Hepatitis C Virus Infection
Conditions
Brief summary
The primary objectives of this study are to evaluate the safety, efficacy and tolerability of treatment with ledipasvir/sofosbuvir (LDV/SOF) in adults with chronic HCV infection who are on dialysis for ESRD.
Interventions
DRUGLDV/SOF
90/400 mg fixed- dose combination (FDC) tablet administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
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 genotype 1, 2 (Taiwan only), 4, 5, or 6 male and nonpregnant/ nonlactating females aged 18 years or older who are on dialysis for ESRD, including adults with HIV coinfection if they are suppressed on a stable, protocol-approved antiretroviral (ARV) regimens 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 (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | Posttreatment Week 12 | SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment. The exact 95% confidence interval (CI) for the percentage within treatment group was based on the Clopper-Pearson method. |
| Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event | First dose date up to Week 24 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HCV RNA < LLOQ on Treatment | Weeks 2, 4, 6, 8, 12, 16, 20, 24 | The total number of participants with HCV RNA \< LLOQ was the sum of the number of participants with HCV RNA \< LLOQ detected plus the number of participants with HCV RNA \< LLOQ target not detected (TND). LLOQ was 15 IU/mL. The exact 95% CI for the percentage within treatment group was based on the Clopper-Pearson method. |
| HCV RNA | Weeks 2, 4, 6, 8, 12, 16, 20, 24 | — |
| Change From Baseline in HCV RNA | Weeks 2, 4, 6, 8, 12, 16, 20, 24 | — |
| Percentage of Participants With Virologic Failure | Baseline 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 Who Developed Resistance to LDV and SOF | Baseline up to Posttreatment Week 24 | — |
| Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) | Posttreatment Week 4 | SVR4 was defined as HCV RNA \< LLOQ (ie, 15 IU/mL) at 4 weeks after stopping study treatment. The exact 95% CI for the percentage within treatment group was based on the Clopper-Pearson method. |
| 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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) | AUCtau is defined as the population PK derived area under the concentration versus time curve of the drug over the dosing interval. |
| 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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) | AUCtau is defined as the population PK derived area under the concentration versus time curve of the drug over the dosing interval. |
| PK Parameter: Cmax of LDV | 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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) | Cmax is defined as the population PK derived maximum concentration of the drug. |
| 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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) | 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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) | Cmax is defined as the population PK derived maximum concentration of the drug. |
| Pharmacokinetics (PK) Parameter: AUCtau of LDV | 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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) | 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 SVR at 24 Weeks After Discontinuation of Therapy (SVR24) | Posttreatment Week 24 | SVR24 was defined as HCV RNA \< LLOQ (ie, 15 IU/mL) at 24 weeks after stopping study treatment. The exact 95% CI for the percentage within treatment group was based on the Clopper-Pearson method. |
Countries
Belgium, Germany, Italy, Taiwan, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Taiwan, Italy, Germany, the United States, and Belgium. The first participant was screened on 27 June 2017. The last study visit occurred on 14 February 2019.
