Hepatitis C Virus Infection
Conditions
Brief summary
The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of therapy with Sofosbuvir/Velpatasvir (SOF/VEL) Fixed-Dose Combination (FDC) and Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX ) FDC in participants with chronic HCV infection.
Interventions
DRUGSOF/VEL
400/100 mg FDC tablet orally once daily.
DRUGSOF/VEL/VOX
400/100/100 mg FDC tablet orally once daily.
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Chronic HCV infected males and non-pregnant/non-lactating females * Treatment-naive or treatment-experienced individuals * Non-cirrhosis or compensated cirrhosis at 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) < Lower Limit of Quantification (LLOQ) 12 Weeks After Discontinuation of Study Treatment | Posttreatment Week 12 | SVR12 was defined as HCV RNA \< LLOQ (i.e., 15 IU/mL) at 12 weeks after stopping study treatment. |
| Percentage of Participants Who Permanently Discontinued the Study Drug Due to an Adverse Event | First dose date up to 12 weeks plus 30 days | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2, Week 4, Week 8, Week 12 | LLOQ was 15 IU/mL. |
| Percentage of Participants With SVR < LLOQ 4 Weeks After Discontinuation of Study Treatment | Posttreatment Week 4 | SVR4 was defined as HCV RNA \< LLOQ (i.e.15 IU/mL) 4 weeks after stopping study treatment. |
| Number of Participants With Alanine Aminotransferase (ALT) Normalization | Baseline, Week 2, Week 4, Week 8, Week 12 | Number of participants with ALT normalization, defined as ALT \> upper limit of normal (ULN) (ULN = 43 U/L) at baseline and ALT ≤ ULN, at each visit was presented. |
| Change From Baseline in HCV RNA | Baseline, Week 2, Week 4, Week 8, Week 12 | — |
| Percentage of Participants With Virologic Failure | Baseline up to Posttreatment Week 12 | Virologic failure was defined as: On-treatment virologic failure: * Breakthrough (HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ, while on treatment, confirmed with 2 consecutive values), 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
South Korea
Participant flow
Recruitment details
Participants were enrolled at study sites in South Korea. The first participant was screened on 03 January 2020. The last study visit occurred on 12 November 2020.
Pre-assignment details
96 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| SOF/VEL Participants with chronic HCV infection (genotype 1 or 2), who were treatment-naive or treatment-experienced with IFN-based treatments received SOF/VEL 400/100 mg FDC tablet orally once daily for 12 weeks. | 54 |
| SOF/VEL/VOX Participants with chronic HCV infection (genotype 1 or 2), who were treatment-experienced with NS5A DAA-based treatments of at least a 4 weeks duration received SOF/VEL/VOX 400/100/100 mg FDC tablet orally once daily for 12 weeks. | 33 |
| Total | 87 |
Baseline characteristics
| Characteristic | SOF/VEL | SOF/VEL/VOX | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 20 Participants | 16 Participants | 36 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 17 Participants | 51 Participants |
| Genotype Genotype 1 | 27 Participants | 32 Participants | 59 Participants |
| Genotype Genotype 2 | 27 Participants | 1 Participants | 28 Participants |
| HCV RNA Category < 800,000 IU/mL | 24 participants | 3 participants | 27 participants |
| HCV RNA Category ≥ 800,000 IU/mL | 30 participants | 30 participants | 60 participants |
| Interleukin-28B gene (IL28b) Status CC | 41 participants | 23 participants | 64 participants |
| Interleukin-28B gene (IL28b) Status CT | 13 participants | 9 participants | 22 participants |
| Interleukin-28B gene (IL28b) Status Missing | 0 participants | 1 participants | 1 participants |
| Interleukin-28B gene (IL28b) Status TT | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 53 Participants | 33 Participants | 86 Participants |
| Race/Ethnicity, Customized Ethnicity Not Permitted | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 54 Participants | 33 Participants | 87 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 29 Participants | 18 Participants | 47 Participants |
| Sex: Female, Male Male | 25 Participants | 15 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 54 | 0 / 33 |
| other Total, other adverse events | 5 / 54 | 8 / 33 |
| serious Total, serious adverse events | 3 / 54 | 1 / 33 |
Outcome results
Primary
Percentage of Participants Who Permanently Discontinued the Study Drug Due to an Adverse Event
Time frame: First dose date up to 12 weeks plus 30 days
Population: Safety Analysis Set included all participants who took at least 1 dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL | Percentage of Participants Who Permanently Discontinued the Study Drug Due to an Adverse Event | 1.9 percentage of participants |
| SOF/VEL/VOX | 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 (SVR) < Lower Limit of Quantification (LLOQ) 12 Weeks After Discontinuation of Study Treatment
SVR12 was defined as HCV RNA \< LLOQ (i.e., 15 IU/mL) at 12 weeks after stopping study treatment.
