Hepatitis C Virus Infection
Conditions
Brief summary
The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of sofosbuvir /velpatasvir (SOF/VEL) fixed-dose combination (FDC) in participants with chronic hepatitis C virus (HCV) who have received a liver transplant.
Interventions
DRUGSOF/VEL
400/100 mg 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: * History of chronic HCV infection (≥ 6 months) * HCV genotype 1, 2, 3, 4, 5, 6, or indeterminate * Liver transplant ≥ 3 months prior to screening * Male and nonpregnant/ non-lactating female individuals without cirrhosis or with compensated cirrhosis Key
Exclusion criteria
* History of clinically significant illness or any other medical disorder that may interfere with individual's treatment, assessment or compliance with the protocol, * Co-infection with HIV or hepatitis B virus * Known hypersensitivity to study medication, * Use of any prohibited concomitant medications as within with window before the Day 1 visit. * De novo or recurrent hepatocellular carcinoma posttransplant NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Cessation of Therapy (SVR12) | Posttreatment Week 12 | SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) at 12 weeks after stopping study treatment. |
| Percentage of Participants Who Prematurely Discontinued Study Drug Due to Any Adverse Event | Up to 12 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HCV RNA < LLOQ at Week 4 | Week 4 | — |
| Percentage of Participants With HCV RNA < LLOQ at Week 8 | Week 8 | — |
| Percentage of Participants With HCV RNA < LLOQ at Week 12 | Week 12 | — |
| HCV RNA at Week 2 | Week 2 | — |
| HCV RNA at Week 4 | Week 4 | — |
| HCV RNA at Week 8 | Week 8 | — |
| Percentage of Participants With Sustained Virologic Response 4 Weeks After Cessation of Therapy (SVR4) | Posttreatment Week 4 | SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping study treatment. |
| Change From Baseline in HCV RNA at Week 2 | Baseline; Week 2 | — |
| Change From Baseline in HCV RNA at Week 4 | Baseline; Week 4 | — |
| Change From Baseline in HCV RNA at Week 8 | Baseline; Week 8 | — |
| Change From Baseline in HCV RNA at Week 12 | Baseline; Week 12 | — |
| Percentage of Participants With Virologic Failure | Up to Posttreatment Week 12 | Virologic failure was defined as On-treatment virologic failure: * Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ on 2 consecutive measurements 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 12 weeks of treatment) Virologic relapse: * HCV RNA ≥ LLOQ during the post-treatment period having achieved HCV RNA \< LLOQ at end of treatment, confirmed with 2 consecutive values or last available post-treatment measurement |
| HCV RNA at Week 12 | Week 12 | — |
| Percentage of Participants With HCV RNA < LLOQ at Week 2 | Week 2 | — |
Countries
Spain, Switzerland, United Kingdom
Participant flow
Recruitment details
Participants were enrolled at study sites in Spain, Switzerland, and the United Kingdom. The first participant was screened on 27 July 2016. The last study visit occurred on 28 July 2017.
Pre-assignment details
85 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| SOF/VEL SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant | 79 |
| Total | 79 |
Baseline characteristics
| Characteristic | SOF/VEL |
|---|---|
| Age, Continuous | 62 Years STANDARD_DEVIATION 8.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 77 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HCV genotype Genotype 1 | 37 Participants |
| HCV genotype Genotype 2 | 3 Participants |
| HCV genotype Genotype 3 | 35 Participants |
| HCV genotype Genotype 4 | 4 Participants |
| HCV RNA | 6.4 log10 IU/mL STANDARD_DEVIATION 0.55 |
| HCV RNA Category < 800,000 IU/mL | 18 Participants |
| HCV RNA Category ≥ 800,000 IU/mL | 61 Participants |
| IL28b Status CC | 39 Participants |
| IL28b Status CT | 34 Participants |
| IL28b Status TT | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 2 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 | 65 Participants |
| Region of Enrollment Spain | 31 Participants |
| Region of Enrollment Switzerland | 7 Participants |
| Region of Enrollment United Kingdom | 41 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 79 |
| other Total, other adverse events | 42 / 79 |
| serious Total, serious adverse events | 3 / 79 |
Outcome results
Primary
Percentage of Participants Who Prematurely Discontinued Study Drug Due to Any Adverse Event
Time frame: Up to 12 weeks
Population: Safety Analysis Set: participants who took at least 1 dose if the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL | Percentage of Participants Who Prematurely Discontinued Study Drug Due to Any Adverse Event | 1.3 percentage of participants |
Primary
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Cessation of Therapy (SVR12)
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) at 12 weeks after stopping study treatment.