Pre-assignment details
124 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| LDV/SOF for 8 Weeks Treatment-naive genotype 1 participants without cirrhosis received LDV/SOF (90/400 mg) FDC tablet once daily orally with or without food for 8 weeks. | 45 |
| LDV/SOF for 12 Weeks Treatment-experienced genotype 1 participants and treatment-naive or treatment-experienced genotype 2 (Taiwan only), 4, 5, and 6 participants without cirrhosis received LDV/SOF (90/400 mg) FDC tablet once daily orally with or without food for 12 weeks. | 31 |
| LDV/SOF for 24 Weeks Participants with compensated cirrhosis received LDV/SOF (90/400 mg) FDC tablet once daily orally with or without food for 24 weeks. | 19 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Death | 3 | 0 | 3 |
| Overall Study | Withdrew Consent | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | LDV/SOF for 8 Weeks | LDV/SOF for 24 Weeks | LDV/SOF for 12 Weeks | Total |
|---|---|---|---|---|
| Age, Continuous | 60 years STANDARD_DEVIATION 12 | 65 years STANDARD_DEVIATION 7.1 | 59 years STANDARD_DEVIATION 10.1 | 61 years STANDARD_DEVIATION 10.7 |
| Cirrhosis Status No | 45 Participants | 0 Participants | 31 Participants | 76 Participants |
| Cirrhosis Status Yes | 0 Participants | 19 Participants | 0 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants | 17 Participants | 31 Participants | 93 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| HCV Genotype Genotype 1 | 45 Participants | 15 Participants | 8 Participants | 68 Participants |
| HCV Genotype Genotype 2 | 0 Participants | 2 Participants | 19 Participants | 21 Participants |
| HCV Genotype Genotype 4 | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| HCV Genotype Genotype 5 | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| HCV Genotype Genotype 6 | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| HCV Genotype Indeterminate | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| HCV RNA | 5.8 log10 IU/mL STANDARD_DEVIATION 0.8 | 5.9 log10 IU/mL STANDARD_DEVIATION 0.63 | 5.9 log10 IU/mL STANDARD_DEVIATION 0.95 | 5.8 log10 IU/mL STANDARD_DEVIATION 0.82 |
| HCV RNA Category < 800,000 IU/mL | 24 Participants | 10 Participants | 14 Participants | 48 Participants |
| HCV RNA Category ≥ 800,000 IU/mL | 21 Participants | 9 Participants | 17 Participants | 47 Participants |
| IL28b Status CC | 24 Participants | 9 Participants | 24 Participants | 57 Participants |
| IL28b Status CT | 12 Participants | 9 Participants | 5 Participants | 26 Participants |
| IL28b Status TT | 9 Participants | 1 Participants | 2 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 21 Participants | 11 Participants | 29 Participants | 61 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 6 Participants | 2 Participants | 28 Participants |
| Region of Enrollment Belgium | 3 participants | 0 participants | 0 participants | 3 participants |
| Region of Enrollment Germany | 8 participants | 0 participants | 0 participants | 8 participants |
| Region of Enrollment Italy | 9 participants | 5 participants | 2 participants | 16 participants |
| Region of Enrollment Taiwan | 21 participants | 10 participants | 29 participants | 60 participants |
| Region of Enrollment United States | 4 participants | 4 participants | 0 participants | 8 participants |
| Sex: Female, Male Female | 16 Participants | 4 Participants | 19 Participants | 39 Participants |
| Sex: Female, Male Male | 29 Participants | 15 Participants | 12 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 45 | 0 / 31 | 3 / 19 |
| other Total, other adverse events | 23 / 45 | 28 / 31 | 15 / 19 |
| serious Total, serious adverse events | 4 / 45 | 2 / 31 | 6 / 19 |
Outcome results
Primary
Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event
Time frame: First dose date up to Week 24
Population: The Safety Analysis Set included all participants who received at least 1 dose of study drug. Participants were grouped within the Safety Analysis Set according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF for 8 Weeks | Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event | 0 percentage of participants |
| LDV/SOF for 12 Weeks | Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event | 0 percentage of participants |
| LDV/SOF for 24 Weeks | Percentage of Participants Who Permanently Discontinued 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 hepatitis C virus ribonucleic acid (HCV RNA) \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment. The exact 95% confidence interval (CI) for the percentage within treatment group was based on the Clopper-Pearson method.
