Chronic Genotype 4 HCV, Chronic Genotype 5 HCV
Conditions
Keywords
HCV GT 4, HCV GT 5
Brief summary
This study is to evaluate the efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) in participants with chronic genotype 4 or 5 hepatitis C virus (HCV) infection as measured by the proportion of subjects with sustained virologic response (SVR12), defined as HCV RNA \< lower limit of quantification (LLOQ) 12 weeks after discontinuation of therapy.
Interventions
DRUGLDV/SOF
LDV/SOF (90/400 mg) 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
* HCV RNA ≥ 10\^4 IU/mL at screening * Chronic genotype 4 or 5 HCV Infection * Individuals may be treatment naive or treatment experienced * Presence or absence of cirrhosis, a liver biopsy may be required * Healthy according to medical history and physical examination with the exception of HCV diagnosis * Agree to use two forms of highly effective contraception for the duration of the study
Exclusion criteria
* History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the individual's participation for the full duration of the study or not be in the best interest of the individual in the opinion of the investigator * Prior exposure to approved or experimental HCV specific direct acting antiviral(s) (DAA) other than NS3/4A protease inhibitors * History of any other clinically significant chronic liver disease * Evidence of or history of decompensated liver disease * HIV or chronic hepatitis B (HBV) infection * Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers) * Chronic use of immunosuppressive agents or immunomodulatory agents
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 HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment. |
| Percentage of Participants Who Permanently Discontinued LDV/SOF Due to an Adverse Event | Up to 12 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | Posttreatment Weeks 4 and 24 | SVR4 and SVR 24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively. |
| Percentage of Patients With Virologic Failure | Up to posttreatment Week 24 | Virologic failure was defined as either: * 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); or * Relapse: * HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while receiving treatment |
| Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Baseline; Weeks 2, 4, 8, and 12 | — |
Countries
France
Participant flow
Recruitment details
Participants were enrolled at study sites in France. The first participant was screened on 07 March 2014. The last study visit occurred on 17 February 2015.
Pre-assignment details
91 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Genotype 4: Treatment-naive LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-naive participants with genotype 4 HCV infection | 22 |
| Genotype 4: Treatment-experienced LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-experienced participants with genotype 4 HCV infection | 22 |
| Genotype 5: Treatment-naive LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-naive participants with genotype 5 HCV infection | 21 |
| Genotype 5: Treatment-experienced LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-experienced participants with genotype 5 HCV infection | 20 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 3 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Genotype 4: Treatment-naive | Genotype 4: Treatment-experienced | Genotype 5: Treatment-naive | Genotype 5: Treatment-experienced | Total |
|---|---|---|---|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 9.2 | 50 years STANDARD_DEVIATION 8.8 | 61 years STANDARD_DEVIATION 10.4 | 64 years STANDARD_DEVIATION 8.6 | 57 years STANDARD_DEVIATION 10.8 |
| Cirrhosis Status Absence | 21 participants | 13 participants | 18 participants | 14 participants | 66 participants |
| Cirrhosis Status Presence | 1 participants | 9 participants | 3 participants | 6 participants | 19 participants |
| HCV Genotype Genotype 4 | 22 participants | 22 participants | 0 participants | 0 participants | 44 participants |
| HCV Genotype Genotype 5 | 0 participants | 0 participants | 21 participants | 20 participants | 41 participants |
| HCV RNA | 6.0 log10 copies/mL STANDARD_DEVIATION 0.4 | 6.3 log10 copies/mL STANDARD_DEVIATION 0.48 | 6.2 log10 copies/mL STANDARD_DEVIATION 0.48 | 6.6 log10 copies/mL STANDARD_DEVIATION 0.39 | 6.3 log10 copies/mL STANDARD_DEVIATION 0.48 |
| IL28b Status CC | 7 participants | 1 participants | 13 participants | 6 participants | 27 participants |
| IL28b Status CT | 11 participants | 16 participants | 7 participants | 11 participants | 45 participants |
| IL28b Status TT | 4 participants | 5 participants | 1 participants | 3 participants | 13 participants |
| Race/Ethnicity, Customized Black or African American | 3 participants | 5 participants | 0 participants | 0 participants | 8 participants |
| Race/Ethnicity, Customized White | 19 participants | 17 participants | 21 participants | 20 participants | 77 participants |
| Region of Enrollment France | 22 participants | 22 participants | 21 participants | 20 participants | 85 participants |
| Sex: Female, Male Female | 11 Participants | 5 Participants | 10 Participants | 10 Participants | 36 Participants |
| Sex: Female, Male Male | 11 Participants | 17 Participants | 11 Participants | 10 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 44 | 31 / 41 |
| serious Total, serious adverse events | 0 / 44 | 1 / 41 |
Outcome results
Primary
Percentage of Participants Who Permanently Discontinued LDV/SOF Due to an Adverse Event
Time frame: Up to 12 weeks
Population: Safety Analysis Set: participants were enrolled and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Genotype 4: Treatment-naive | Percentage of Participants Who Permanently Discontinued LDV/SOF Due to an Adverse Event | 0 percentage of participants |
| Genotype 4: Treatment-experienced | Percentage of Participants Who Permanently Discontinued LDV/SOF 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 HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Time frame: Posttreatment Week 12
