANDARD_DEVIATION 1.69 | 5.8 log10 IU/mL STANDARD_DEVIATION 1.02 |
| HCV RNA Category < 800,000 IU/mL | 12 Participants | 5 Participants | 4 Participants | 2 Participants | 0 Participants | 3 Participants | 26 Participants |
| HCV RNA Category ≥ 800,000 IU/mL | 13 Participants | 2 Participants | 12 Participants | 2 Participants | 2 Participants | 2 Participants | 33 Participants |
| IL28b Status CC | 9 Participants | 4 Participants | 6 Participants | 0 Participants | 1 Participants | 3 Participants | 23 Participants |
| IL28b Status CT | 14 Participants | 1 Participants | 8 Participants | 4 Participants | 1 Participants | 2 Participants | 30 Participants |
| IL28b Status TT | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 1 Participants | 7 Participants | 1 Participants | 2 Participants | 1 Participants | 18 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 4 Participants | 7 Participants | 1 Participants | 0 Participants | 3 Participants | 31 Participants |
| Sex: Female, Male Female | 10 Participants | 4 Participants | 5 Participants | 1 Participants | 1 Participants | 3 Participants | 24 Participants |
| Sex: Female, Male Male | 15 Participants | 3 Participants | 11 Participants | 3 Participants | 1 Participants | 2 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 59 |
| other Total, other adverse events | 33 / 59 |
| serious Total, serious adverse events | 11 / 59 |
Outcome results
Primary
Percentage of Participants Who Permanently Discontinued the Study Drug Due to an Adverse Event
Time frame: First dose date up to Week 12
Population: The Safety Analysis Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL (Total) | Percentage of Participants Who Permanently Discontinued the Study Drug Due to an Adverse Event | 0 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; ie, 15 IU/mL) 12 weeks after stopping the study treatment.
Time frame: Posttreatment Week 12
Population: The Full Analysis Set included participants who are enrolled into the study and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL (Total) | Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | 94.9 percentage of participants |
| SOF/VEL (GT-1) | Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | 92.0 percentage of participants |
| SOF/VEL (GT-2) | Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 percentage of participants |
| SOF/VEL (GT-3) | Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | 93.8 percentage of participants |
| SOF/VEL (GT-4) | Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 percentage of participants |
| SOF/VEL (GT-6) | Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 percentage of participants |
| SOF/VEL (Indeterminate) | Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 percentage of participants |
Secondary
Change From Baseline in HCV RNA
Time frame: Baseline; Weeks 2, 4, 6, 8, and 12
Population: Participants in the Full Analysis Set with available date were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOF/VEL (Total) | Change From Baseline in HCV RNA | Change at Week 6 | -4.69 log10 IU/mL | Standard Deviation 1.02 |
| SOF/VEL (Total) | Change From Baseline in HCV RNA | Change at Week 2 | -4.54 log10 IU/mL | Standard Deviation 1.017 |
| SOF/VEL (Total) | Change From Baseline in HCV RNA | Change at Week 12 | -4.69 log10 IU/mL | Standard Deviation 1.02 |
| SOF/VEL (Total) | Change From Baseline in HCV RNA | Change at Week 4 | -4.69 log10 IU/mL | Standard Deviation 1.02 |
| SOF/VEL (Total) | Change From Baseline in HCV RNA | Change at Week 8 | -4.69 log10 IU/mL | Standard Deviation 1.02 |
| SOF/VEL (GT-1) | Change From Baseline in HCV RNA | Change at Week 6 | -4.81 log10 IU/mL | Standard Deviation 0.704 |
| SOF/VEL (GT-1) | Change From Baseline in HCV RNA | Change at Week 4 | -4.81 log10 IU/mL | Standard Deviation 0.704 |