Time frame: Posttreatment Week 12
Population: Full Analysis Set: all enrolled participants who took at least 1 dose of the study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Cessation of Therapy (SVR12) | 96.2 percentage of participants |
Secondary
Change From Baseline in HCV RNA at Week 12
Time frame: Baseline; Week 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOF/VEL | Change From Baseline in HCV RNA at Week 12 | -5.22 log10 IU/mL | Standard Deviation 0.554 |
Secondary
Change From Baseline in HCV RNA at Week 2
Time frame: Baseline; Week 2
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOF/VEL | Change From Baseline in HCV RNA at Week 2 | -4.75 log10 IU/mL | Standard Deviation 0.635 |
Secondary
Change From Baseline in HCV RNA at Week 4
Time frame: Baseline; Week 4
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOF/VEL | Change From Baseline in HCV RNA at Week 4 | -5.13 log10 IU/mL | Standard Deviation 0.551 |
Secondary
Change From Baseline in HCV RNA at Week 8
Time frame: Baseline; Week 8
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOF/VEL | Change From Baseline in HCV RNA at Week 8 | -5.20 log10 IU/mL | Standard Deviation 0.548 |
Secondary
HCV RNA at Week 12
Time frame: Week 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOF/VEL | HCV RNA at Week 12 | 1.15 log10 IU/mL | Standard Deviation 0 |
Secondary
HCV RNA at Week 2
Time frame: Week 2
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOF/VEL | HCV RNA at Week 2 | 1.59 log10 IU/mL | Standard Deviation 0.596 |
Secondary
HCV RNA at Week 4
Time frame: Week 4
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOF/VEL | HCV RNA at Week 4 | 1.23 log10 IU/mL | Standard Deviation 0.251 |
Secondary
HCV RNA at Week 8
Time frame: Week 8
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SOF/VEL | HCV RNA at Week 8 | 1.15 log10 IU/mL | Standard Deviation 0 |
Secondary
Percentage of Participants With HCV RNA < LLOQ at Week 12
Time frame: Week 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL | Percentage of Participants With HCV RNA < LLOQ at Week 12 | 100.0 percentage of participants |
Secondary
Percentage of Participants With HCV RNA < LLOQ at Week 2
Time frame: Week 2
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL | Percentage of Participants With HCV RNA < LLOQ at Week 2 | 40.5 percentage of participants |
Secondary
Percentage of Participants With HCV RNA < LLOQ at Week 4
Time frame: Week 4
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL | Percentage of Participants With HCV RNA < LLOQ at Week 4 | 85.9 percentage of participants |
Secondary
Percentage of Participants With HCV RNA < LLOQ at Week 8
Time frame: Week 8
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL | Percentage of Participants With HCV RNA < LLOQ at Week 8 | 98.7 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response 4 Weeks After Cessation 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 | Percentage of Participants With Sustained Virologic Response 4 Weeks After Cessation of Therapy (SVR4) | 97.5 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 on 2 consecutive measurements 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 12 weeks of treatment) Virologic relapse: * HCV RNA ≥ LLOQ during the post-treatment period having achieved HCV RNA \< LLOQ at end of treatment, confirmed with 2 consecutive values or last available post-treatment measurement
Time frame: Up to Posttreatment Week 12
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL | Percentage of Participants With Virologic Failure | 2.5 percentage of participants |