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 (Co-STARs)

Gilead Sciences

Status and phase: Completed; Phase 3

Conditions: HIV-1 Infection; HCV Infection

Treatments: Drug: LDV/SOF; Drug: E/C/F/TAF; Drug: F/R/TAF

Study type: Interventional

Funder types: Industry

Identifiers

NCT02707601

GS-US-366-1992

2014-004545-27 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 150 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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150 participants in 2 patient groups

E/C/F/TAF + LDV/SOF

Experimental group

Description:

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.

Treatment:

Drug: E/C/F/TAF

Drug: LDV/SOF

F/R/TAF + LDV/SOF

Experimental group

Description:

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.

Treatment:

Drug: F/R/TAF

Drug: LDV/SOF