Time frame: Posttreatment Week 12
Population: The Full Analysis Set (FAS) included participants who were enrolled into the study and received at least 1 dose of study drug. Participants were grouped within the Full Analysis Set by genotype and treatment group to which they were enrolled.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF for 8 Weeks | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 93.3 percentage of participants |
| LDV/SOF for 12 Weeks | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 percentage of participants |
| LDV/SOF for 24 Weeks | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 84.2 percentage of participants |
Secondary
Change From Baseline in HCV RNA
Time frame: Weeks 2, 4, 6, 8, 12, 16, 20, 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDV/SOF for 8 Weeks | Change From Baseline in HCV RNA | Change at Week 8 | -4.61 log10 IU/mL | Standard Deviation 0.805 |
| LDV/SOF for 8 Weeks | Change From Baseline in HCV RNA | Change at Week 6 | -4.61 log10 IU/mL | Standard Deviation 0.805 |
| LDV/SOF for 8 Weeks | Change From Baseline in HCV RNA | Change at Week 2 | -4.63 log10 IU/mL | Standard Deviation 0.799 |
| LDV/SOF for 8 Weeks | Change From Baseline in HCV RNA | Change at Week 4 | -4.61 log10 IU/mL | Standard Deviation 0.805 |
| LDV/SOF for 12 Weeks | Change From Baseline in HCV RNA | Change at Week 2 | -4.71 log10 IU/mL | Standard Deviation 0.894 |
| LDV/SOF for 12 Weeks | Change From Baseline in HCV RNA | Change at Week 6 | -4.79 log10 IU/mL | Standard Deviation 0.95 |
| LDV/SOF for 12 Weeks | Change From Baseline in HCV RNA | Change at Week 8 | -4.79 log10 IU/mL | Standard Deviation 0.95 |
| LDV/SOF for 12 Weeks | Change From Baseline in HCV RNA | Change at Week 4 | -4.79 log10 IU/mL | Standard Deviation 0.95 |
| LDV/SOF for 12 Weeks | Change From Baseline in HCV RNA | Change at Week 12 | -4.79 log10 IU/mL | Standard Deviation 0.95 |
| LDV/SOF for 24 Weeks | Change From Baseline in HCV RNA | Change at Week 24 | -4.75 log10 IU/mL | Standard Deviation 0.466 |
| LDV/SOF for 24 Weeks | Change From Baseline in HCV RNA | Change at Week 2 | -4.67 log10 IU/mL | Standard Deviation 0.631 |
| LDV/SOF for 24 Weeks | Change From Baseline in HCV RNA | Change at Week 4 | -4.71 log10 IU/mL | Standard Deviation 0.631 |
| LDV/SOF for 24 Weeks | Change From Baseline in HCV RNA | Change at Week 6 | -4.81 log10 IU/mL | Standard Deviation 0.474 |
| LDV/SOF for 24 Weeks | Change From Baseline in HCV RNA | Change at Week 8 | -4.81 log10 IU/mL | Standard Deviation 0.474 |
| LDV/SOF for 24 Weeks | Change From Baseline in HCV RNA | Change at Week 12 | -4.79 log10 IU/mL | Standard Deviation 0.48 |
| LDV/SOF for 24 Weeks | Change From Baseline in HCV RNA | Change at Week 16 | -4.79 log10 IU/mL | Standard Deviation 0.48 |
| LDV/SOF for 24 Weeks | Change From Baseline in HCV RNA | Change at Week 20 | -4.79 log10 IU/mL | Standard Deviation 0.48 |
Secondary
HCV RNA
Time frame: Weeks 2, 4, 6, 8, 12, 16, 20, 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDV/SOF for 8 Weeks | HCV RNA | Week 8 | 1.15 log10 IU/mL | Standard Deviation 0 |
| LDV/SOF for 8 Weeks | HCV RNA | Week 6 | 1.15 log10 IU/mL | Standard Deviation 0 |
| LDV/SOF for 8 Weeks | HCV RNA | Week 2 | 1.17 log10 IU/mL | Standard Deviation 0.107 |
| LDV/SOF for 8 Weeks | HCV RNA | Week 4 | 1.15 log10 IU/mL | Standard Deviation 0 |
| LDV/SOF for 12 Weeks | HCV RNA | Week 2 | 1.22 log10 IU/mL | Standard Deviation 0.261 |
| LDV/SOF for 12 Weeks | HCV RNA | Week 6 | 1.15 log10 IU/mL | Standard Deviation 0 |
| LDV/SOF for 12 Weeks | HCV RNA | Week 8 | 1.15 log10 IU/mL | Standard Deviation 0 |
| LDV/SOF for 12 Weeks | HCV RNA | Week 4 | 1.15 log10 IU/mL | Standard Deviation 0 |
| LDV/SOF for 12 Weeks | HCV RNA | Week 12 | 1.15 log10 IU/mL | Standard Deviation 0 |
| LDV/SOF for 24 Weeks | HCV RNA | Week 24 | 1.15 log10 IU/mL | Standard Deviation 0 |
| LDV/SOF for 24 Weeks | HCV RNA | Week 2 | 1.18 log10 IU/mL | Standard Deviation 0.098 |
| LDV/SOF for 24 Weeks | HCV RNA | Week 4 | 1.15 log10 IU/mL | Standard Deviation 0 |
