Hepatitis C Infection With HIV Co-Infection
Conditions
Brief summary
The primary objectives of this study are to determine the antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) in adults with acute genotype 1 or 4 hepatitis C virus (HCV) and chronic human immunodeficiency virus (HIV)-1 co-infection.
Interventions
DRUGLDV/SOF
90/400 mg FDC 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: * Acute, untreated, hepatitis C infection, genotype 1 or 4, with an estimated duration less than 24 weeks * Confirmed HIV-1 infection * CD4 T cell count \>200/μL for individuals receiving antiretroviral therapy (ART), CD4 T cell count \> 500/μL at screening for individuals without ART * Use of two effective contraception methods if female of childbearing potential or sexually active male with female partner Key
Exclusion criteria
* Pregnant or nursing female or male with pregnant female partner * Chronic liver disease of a non HCV etiology * Coinfection with hepatitis B virus (HBV) * Treatment with any investigational drug or device within 60 days of the screening visit. * History of clinically significant illness or any other medical disorder that may interfere with the individual's treatment, assessment or compliance with the protocol Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Completion of Treatment (SVR12) | Posttreatment Week 12 | SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug. |
| Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | Up to 6 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HCV RNA at Weeks 2, 4, and 6 | Baseline; Weeks 2, 4, and 6 | — |
| Percentage of Participants With Virologic Failure | Up to Posttreatment Week 12 | Virologic failure was defined as: * On-treatment virologic failure * confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ, while on treatment (ie, breakthrough), * confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment (ie, rebound), * HCV RNA persistently ≥ LLOQ through end of treatment (ie, nonresponse) * Relapse * HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement |
| Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Study Treatment (SVR4) | Posttreatment Week 4 | SVR4 was defined as HCV RNA \< LLOQ 4 weeks after the last dose of study drug. |
| Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4 | Weeks 2, 4, 6, and Posttreatment Week 4 | — |
| Percent Change From Baseline in CD4 T-cell Count at the End of Treatment and at Posttreatment Week 4 | Baseline; Week 6; Posttreatment Week 4 | — |
| Change in HIV RNA From Day 1 to End of Treatment as Assessed by Proportion of Participants Who Had Confirmed HIV Virologic Rebound During the Study. | Day 1; Week 6 | Participants with HIV virologic rebound was defined as participants with at least two HIV RNA ≥ 400 copies/mL at 2 consecutive post-baseline visits which are at least 2 weeks apart based on actual dates. |
| Percentage of Participants With HCV RNA < LLOQ on Treatment | Weeks 2, 4, and 6 | — |
Countries
Germany, United Kingdom
Participant flow
Recruitment details
Participants were enrolled at study sites in Germany and the United Kingdom. The first participant was screened on 11 June 2015. The last study visit occurred on 8 January 2016.
