Chronic HCV Infection
Conditions
Brief summary
The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of treatment with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) in treatment-naive and treatment-experienced participants with chronic genotype 1 hepatitis C virus (HCV) infection.
Interventions
DRUGLDV/SOF
90/400 mg FDC tablet administered orally once daily without regard to food
Sponsors
Gilead Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Willing and able to provide written informed consent * HCV RNA ≥ 10\^4 IU/mL at screening * HCV treatment-naive, as defined as no prior exposure to any interferon (IFN) or other approved or experimental HCV-specific direct-acting antiviral agent; OR HCV treatment-experienced with medical records that include sufficient detail of prior IFN-based treatment to allow for categorization of prior response as either intolerant, non-responder, or experienced viral breakthrough or relapse. * Genotype 1 HCV at screening * HCV infection documented by anti-HCV antibody test, genotyping test, or liver biopsy Key
Exclusion criteria
* Pregnant or nursing female * Chronic liver disease of a non-HCV etiology * Current or prior history of any clinically-significant illness (other than HCV) * Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) NOTE: Other protocol defined Inclusion/
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, \< 25 IU/mL in Korea and Taiwan and \< 15 IU/mL in China) 12 weeks following the last dose of study drug. |
| Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event | Up to 12 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HCV RNA and Change From Baseline in HCV RNA Through Week 12 for China Only | Baseline; Week 12 | — |
| Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | Posttreatment Weeks 4 and 24 | SVR4 and SVR24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks following the last dose of study drug, respectively. |
| Percentage of Participants Experiencing Viral Relapse | Week 12 to Posttreatment Week 24 | Viral relapse is defined as having achieved undetectable HCV RNA levels (HCV RNA \< LLOQ) within 4 weeks of end of treatment, but did not achieve an SVR. |
| Percentage of Participants Experiencing Viral Breakthrough | Up to 12 weeks | Viral breakthrough were defined as having achieved undetectable HCV RNA levels (HCV RNA \< LLOQ) during treatment, but did not achieve a sustained virologic response (SVR). |
Countries
China, South Korea, Taiwan
Participant flow
Recruitment details
Participants were enrolled at study sites in Mainland China (referred to as China throughout this results record), Korea, and Taiwan. The first participant was screened on 10 December 2013. The last study visit occurred on 29 September 2017.
Pre-assignment details
416 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| LDV/SOF LDV/SOF (90/400 mg) FDC tablet administered once daily without regard to food for 12 weeks in treatment-experienced and treatment-naive participants in China, Korea, and Taiwan | 384 |
| Total | 384 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrew Consent | 2 |
Baseline characteristics
| Characteristic | LDV/SOF |
|---|---|
| Age, Continuous | 51 Years STANDARD_DEVIATION 13 |
| IL28B CC | 286 Participants |
| IL28B CT | 95 Participants |
| IL28B TT | 3 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 384 Participants |
| Race/Ethnicity, Customized Race Subcategory Chinese | 207 Participants |
| Race/Ethnicity, Customized Race Subcategory Korean | 93 Participants |
| Race/Ethnicity, Customized Race Subcategory Other (Taiwanese- Chinese) | 1 Participants |
| Race/Ethnicity, Customized Race Subcategory Taiwanese | 83 Participants |
| Region of Enrollment China | 206 Participants |
| Region of Enrollment South Korea | 93 Participants |
| Region of Enrollment Taiwan | 85 Participants |
| Sex: Female, Male Female | 202 Participants |
| Sex: Female, Male Male | 182 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 384 |
| other Total, other adverse events | 105 / 384 |
| serious Total, serious adverse events | 7 / 384 |
Outcome results
Primary
Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event
Time frame: Up to 12 weeks
Population: Safety Analysis Set: participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF: China | Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event | 0 percentage of participants |
| LDV/SOF: Overall | Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event | 0.5 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, \< 25 IU/mL in Korea and Taiwan and \< 15 IU/mL in China) 12 weeks following the last dose of study drug.
Time frame: Posttreatment Week 12
Population: Full analysis set: participants who were enrolled and received at least 1 dose of study drug, and have chronic genotype 1 HCV infection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF: China | Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 Percentage of participants |
| LDV/SOF: Overall | Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | 99.2 Percentage of participants |
Comparison: A sample size of 100 Chinese participants in the treatment naive group provided at least 90% power to detect a 17% improvement in SVR12 rate from the historical control rate of 57% using 2-sided exact one-sample binomial test at significant level of 0.05.p-value: <0.001Binomial Exact Test
Secondary
HCV RNA and Change From Baseline in HCV RNA Through Week 12 for China Only
Time frame: Baseline; Week 12
Population: Only Chinese participants in the Full Analysis set were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDV/SOF: China | HCV RNA and Change From Baseline in HCV RNA Through Week 12 for China Only | Change at Week 12 | -5.16 log10 IU/mL | Standard Deviation 0.633 |
| LDV/SOF: China | HCV RNA and Change From Baseline in HCV RNA Through Week 12 for China Only | Baseline | 6.31 log10 IU/mL | Standard Deviation 0.633 |
Secondary
Percentage of Participants Experiencing Viral Breakthrough
Viral breakthrough were defined as having achieved undetectable HCV RNA levels (HCV RNA \< LLOQ) during treatment, but did not achieve a sustained virologic response (SVR).
Time frame: Up to 12 weeks
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF: China | Percentage of Participants Experiencing Viral Breakthrough | 0 percentage of participants |
| LDV/SOF: Overall | Percentage of Participants Experiencing Viral Breakthrough | 0 percentage of participants |
Secondary
Percentage of Participants Experiencing Viral Relapse
Viral relapse is defined as having achieved undetectable HCV RNA levels (HCV RNA \< LLOQ) within 4 weeks of end of treatment, but did not achieve an SVR.
Time frame: Week 12 to Posttreatment Week 24
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF: China | Percentage of Participants Experiencing Viral Relapse | 0 percentage of participants |
| LDV/SOF: Overall | Percentage of Participants Experiencing Viral Relapse | 0.5 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4 and SVR24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Time frame: Posttreatment Weeks 4 and 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF: China | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 100.0 percentage of participants |
| LDV/SOF: China | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 100.0 percentage of participants |
| LDV/SOF: Overall | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 99.2 percentage of participants |
| LDV/SOF: Overall | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 99.0 percentage of participants |