| SOF/VEL (GT-1) | Change From Baseline in HCV RNA | Change at Week 8 | -4.81 log10 IU/mL | Standard Deviation 0.704 |
| SOF/VEL (GT-1) | Change From Baseline in HCV RNA | Change at Week 2 | -4.69 log10 IU/mL | Standard Deviation 0.797 |
| SOF/VEL (GT-1) | Change From Baseline in HCV RNA | Change at Week 12 | -4.81 log10 IU/mL | Standard Deviation 0.704 |
| SOF/VEL (GT-2) | Change From Baseline in HCV RNA | Change at Week 12 | -4.05 log10 IU/mL | Standard Deviation 1.041 |
| SOF/VEL (GT-2) | Change From Baseline in HCV RNA | Change at Week 4 | -4.05 log10 IU/mL | Standard Deviation 1.041 |
| SOF/VEL (GT-2) | Change From Baseline in HCV RNA | Change at Week 2 | -3.78 log10 IU/mL | Standard Deviation 0.84 |
| SOF/VEL (GT-2) | Change From Baseline in HCV RNA | Change at Week 6 | -4.05 log10 IU/mL | Standard Deviation 1.041 |
| SOF/VEL (GT-2) | Change From Baseline in HCV RNA | Change at Week 8 | -4.05 log10 IU/mL | Standard Deviation 1.041 |
| SOF/VEL (GT-3) | Change From Baseline in HCV RNA | Change at Week 6 | -5.20 log10 IU/mL | Standard Deviation 0.551 |
| SOF/VEL (GT-3) | Change From Baseline in HCV RNA | Change at Week 2 | -5.07 log10 IU/mL | Standard Deviation 0.493 |
| SOF/VEL (GT-3) | Change From Baseline in HCV RNA | Change at Week 4 | -5.20 log10 IU/mL | Standard Deviation 0.551 |
| SOF/VEL (GT-3) | Change From Baseline in HCV RNA | Change at Week 8 | -5.20 log10 IU/mL | Standard Deviation 0.551 |
| SOF/VEL (GT-3) | Change From Baseline in HCV RNA | Change at Week 12 | -5.20 log10 IU/mL | Standard Deviation 0.551 |
| SOF/VEL (GT-4) | Change From Baseline in HCV RNA | Change at Week 2 | -4.23 log10 IU/mL | Standard Deviation 1.333 |
| SOF/VEL (GT-4) | Change From Baseline in HCV RNA | Change at Week 12 | -4.48 log10 IU/mL | Standard Deviation 1.547 |
| SOF/VEL (GT-4) | Change From Baseline in HCV RNA | Change at Week 6 | -4.48 log10 IU/mL | Standard Deviation 1.547 |
| SOF/VEL (GT-4) | Change From Baseline in HCV RNA | Change at Week 8 | -4.48 log10 IU/mL | Standard Deviation 1.547 |
| SOF/VEL (GT-4) | Change From Baseline in HCV RNA | Change at Week 4 | -4.48 log10 IU/mL | Standard Deviation 1.547 |
| SOF/VEL (GT-6) | Change From Baseline in HCV RNA | Change at Week 2 | -5.29 log10 IU/mL | Standard Deviation 0.269 |
| SOF/VEL (GT-6) | Change From Baseline in HCV RNA | Change at Week 12 | -5.29 log10 IU/mL | Standard Deviation 0.269 |
| SOF/VEL (GT-6) | Change From Baseline in HCV RNA | Change at Week 8 | -5.29 log10 IU/mL | Standard Deviation 0.269 |
| SOF/VEL (GT-6) | Change From Baseline in HCV RNA | Change at Week 4 | -5.29 log10 IU/mL | Standard Deviation 0.269 |
| SOF/VEL (GT-6) | Change From Baseline in HCV RNA | Change at Week 6 | -5.29 log10 IU/mL | Standard Deviation 0.269 |
| SOF/VEL (Indeterminate) | Change From Baseline in HCV RNA | Change at Week 8 | -3.26 log10 IU/mL | Standard Deviation 1.692 |
| SOF/VEL (Indeterminate) | Change From Baseline in HCV RNA | Change at Week 4 | -3.26 log10 IU/mL | Standard Deviation 1.692 |
| SOF/VEL (Indeterminate) | Change From Baseline in HCV RNA | Change at Week 6 | -3.26 log10 IU/mL | Standard Deviation 1.692 |
| SOF/VEL (Indeterminate) | Change From Baseline in HCV RNA | Change at Week 2 | -3.24 log10 IU/mL | Standard Deviation 1.668 |
| SOF/VEL (Indeterminate) | Change From Baseline in HCV RNA | Change at Week 12 | -3.26 log10 IU/mL | Standard Deviation 1.692 |
Secondary
Number of Participants Who Develop Viral Resistance (as Assessed by Presence of HCV NS5A and NS5B Genes) to SOF and VEL During Treatment and After Discontinuation of Treatment
Baseline deep sequencing of the HCV NS5A and NS5B genes was performed for all participants. For all participants with virologic failure, deep sequencing was performed at the first time point after virologic failure if the plasma or serum sample was available and HCV RNA was \> 1000 IU/mL.
