Efficacy, Safety, and Tolerability of Ledipasvir/Sofosbuvir (LDV/SOF) Treatment for HIV/HCV Co-infected Participants Who Switch to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) or Emtricitabine/Rilpivirine/Tenofovir Alafenamide (F/R/TAF) Prior to LDV/SOF HCV Treatment

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3b Randomized, Open-label, Controlled Study of the Efficacy, Safety and Tolerability of 12 Weeks of Ledipasvir/Sofosbuvir (LDV/SOF) Treatment for HIV/HCV Co-infected Subjects Who Switch to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) or Emtricitabine/Rilpivirine/Tenofovir Alafenamide (F/R/TAF) Prior to LDV/SOF HCV Treatment, the HIV/HCV Co-STARs Study (Co-infection Treatment With Single Tablet Antiviral Regimens)

Conditions
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HIV-1 Infection, HCV Infection

Intervention / Treatment
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* Drug: E/C/F/TAF
* Drug: F/R/TAF
* Drug: LDV/SOF


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E/C/F/TAF + LDV/SOF<br>Part 1: Participants will switch from 2 nucleoside reverse transcriptase inhibitors (NRTI) plus a third agent to E/C/F/TAF. Part 2: After 8 weeks of E/C/F/TAF treatment, the participants maintaining HIV-1 RNA < 50 copies/mL will start receiving LDV/SOF for 12 weeks and continue their HIV treatment until the end of the study. | Drug: E/C/F/TAF<br>* 150/150/200/10 mg fixed dose combination (FDC) tablet administered orally once daily<br>* Other names: Genvoya®;Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: F/R/TAF + LDV/SOF<br>Part 1: Participants will switch from 2 NRTI plus a third agent to F/R/TAF. Part 2: After 8 weeks of F/R/TAF treatment, the participants maintaining HIV-1 RNA < 50 copies/mL will start receiving LDV/SOF for 12 weeks and continue their HIV treatment until the end of the study. | Drug: F/R/TAF<br>* 200/25/25 mg FDC tablet administered orally once daily<br>* Other names: Odefsey®;Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | HCV Posttreatment Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | HCV Posttreatment Week 4 | 
| 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. | 24 weeks after start of HIV treatment | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, HCV, Antiretroviral therapy, HCV direct acting antiviral(s) (DAA)