Time frame: Posttreatment Week 12
Population: Full Analysis Set included all enrolled participants who took at least 1 dose of study drug and had detectable HCV RNA at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL | Percentage of Participants With Sustained Virologic Response (SVR) < Lower Limit of Quantification (LLOQ) 12 Weeks After Discontinuation of Study Treatment | 98.1 percentage of participants |
| SOF/VEL/VOX | Percentage of Participants With Sustained Virologic Response (SVR) < Lower Limit of Quantification (LLOQ) 12 Weeks After Discontinuation of Study Treatment | 100 percentage of participants |
Secondary
Change From Baseline in HCV RNA
Time frame: Baseline, Week 2, Week 4, Week 8, Week 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOF/VEL | Change From Baseline in HCV RNA | Change at Week 2 | -4.78 log10 IU/mL | Standard Deviation 0.857 |
| SOF/VEL | Change From Baseline in HCV RNA | Change at Week 8 | -4.79 log10 IU/mL | Standard Deviation 0.867 |
| SOF/VEL | Change From Baseline in HCV RNA | Change at Week 4 | -4.81 log10 IU/mL | Standard Deviation 0.866 |
| SOF/VEL | Change From Baseline in HCV RNA | Change at Week 12 | -4.79 log10 IU/mL | Standard Deviation 0.867 |
| SOF/VEL | Change From Baseline in HCV RNA | Baseline | 5.95 log10 IU/mL | Standard Deviation 0.866 |
| SOF/VEL/VOX | Change From Baseline in HCV RNA | Change at Week 12 | -5.33 log10 IU/mL | Standard Deviation 0.354 |
| SOF/VEL/VOX | Change From Baseline in HCV RNA | Baseline | 6.48 log10 IU/mL | Standard Deviation 0.354 |
| SOF/VEL/VOX | Change From Baseline in HCV RNA | Change at Week 2 | -5.19 log10 IU/mL | Standard Deviation 0.545 |
| SOF/VEL/VOX | Change From Baseline in HCV RNA | Change at Week 4 | -5.33 log10 IU/mL | Standard Deviation 0.354 |
| SOF/VEL/VOX | Change From Baseline in HCV RNA | Change at Week 8 | -5.33 log10 IU/mL | Standard Deviation 0.354 |
Secondary
Number of Participants With Alanine Aminotransferase (ALT) Normalization
Number of participants with ALT normalization, defined as ALT \> upper limit of normal (ULN) (ULN = 43 U/L) at baseline and ALT ≤ ULN, at each visit was presented.
Time frame: Baseline, Week 2, Week 4, Week 8, Week 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF/VEL | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Week 2 (ALT≤ ULN) | 21 participants |
| SOF/VEL | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Week 8 (ALT≤ ULN) | 19 participants |
| SOF/VEL | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Baseline (ALT>ULN) | 21 participants |
| SOF/VEL | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Week 12 (ALT≤ ULN) | 17 participants |
| SOF/VEL | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Week 4 (ALT≤ ULN) | 21 participants |
| SOF/VEL/VOX | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Week 12 (ALT≤ ULN) | 13 participants |
| SOF/VEL/VOX | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Week 2 (ALT≤ ULN) | 13 participants |
| SOF/VEL/VOX | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Week 4 (ALT≤ ULN) | 13 participants |
| SOF/VEL/VOX | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Week 8 (ALT≤ ULN) | 13 participants |
| SOF/VEL/VOX | Number of Participants With Alanine Aminotransferase (ALT) Normalization | Baseline (ALT>ULN) | 16 participants |
Secondary
Percentage of Participants With HCV RNA < LLOQ on Treatment
LLOQ was 15 IU/mL.
Time frame: Week 2, Week 4, Week 8, Week 12
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF/VEL | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 90.6 percentage of participants |
| SOF/VEL | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 100.0 percentage of participants |
| SOF/VEL | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 100.0 percentage of participants |
| SOF/VEL | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 12 | 100.0 percentage of participants |
| SOF/VEL/VOX | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 12 | 100.0 percentage of participants |
| SOF/VEL/VOX | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 69.7 percentage of participants |
| SOF/VEL/VOX | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 100.0 percentage of participants |
| SOF/VEL/VOX | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 100.0 percentage of participants |
Secondary
Percentage of Participants With SVR < LLOQ 4 Weeks After Discontinuation of Study Treatment
SVR4 was defined as HCV RNA \< LLOQ (i.e.15 IU/mL) 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 | Percentage of Participants With SVR < LLOQ 4 Weeks After Discontinuation of Study Treatment | 98.1 percentage of participants |
| SOF/VEL/VOX | Percentage of Participants With SVR < LLOQ 4 Weeks After Discontinuation of Study Treatment | 100 percentage of participants |
Secondary
Percentage of Participants With Virologic Failure
Virologic failure was defined as: On-treatment virologic failure: * Breakthrough (HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ, while on treatment, confirmed with 2 consecutive values), 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 12
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL | Percentage of Participants With Virologic Failure | 1.9 percentage of participants |
| SOF/VEL/VOX | Percentage of Participants With Virologic Failure | 0 percentage of participants |