Population: Full Analysis Set: participants with genotype 4 or 5 HCV infection who were enrolled and received at least on dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Genotype 4: Treatment-naive | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 95.5 percentage of participants |
| Genotype 4: Treatment-experienced | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 90.9 percentage of participants |
| Genotype 5: Treatment-naive | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 95.2 percentage of participants |
| Genotype 5: Treatment-experienced | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 95.0 percentage of participants |
Secondary
Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12
Time frame: Baseline; Weeks 2, 4, 8, and 12
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotype 4: Treatment-naive | Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Change at Week 2 | -4.65 log10 IU/mL | Standard Deviation 0.397 |
| Genotype 4: Treatment-naive | Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Change at Week 4 | -4.86 log10 IU/mL | Standard Deviation 0.396 |
| Genotype 4: Treatment-naive | Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Change at Week 8 | -4.88 log10 IU/mL | Standard Deviation 0.401 |
| Genotype 4: Treatment-naive | Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Change at Week 12 | -4.88 log10 IU/mL | Standard Deviation 0.401 |
| Genotype 4: Treatment-experienced | Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Change at Week 4 | -5.17 log10 IU/mL | Standard Deviation 0.49 |
| Genotype 4: Treatment-experienced | Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Change at Week 8 | -5.18 log10 IU/mL | Standard Deviation 0.484 |
| Genotype 4: Treatment-experienced | Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Change at Week 12 | -5.18 log10 IU/mL | Standard Deviation 0.484 |
| Genotype 4: Treatment-experienced | Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Change at Week 2 | -4.77 log10 IU/mL | Standard Deviation 0.495 |
| Genotype 5: Treatment-naive | Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Change at Week 8 | -5.07 log10 IU/mL | Standard Deviation 0.474 |
| Genotype 5: Treatment-naive | Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Change at Week 4 | -5.07 log10 IU/mL | Standard Deviation 0.474 |
| Genotype 5: Treatment-naive | Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Change at Week 12 | -5.07 log10 IU/mL | Standard Deviation 0.474 |
| Genotype 5: Treatment-naive | Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Change at Week 2 | -4.97 log10 IU/mL | Standard Deviation 0.479 |
| Genotype 5: Treatment-experienced | Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Change at Week 12 | -5.45 log10 IU/mL | Standard Deviation 0.387 |
| Genotype 5: Treatment-experienced | Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Change at Week 4 | -5.39 log10 IU/mL | Standard Deviation 0.381 |
| Genotype 5: Treatment-experienced | Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Change at Week 2 | -4.94 log10 IU/mL | Standard Deviation 0.477 |
| Genotype 5: Treatment-experienced | Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12 | Change at Week 8 | -5.45 log10 IU/mL | Standard Deviation 0.387 |
Secondary
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4 and SVR 24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
Time frame: Posttreatment Weeks 4 and 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Genotype 4: Treatment-naive | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 95.5 percentage of participants |
| Genotype 4: Treatment-naive | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 95.5 percentage of participants |
| Genotype 4: Treatment-experienced | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 90.9 percentage of participants |
| Genotype 4: Treatment-experienced | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 90.9 percentage of participants |
| Genotype 5: Treatment-naive | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 95.2 percentage of participants |
| Genotype 5: Treatment-naive | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 95.2 percentage of participants |
| Genotype 5: Treatment-experienced | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 95.0 percentage of participants |
| Genotype 5: Treatment-experienced | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 95.0 percentage of participants |
Secondary
Percentage of Patients With Virologic Failure
Virologic failure was defined as either: * 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); or * Relapse: * HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while receiving treatment
Time frame: Up to posttreatment Week 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Genotype 4: Treatment-naive | Percentage of Patients With Virologic Failure | On-treatment Virologic Failure | 0 percentage of participants |
| Genotype 4: Treatment-naive | Percentage of Patients With Virologic Failure | Relapse | 4.5 percentage of participants |
| Genotype 4: Treatment-experienced | Percentage of Patients With Virologic Failure | Relapse | 9.1 percentage of participants |
| Genotype 4: Treatment-experienced | Percentage of Patients With Virologic Failure | On-treatment Virologic Failure | 0 percentage of participants |
| Genotype 5: Treatment-naive | Percentage of Patients With Virologic Failure | On-treatment Virologic Failure | 0 percentage of participants |
| Genotype 5: Treatment-naive | Percentage of Patients With Virologic Failure | Relapse | 4.8 percentage of participants |
| Genotype 5: Treatment-experienced | Percentage of Patients With Virologic Failure | On-treatment Virologic Failure | 0 percentage of participants |
| Genotype 5: Treatment-experienced | Percentage of Patients With Virologic Failure | Relapse | 5.0 percentage of participants |