| LDV/SOF for 24 Weeks | HCV RNA | Week 6 | 1.15 log10 IU/mL | Standard Deviation 0 |
| LDV/SOF for 24 Weeks | HCV RNA | Week 8 | 1.15 log10 IU/mL | Standard Deviation 0 |
| LDV/SOF for 24 Weeks | HCV RNA | Week 12 | 1.15 log10 IU/mL | Standard Deviation 0 |
| LDV/SOF for 24 Weeks | HCV RNA | Week 16 | 1.15 log10 IU/mL | Standard Deviation 0 |
| LDV/SOF for 24 Weeks | HCV RNA | Week 20 | 1.15 log10 IU/mL | Standard Deviation 0 |
Secondary
Percentage of Participants Who Developed Resistance to LDV and SOF
Time frame: Baseline up to Posttreatment Week 24
Population: The Resistance Analysis Population was defined as all participants in the Safety Analysis Set with a virologic outcome and at least 1 gene sequenced. As no participant had a relapse in this study, this outcome could not be analyzed.
Secondary
Percentage of Participants With HCV RNA < LLOQ on Treatment
The total number of participants with HCV RNA \< LLOQ was the sum of the number of participants with HCV RNA \< LLOQ detected plus the number of participants with HCV RNA \< LLOQ target not detected (TND). LLOQ was 15 IU/mL. The exact 95% CI for the percentage within treatment group was based on the Clopper-Pearson method.
Time frame: Weeks 2, 4, 6, 8, 12, 16, 20, 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF for 8 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 100.0 percentage of participants |
| LDV/SOF for 8 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 100.0 percentage of participants |
| LDV/SOF for 8 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 6 | 100.0 percentage of participants |
| LDV/SOF for 8 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 84.4 percentage of participants |
| LDV/SOF for 12 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 90.3 percentage of participants |
| LDV/SOF for 12 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 100.0 percentage of participants |
| LDV/SOF for 12 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 100.0 percentage of participants |
| LDV/SOF for 12 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 6 | 100.0 percentage of participants |
| LDV/SOF for 12 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 12 | 100.0 percentage of participants |
| LDV/SOF for 24 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 24 | 100.0 percentage of participants |
| LDV/SOF for 24 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 84.2 percentage of participants |
| LDV/SOF for 24 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 100.0 percentage of participants |
| LDV/SOF for 24 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 6 | 94.7 percentage of participants |
| LDV/SOF for 24 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 100.0 percentage of participants |
| LDV/SOF for 24 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 12 | 100.0 percentage of participants |
| LDV/SOF for 24 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 16 | 100.0 percentage of participants |
| LDV/SOF for 24 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 20 | 100.0 percentage of participants |
Secondary
Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)
SVR24 was defined as HCV RNA \< LLOQ (ie, 15 IU/mL) at 24 weeks after stopping study treatment. The exact 95% CI for the percentage within treatment group was based on the Clopper-Pearson method.
Time frame: Posttreatment Week 24
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF for 8 Weeks | Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) | 93.3 percentage of participants |
| LDV/SOF for 12 Weeks | Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) | 100.0 percentage of participants |
| LDV/SOF for 24 Weeks | Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) | 84.2 percentage of participants |
Secondary
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)
SVR4 was defined as HCV RNA \< LLOQ (ie, 15 IU/mL) at 4 weeks after stopping study treatment. The exact 95% CI for the percentage within treatment group was based on the Clopper-Pearson method.