Time frame: First dose date up to Posttreatment Week 24
Population: Participants in the Resistance Analysis Population Set included all participants in the Safety Analysis Set with a virologic outcome and at least 1 gene sequenced. All data are reported at a 15% assay cutoff.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOF/VEL (Total) | Number of Participants Who Develop Viral Resistance (as Assessed by Presence of HCV NS5A and NS5B Genes) to SOF and VEL During Treatment and After Discontinuation of Treatment | 0 Participants |
Secondary
Percentage of Participants With HCV RNA < LLOQ on Treatment
Time frame: Weeks 2, 4, 6, 8, and 12
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF/VEL (Total) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 6 | 100.0 percentage of participants |
| SOF/VEL (Total) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 100.0 percentage of participants |
| SOF/VEL (Total) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 100.0 percentage of participants |
| SOF/VEL (Total) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 12 | 100.0 percentage of participants |
| SOF/VEL (Total) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 67.8 percentage of participants |
| SOF/VEL (GT-1) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 100.0 percentage of participants |
| SOF/VEL (GT-1) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 76.0 percentage of participants |
| SOF/VEL (GT-1) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 6 | 100.0 percentage of participants |
| SOF/VEL (GT-1) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 12 | 100.0 percentage of participants |
| SOF/VEL (GT-1) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 100.0 percentage of participants |
| SOF/VEL (GT-2) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 6 | 100.0 percentage of participants |
| SOF/VEL (GT-2) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 100.0 percentage of participants |
| SOF/VEL (GT-2) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 12 | 100.0 percentage of participants |
| SOF/VEL (GT-2) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 85.7 percentage of participants |
| SOF/VEL (GT-2) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 100.0 percentage of participants |
| SOF/VEL (GT-3) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 100.0 percentage of participants |
| SOF/VEL (GT-3) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 43.8 percentage of participants |
| SOF/VEL (GT-3) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 12 | 100.0 percentage of participants |
| SOF/VEL (GT-3) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 100.0 percentage of participants |
| SOF/VEL (GT-3) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 6 | 100.0 percentage of participants |
| SOF/VEL (GT-4) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 6 | 100.0 percentage of participants |
| SOF/VEL (GT-4) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 100.0 percentage of participants |
| SOF/VEL (GT-4) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 12 | 100.0 percentage of participants |
| SOF/VEL (GT-4) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 50.0 percentage of participants |
| SOF/VEL (GT-4) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 100.0 percentage of participants |
| SOF/VEL (GT-6) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 100.0 percentage of participants |
| SOF/VEL (GT-6) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 100.0 percentage of participants |
| SOF/VEL (GT-6) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 6 | 100.0 percentage of participants |
| SOF/VEL (GT-6) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 100.0 percentage of participants |
| SOF/VEL (GT-6) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 12 | 100.0 percentage of participants |
| SOF/VEL (Indeterminate) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 6 | 100.0 percentage of participants |
| SOF/VEL (Indeterminate) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 80.0 percentage of participants |
| SOF/VEL (Indeterminate) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 100.0 percentage of participants |
| SOF/VEL (Indeterminate) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 12 | 100.0 percentage of participants |
| SOF/VEL (Indeterminate) | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 100.0 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response 24 Weeks After Discontinuation of Therapy (SVR24)
SVR24 was defined as HCV RNA \< LLOQ 24 weeks after stopping study treatment.
Time frame: Posttreatment Week 24
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL (Total) | Percentage of Participants With Sustained Virologic Response 24 Weeks After Discontinuation of Therapy (SVR24) | 94.9 percentage of participants |
| SOF/VEL (GT-1) | Percentage of Participants With Sustained Virologic Response 24 Weeks After Discontinuation of Therapy (SVR24) | 92.0 percentage of participants |
| SOF/VEL (GT-2) | Percentage of Participants With Sustained Virologic Response 24 Weeks After Discontinuation of Therapy (SVR24) | 100.0 percentage of participants |
| SOF/VEL (GT-3) | Percentage of Participants With Sustained Virologic Response 24 Weeks After Discontinuation of Therapy (SVR24) | 93.8 percentage of participants |
| SOF/VEL (GT-4) | Percentage of Participants With Sustained Virologic Response 24 Weeks After Discontinuation of Therapy (SVR24) | 100.0 percentage of participants |
| SOF/VEL (GT-6) | Percentage of Participants With Sustained Virologic Response 24 Weeks After Discontinuation of Therapy (SVR24) | 100.0 percentage of participants |
| SOF/VEL (Indeterminate) | Percentage of Participants With Sustained Virologic Response 24 Weeks After Discontinuation of Therapy (SVR24) | 100.0 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4)
SVR4 was defined as HCV RNA \< LLOQ 4 weeks after stopping study treatment.
