HIV-1 Infection, HCV Infection
Conditions
Keywords
HIV, HCV, Antiretroviral therapy, HCV direct acting antiviral(s) (DAA)
Brief summary
This study will evaluate efficacy of ledipasvir/sofosbuvir (LDV/SOF) and safety and tolerability of switching to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or emtricitabine/rilpivirine/tenofovir alafenamide (F/R/TAF) from the current antiretroviral (ARV) therapy and in virologically-suppressed, HIV-1/HCV co-infected participants.
Interventions
DRUGE/C/F/TAF
150/150/200/10 mg fixed dose combination (FDC) tablet administered orally once daily
DRUGF/R/TAF
200/25/25 mg FDC tablet administered orally once daily
DRUGLDV/SOF
90/400 mg FDC tablet administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Chronic genotype (GT) 1, HCV infected, male and non-pregnant/ non-lactating female individuals, without cirrhosis, treatment-naive or treatment-experienced with interferon (IFN) +/- ribavirin (RBV) +/- HCV protease inhibitor (PI). * Compensated cirrhotic individuals must be HCV treatment-naive. * No prior treatments with NS5A and NS5B or any HCV direct acting antivirals, except boceprevir, telaprevir and simeprevir, in combination with IFN and RBV * Currently on an ARV regimen (2 NRTI + a third agent) without change for 6 months prior to screening. * Documented plasma HIV-1 RNA levels \< 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) for ≥ 6 months preceding the screening visit. After reaching HIV-1 RNA \< 50 copies/mL, single values (blips) of HIV-1 RNA ≥ 50 copies/mL followed by resuppression is allowed. * For individuals with 3 or more prior ARV regimens, a regimen history should be provided for approval by the Sponsor. * Note: Individuals that changed from TDF to TAF less than 6 months ago will be eligible as long as the TDF/ TAF change was the only change to the regimen. * Plasma HIV-1 RNA level \< 50 copies/mL at the screening visit * Have no documented resistance to any of the HIV study agents at time in the past, including but not limited to the reverse transcriptase resistance mutations K65R, K70E, K101E/P, E138A/G/K/R/Q, V179L, Y181C/I/V, M184V/I, Y188L, H221Y, F227C, M230I/L, the combination of K103N+L100I, or 3 or more thymidine analog associated mutations (TAMs) that include M41L or L210W (TAMs are M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R). If a historical genotype prior to first ARV is not available or individual had 3 or more prior ARV regimens, individual will have proviral genotype analysis for archived resistance prior to Day 1. * No history of HIV virologic failure * No evidence of Hepatitis B infection * Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min as estimated by Cockcroft-Gault formula Note: Other protocol defined Inclusion/
Exclusion criteria
may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HCV RNA < LLOQ at 12 Weeks After Discontinuation of LDV/SOF Treatment (SVR12) | HCV Posttreatment Week 12 | Sustained Virologic Response (SVR12) was defined as HCV RNA \< the lower limit of quantitation (LLOQ) at 12 weeks after stopping LDV/SOF treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HCV RNA < LLOQ at 4 Weeks After Discontinuation of LDV/SOF Treatment (SVR4) | HCV Posttreatment Week 4 | SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping LDV/SOF treatment. |
| Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL (Virologic Failure) 24 Weeks After Start of the F/TAF-Based Regimen Using Modified FDA Snapshot Algorithm | 24 weeks after start of HIV treatment | The percentage of participants with HIV-1 RNA ≥ 50 copies/mL 24 weeks after start of the F/TAF-based regimen were analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. |
| Percentage of Participants Experiencing Grades 1 Through 4 Adverse Events After Switch to E/C/F/TAF or F/R/TAF Throughout the Study and During Coadministeration With LDV/SOF Treatment | Up to 32 weeks plus 30 days | — |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States. The first participant was screened on 01 April 2016. The last study visit occurred on 29 September 2017.
Pre-assignment details
259 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| E/C/F/TAF + LDV/SOF Part 1: Participants received E/C/F/TAF 150/150/200/10 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to E/C/F/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study.
Part 2: Participants continued receiving E/C/F/TAF 150/150/200/10 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20). | 74 |
| F/R/TAF + LDV/SOF Part 1: Participants received F/R/TAF 200/25/25 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to F/R/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study.