Time frame: Posttreatment Week 4
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF for 8 Weeks | Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) | 97.8 percentage of participants |
| LDV/SOF for 12 Weeks | Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) | 100.0 percentage of participants |
| LDV/SOF for 24 Weeks | Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) | 84.2 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 up to Posttreatment Week 24
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF for 8 Weeks | Percentage of Participants With Virologic Failure | 0 percentage of participants |
| LDV/SOF for 12 Weeks | Percentage of Participants With Virologic Failure | 0 percentage of participants |
| LDV/SOF for 24 Weeks | Percentage of Participants With Virologic Failure | 0 percentage of participants |
Secondary
Pharmacokinetics (PK) Parameter: AUCtau of LDV
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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2))
Population: The PK Analysis Set included all participants who took at least 1 dose of the study drug and had at least 1 nonmissing postdose concentration value for the corresponding analyte in plasma.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LDV/SOF for 8 Weeks | Pharmacokinetics (PK) Parameter: AUCtau of LDV | 11923.9 h*ng/mL | Standard Deviation 6319.41 |
| LDV/SOF for 12 Weeks | Pharmacokinetics (PK) Parameter: AUCtau of LDV | 13632.7 h*ng/mL | Standard Deviation 4648.74 |
| LDV/SOF for 24 Weeks | Pharmacokinetics (PK) Parameter: AUCtau of LDV | 13542.5 h*ng/mL | Standard Deviation 6322.88 |
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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2))
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LDV/SOF for 8 Weeks | PK Parameter: AUCtau of GS-331007 (Metabolite of SOF) | 234980.1 h*ng/mL | Standard Deviation 67648.52 |
| LDV/SOF for 12 Weeks | PK Parameter: AUCtau of GS-331007 (Metabolite of SOF) | 269050.3 h*ng/mL | Standard Deviation 93600.65 |
| LDV/SOF for 24 Weeks | PK Parameter: AUCtau of GS-331007 (Metabolite of SOF) | 280829.5 h*ng/mL | Standard Deviation 93618.16 |
Secondary
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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2))
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LDV/SOF for 8 Weeks | PK Parameter: AUCtau of SOF | 2435.4 h*ng/mL | Standard Deviation 452.83 |
| LDV/SOF for 12 Weeks | PK Parameter: AUCtau of SOF | 2296.6 h*ng/mL | Standard Deviation 583.3 |
| LDV/SOF for 24 Weeks | PK Parameter: AUCtau of SOF | 2838.2 h*ng/mL | Standard Deviation 438.93 |
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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2))
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LDV/SOF for 8 Weeks | PK Parameter: Cmax of GS-331007 (Metabolite of SOF) | 9956.3 ng/mL | Standard Deviation 2846.07 |
| LDV/SOF for 12 Weeks | PK Parameter: Cmax of GS-331007 (Metabolite of SOF) | 11392.7 ng/mL | Standard Deviation 3938.33 |
| LDV/SOF for 24 Weeks | PK Parameter: Cmax of GS-331007 (Metabolite of SOF) | 11882.4 ng/mL | Standard Deviation 3951.04 |
Secondary
PK Parameter: Cmax of LDV
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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2))
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LDV/SOF for 8 Weeks | PK Parameter: Cmax of LDV | 544.2 ng/mL | Standard Deviation 271.72 |
| LDV/SOF for 12 Weeks | PK Parameter: Cmax of LDV | 618.4 ng/mL | Standard Deviation 204.87 |
| LDV/SOF for 24 Weeks | PK Parameter: Cmax of LDV | 607.0 ng/mL | Standard Deviation 267.38 |
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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2))
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LDV/SOF for 8 Weeks | PK Parameter: Cmax of SOF | 1059.8 ng/mL | Standard Deviation 251.74 |
| LDV/SOF for 12 Weeks | PK Parameter: Cmax of SOF | 1005.8 ng/mL | Standard Deviation 204.54 |
| LDV/SOF for 24 Weeks | PK Parameter: Cmax of SOF | 1052.5 ng/mL | Standard Deviation 295.06 |