Time frame: Posttreatment Week 4
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL (Total) | Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4) | 96.6 percentage of participants |
| SOF/VEL (GT-1) | Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4) | 96.0 percentage of participants |
| SOF/VEL (GT-2) | Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4) | 100.0 percentage of participants |
| SOF/VEL (GT-3) | Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4) | 93.8 percentage of participants |
| SOF/VEL (GT-4) | Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4) | 100.0 percentage of participants |
| SOF/VEL (GT-6) | Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4) | 100.0 percentage of participants |
| SOF/VEL (Indeterminate) | Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4) | 100.0 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: Baseline to Posttreatment Week 24
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL (Total) | Percentage of Participants With Virologic Failure | 3.4 percentage of participants |
| SOF/VEL (GT-1) | Percentage of Participants With Virologic Failure | 4.0 percentage of participants |
| SOF/VEL (GT-2) | Percentage of Participants With Virologic Failure | 0 percentage of participants |
| SOF/VEL (GT-3) | Percentage of Participants With Virologic Failure | 6.3 percentage of participants |
| SOF/VEL (GT-4) | Percentage of Participants With Virologic Failure | 0 percentage of participants |
| SOF/VEL (GT-6) | Percentage of Participants With Virologic Failure | 0 percentage of participants |
| SOF/VEL (Indeterminate) | Percentage of Participants With Virologic Failure | 0 percentage of participants |
Secondary
Pharmacokinetic (PK) Parameter: AUCtau of SOF
AUCtau is defined as the population PK derived area under the concentration versus time curve of the drug over the dosing interval.
Time frame: Sparse PK samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1))
Population: Participants in the PK Analysis Set (all participants who took at least 1 dose of study drug and had at least 1 nonmissing postdose concentration value for the corresponding analyte in plasma) with available data were analyzed. Population PK analyses of all sparse and intensive PK data were utilized to estimate steady-state AUCtau of SOF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOF/VEL (Total) | Pharmacokinetic (PK) Parameter: AUCtau of SOF | 2381.9 h*ng/mL | Standard Deviation 567.63 |
Secondary
PK Parameter: AUCtau of GS-331007 (Metabolite of SOF)
AUCtau is defined as the population PK derived area under the concentration versus time curve of the drug over the dosing interval.
Time frame: Sparse PK samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1))
Population: Participants in the PK analysis Set were analyzed. Population PK analyses of all sparse and intensive PK data were utilized to estimate steady-state AUCtau of GS-331007 .
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOF/VEL (Total) | PK Parameter: AUCtau of GS-331007 (Metabolite of SOF) | 230989.2 h*ng/mL | Standard Deviation 81453.3 |
Secondary
PK Parameter: AUCtau of VEL
AUCtau is defined as the population PK derived area under the concentration verses time curve of the drug over the dosing interval.
Time frame: Sparse PK samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1))
Population: Participants in the PK Analysis Set were analyzed. Population PK analyses of all sparse and intensive PK data were utilized to estimate steady-state AUCtau of VEL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOF/VEL (Total) | PK Parameter: AUCtau of VEL | 4279.4 h*ng/mL | Standard Deviation 2198.77 |
Secondary
PK Parameter: Cmax of GS-331007 (Metabolite of SOF)
Cmax is defined as the population PK derived maximum concentration of the drug.
Time frame: Sparse PK samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1))
Population: Participants in the PK Analysis Set were analyzed. Population PK analyses of all sparse and intensive PK data were utilized to estimate steady-state Cmax of GS-331007.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOF/VEL (Total) | PK Parameter: Cmax of GS-331007 (Metabolite of SOF) | 9776.2 ng/mL | Standard Deviation 3433.16 |
Secondary
PK Parameter: Cmax of SOF
Cmax is defined as the population PK derived maximum concentration of the drug.
Time frame: Sparse PK samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1))
Population: Participants in the PK Analysis set with available data were analyzed. Population PK analyses of all sparse and intensive PK data were utilized to estimate steady-state Cmax of SOF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOF/VEL (Total) | PK Parameter: Cmax of SOF | 1041.0 ng/mL | Standard Deviation 176.96 |
Secondary
PK Parameter: Cmax of VEL
Cmax is defined as the population PK derived maximum concentration of the drug.
Time frame: Sparse PK samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1))
Population: Participants in the PK Analysis Set were analyzed. Population PK analyses of all sparse and intensive PK data were utilized to estimate steady-state Cmax of VEL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOF/VEL (Total) | PK Parameter: Cmax of VEL | 226.9 ng/mL | Standard Deviation 92.8 |
Secondary
PK Parameter: Ctau of VEL
Ctau is defined as the population PK derived concentration of the drug at the end of a 24 hour dosing interval. The 24 hour Ctau is estimated based on the combination of sparse PK samples collected at random times across the dosing interval as well as intensive PK samples collected for up to 12 hours post-dose.
Time frame: Sparse PK samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1))
Population: Participants in the PK Analysis Set were analyzed. Population PK analyses of all sparse and intensive PK data were utilized to estimate steady-state Ctau of VEL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOF/VEL (Total) | PK Parameter: Ctau of VEL | 137.2 ng/mL | Standard Deviation 95.91 |