Pre-assignment details
34 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| LDV/SOF LDV/SOF 90/400 mg FDC tablet administered once daily for 6 weeks | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 3 |
Baseline characteristics
| Characteristic | LDV/SOF |
|---|---|
| Age, Continuous | 41 years STANDARD_DEVIATION 8.8 |
| CD4 Counts | 675 cells/uL STANDARD_DEVIATION 251.3 |
| HCV Genotype Genotype 1a | 19 Participants |
| HCV Genotype Genotype 4 | 7 Participants |
| HCV RNA | 5.4 log10 IU/mL STANDARD_DEVIATION 1.6 |
| HCV RNA Category < 800,000 IU/mL | 14 Participants |
| HCV RNA Category >= 800,000 IU/mL | 12 Participants |
| IL28b Status CC | 12 Participants |
| IL28b Status CT | 11 Participants |
| IL28b Status TT | 3 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants |
| Race/Ethnicity, Customized Not Disclosed | 3 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 22 Participants |
| Race/Ethnicity, Customized White | 24 Participants |
| Region of Enrollment Germany | 15 Participants |
| Region of Enrollment United Kingdom | 11 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 20 / 26 |
| serious Total, serious adverse events | 1 / 26 |
Outcome results
Primary
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Time frame: Up to 6 weeks
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF | Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | 0 percentage of participants |
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks After Completion of Treatment (SVR12)
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
Time frame: Posttreatment Week 12
Population: Full Analysis Set: participants with genotype 1 or 4 HCV infection who were enrolled into the study and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF | Percentage of Participants With Sustained Virologic Response 12 Weeks After Completion of Treatment (SVR12) | 76.9 percentage of participants |
Secondary
Change From Baseline in HCV RNA at Weeks 2, 4, and 6
Time frame: Baseline; Weeks 2, 4, and 6
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDV/SOF | Change From Baseline in HCV RNA at Weeks 2, 4, and 6 | Change at Week 2 | -4.01 log10 IU/mL | Standard Deviation 1.497 |
| LDV/SOF | Change From Baseline in HCV RNA at Weeks 2, 4, and 6 | Change at Week 4 | -4.16 log10 IU/mL | Standard Deviation 1.583 |
| LDV/SOF | Change From Baseline in HCV RNA at Weeks 2, 4, and 6 | Change at Week 6 | -4.17 log10 IU/mL | Standard Deviation 1.583 |
Secondary
Change in HIV RNA From Day 1 to End of Treatment as Assessed by Proportion of Participants Who Had Confirmed HIV Virologic Rebound During the Study.
Participants with HIV virologic rebound was defined as participants with at least two HIV RNA ≥ 400 copies/mL at 2 consecutive post-baseline visits which are at least 2 weeks apart based on actual dates.
Time frame: Day 1; Week 6
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LDV/SOF | Change in HIV RNA From Day 1 to End of Treatment as Assessed by Proportion of Participants Who Had Confirmed HIV Virologic Rebound During the Study. | 0 Participants |
Secondary
Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4
Time frame: Weeks 2, 4, 6, and Posttreatment Week 4
Population: Participants in the Safety Analysis Set who had HIV-1 RNA \< 50 copies/mL at Baseline were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF | Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4 | Week 2 | 100.0 percentage of participants |
| LDV/SOF | Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4 | Week 4 | 100.0 percentage of participants |
| LDV/SOF | Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4 | Week 6 | 95.2 percentage of participants |
| LDV/SOF | Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4 | Posttreatment Week 4 | 100.0 percentage of participants |
Secondary
Percentage of Participants With HCV RNA < LLOQ on Treatment
Time frame: Weeks 2, 4, and 6
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 2 | 73.1 percentage of participants |
| LDV/SOF | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 88.5 percentage of participants |
| LDV/SOF | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 6 | 96.2 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Study Treatment (SVR4)
SVR4 was defined as HCV RNA \< LLOQ 4 weeks after the last dose of study drug.
Time frame: Posttreatment Week 4
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF | Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Study Treatment (SVR4) | 84.6 percentage of participants |
Secondary
Percentage of Participants With Virologic Failure
Virologic failure was defined as: * On-treatment virologic failure * confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ, while on treatment (ie, breakthrough), * confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment (ie, rebound), * HCV RNA persistently ≥ LLOQ through end of treatment (ie, nonresponse) * Relapse * HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement
Time frame: Up to Posttreatment Week 12
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF | Percentage of Participants With Virologic Failure | 15.4 percentage of participants |
Secondary
Percent Change From Baseline in CD4 T-cell Count at the End of Treatment and at Posttreatment Week 4
Time frame: Baseline; Week 6; Posttreatment Week 4
Population: Participants in the Safety Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDV/SOF | Percent Change From Baseline in CD4 T-cell Count at the End of Treatment and at Posttreatment Week 4 | Change at Week 6 | -0.3 percent change | Standard Deviation 4.91 |
| LDV/SOF | Percent Change From Baseline in CD4 T-cell Count at the End of Treatment and at Posttreatment Week 4 | Change at Posttreatment Week 4 | 0.4 percent change | Standard Deviation 4.08 |