Part 2: Participants continued receiving F/R/TAF 200/25/25 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20). | 74 |
| Total | 148 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Investigator's Discretion | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Participants Randomized but Not Treated | 2 | 0 |
| Overall Study | Withdrew Consent | 0 | 1 |
Baseline characteristics
| Characteristic | F/R/TAF + LDV/SOF | E/C/F/TAF + LDV/SOF | Total |
|---|---|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 9.9 | 51 years STANDARD_DEVIATION 9.5 | 51 years STANDARD_DEVIATION 9.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 13 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 59 Participants | 61 Participants | 120 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| HCV RNA | 6.3 log10 IU/mL STANDARD_DEVIATION 0.74 | 6.0 log10 IU/mL STANDARD_DEVIATION 1.07 | 6.2 log10 IU/mL STANDARD_DEVIATION 0.92 |
| HCV RNA Category < 800,000 IU/mL | 14 Participants | 25 Participants | 39 Participants |
| HCV RNA Category ≥ 800,000 IU/mL | 60 Participants | 49 Participants | 109 Participants |
| HIV-1 RNA Category < 50 copies/mL | 74 Participants | 73 Participants | 147 Participants |
| HIV-1 RNA Category ≥ 50 copies/mL | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 31 Participants | 30 Participants | 61 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 37 Participants | 41 Participants | 78 Participants |
| Sex: Female, Male Female | 22 Participants | 16 Participants | 38 Participants |
| Sex: Female, Male Male | 52 Participants | 58 Participants | 110 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 74 | 1 / 74 |
| other Total, other adverse events | 46 / 74 | 36 / 74 |
| serious Total, serious adverse events | 7 / 74 | 12 / 74 |
Outcome results
Primary
Percentage of Participants With HCV RNA < LLOQ at 12 Weeks After Discontinuation of LDV/SOF Treatment (SVR12)
Sustained Virologic Response (SVR12) was defined as HCV RNA \< the lower limit of quantitation (LLOQ) at 12 weeks after stopping LDV/SOF treatment.
Time frame: HCV Posttreatment Week 12
Population: HCV Full Analysis Set: participants who were randomized into the study and received at least 1 dose of HCV study drug, LDV/SOF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF + LDV/SOF | Percentage of Participants With HCV RNA < LLOQ at 12 Weeks After Discontinuation of LDV/SOF Treatment (SVR12) | 98.6 percentage of participants |
| F/R/TAF + LDV/SOF | Percentage of Participants With HCV RNA < LLOQ at 12 Weeks After Discontinuation of LDV/SOF Treatment (SVR12) | 95.8 percentage of participants |
p-value: 0.002Binomial test
p-value: 0.042Binomial test
Secondary
Percentage of Participants Experiencing Grades 1 Through 4 Adverse Events After Switch to E/C/F/TAF or F/R/TAF Throughout the Study and During Coadministeration With LDV/SOF Treatment
Time frame: Up to 32 weeks plus 30 days
Population: Safety Analysis Set (Whole Study): participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).~Safety Analysis Set (Part 2): participants who entered Part 2 of the study and received at least one dose of study drug LDV/SOF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF + LDV/SOF | Percentage of Participants Experiencing Grades 1 Through 4 Adverse Events After Switch to E/C/F/TAF or F/R/TAF Throughout the Study and During Coadministeration With LDV/SOF Treatment | 62.5 percentage of participants |
| F/R/TAF + LDV/SOF | Percentage of Participants Experiencing Grades 1 Through 4 Adverse Events After Switch to E/C/F/TAF or F/R/TAF Throughout the Study and During Coadministeration With LDV/SOF Treatment | 69.4 percentage of participants |
| E/C/F/TAF + LDV/SOF (Whole Study: Day 1 to Post-HCV Week 12) | Percentage of Participants Experiencing Grades 1 Through 4 Adverse Events After Switch to E/C/F/TAF or F/R/TAF Throughout the Study and During Coadministeration With LDV/SOF Treatment | 83.8 percentage of participants |
| F/R/TAF + LDV/SOF (Whole Study: Day 1 to Post-HCV to Week 12) | Percentage of Participants Experiencing Grades 1 Through 4 Adverse Events After Switch to E/C/F/TAF or F/R/TAF Throughout the Study and During Coadministeration With LDV/SOF Treatment | 79.7 percentage of participants |
Secondary
Percentage of Participants With HCV RNA < LLOQ at 4 Weeks After Discontinuation of LDV/SOF Treatment (SVR4)
SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping LDV/SOF treatment.
Time frame: HCV Posttreatment Week 4
Population: HCV Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF + LDV/SOF | Percentage of Participants With HCV RNA < LLOQ at 4 Weeks After Discontinuation of LDV/SOF Treatment (SVR4) | 98.6 percentage of participants |
| F/R/TAF + LDV/SOF | Percentage of Participants With HCV RNA < LLOQ at 4 Weeks After Discontinuation of LDV/SOF Treatment (SVR4) | 98.6 percentage of participants |
p-value: 0.002Binomial test
p-value: 0.002Binomial test
Secondary
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL (Virologic Failure) 24 Weeks After Start of the F/TAF-Based Regimen Using Modified FDA Snapshot Algorithm
The percentage of participants with HIV-1 RNA ≥ 50 copies/mL 24 weeks after start of the F/TAF-based regimen were analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time frame: 24 weeks after start of HIV treatment
Population: HIV Full Analysis Set: participants who were randomized into the study and received at least 1 dose of HIV study drug, E/C/F/TAF or F/R/TAF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF + LDV/SOF | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL (Virologic Failure) 24 Weeks After Start of the F/TAF-Based Regimen Using Modified FDA Snapshot Algorithm | 1.4 percentage of participants |
| F/R/TAF + LDV/SOF | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL (Virologic Failure) 24 Weeks After Start of the F/TAF-Based Regimen Using Modified FDA Snapshot Algorithm | 1.4 percentage of participants |
p-value: 195% CI: [-6.1, 6.1]Fisher exact test