Study to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) in Virologically-Suppressed HIV-1 Infected Adults Harboring the Archived Isolated NRTI Resistance Mutation M184V/M184I

NCT ID: NCT02616029

Last Updated: 2020-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-17
• Study Completion Date: 2019-07-11

Brief Summary

The primary objective of the study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) after switching from a stable regimen consisting of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) plus a third antiretroviral (ARV) agent in participants harboring the archived nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance mutation M184V and/or M184I in human immunodeficiency virus (HIV) -1 reverse transcriptase.

This is a two part study. If the rate of virologic failure in Part 1 is deemed acceptable, once the internal data monitoring committee officially completes the interim review, the study will continue to Part 2.

Conditions

HIV-1 Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: E/C/F/TAF

Participants with M184V and/or M184I mutations in reverse transcriptase and without any other NRTI resistance mutation switched from their current human immunodeficiency virus (HIV) treatment regimen consisting of FTC/TDF or ABC/3TC plus a third antiretroviral agent to E/C/F/TAF (150/150/200/10 mg) FDC tablet orally once daily for 48 weeks.

Allowed third agents include: lopinavir/ritonavir (LPV/r), atazanavir + ritonavir (ATV+RTV), atazanavir+cobicistat (ATV+COBI), darunavir + ritonavir (DRV+RTV), darunavir + cobicistat (DRV+COBI), fosamprenavir + ritonavir (FPV + RTV), saquinavir + ritonavir (SQV + RTV), atazanavir (ATV) (no booster) efavirenz (EFV), rilpivirine (RPV), nevirapine (NVP), etravirine (ETR), raltegravir (RAL) or dolutegravir (DTG).

Group Type: EXPERIMENTAL

E/C/F/TAF

Intervention Type: DRUG

150/150/200/10 mg FDC tablets administered orally once daily

Part 2: E/C/F/TAF

Participants with M184V and/or M184I mutations in reverse transcriptase and with or without 1 or 2 TAMs switched from their current HIV treatment regimen consisting of FTC/TDF or ABC/3TC plus a third antiretroviral agent to E/C/F/TAF (150/150/200/10 mg) FDC tablet orally once daily for 48 weeks.

Allowed third agents include: LPV/r, ATV+RTV, ATV+COBI, DRV+RTV, DRV+COBI, FPV + RTV, SQV + RTV, ATV (no booster) EFV, RPV, NVP, ETR, RAL or DTG.

Group Type: EXPERIMENTAL

E/C/F/TAF

Intervention Type: DRUG

150/150/200/10 mg FDC tablets administered orally once daily

Interventions

E/C/F/TAF

150/150/200/10 mg FDC tablets administered orally once daily

Intervention Type: DRUG

Other Intervention Names

Genvoya®

Eligibility Criteria

Inclusion Criteria

• Documented historical genotype report showing mutation M184V and/or M184I (mixtures are acceptable) in reverse transcriptase. Individuals must not have any primary integrase strand transfer inhibitor (INSTI) or primary protease inhibitor (PI) resistance mutations present on historical genotype; non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations are allowed.
• Proviral deoxyribonucleic acid (DNA) test must not have additional exclusion resistance mutations against PIs, NRTIs and INSTIs

• Part 1: Historical genotype report must show mutation M184V and/or M184I in reverse transcriptase WITHOUT any other NRTI resistance mutation (including thymidine analogue-associated mutations [TAMs] [TAMs are: M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E/N/R], K65R, K70E, T69 insertion, and Q151M mutation complex [A62V, V75I, F77L, F116Y, Q151M])
• Part 2 (after the interim efficacy review): Historical genotype report must show M184V and/or M184I in reverse transcriptase WITH or WITHOUT 1 or 2 TAMs. Evidence of K65R, K70E, T69 insertion and/or Q151M mutation complex will not be eligible
• Currently receiving an ARV regimen consisting of FTC/TDF or ABC/3TC in combination with one third ARV agent for ≥ 6 consecutive months preceding the screening visit
• Documented plasma HIV-1 ribonucleic acid (RNA) levels < 50 copies/mL for ≥ 6 months preceding the screening visit
• Plasma HIV-1 RNA levels < 50 copies/mL at screening visit
• Estimated glomerular filtration rate (GFR) ≥ 30 mL/min according to the Cockcroft-Gault formula for creatinine clearance
• A female individual is eligible to enter the study if it is confirmed that she is:

• not pregnant
• of non-childbearing potential
• stopped menstruating for ≥ 12 months
• of childbearing potential and agrees to utilize the protocol-specified method of contraception or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following discontinuation of study drugs
• Male individuals must agree to use the protocol-specified method(s) of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from screening throughout the study period and for 30 days following the last study drug dose

• Male individuals must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose

Exclusion Criteria

• Individuals will have no evidence of previous virologic failure on a PI/r or INSTI-based regimen (with or without resistance to either class of ARV). Individuals may have evidence of prior virologic failure on only an NNRTI plus 2 NRTI-based regimen
• Individuals on a current PI/r-based regimen will have no evidence of previous use of any approved or experimental integrase strand transfer inhibitor (INSTI) (for any length of time)
• Hepatitis C infection that would require therapy during the study
• Hepatitis B surface antigen (HBsAg) positive
• Individuals with clinical evidence of decompensated cirrhosis (eg, ascites, encephalopathy, variceal bleeding)
• Have an implanted defibrillator or pacemaker
• A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non invasive cutaneous squamous carcinoma. Individuals with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Day 1 and must not be anticipated to require systemic therapy during the study
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Midway Immunology & Research Center, LLC

Ft. Pierce, Florida, United States

Orlando Immunology Center

Orlando, Florida, United States

Triple O Research Institute PA

West Palm Beach, Florida, United States

Hopital Sainte Marguerite - Hospital

Marseille, , France

CHU de Nantes

Nantes, , France

CHU de Nice-l Archet

Nice, , France

CHR Orleans la Source

Orléans, , France

Hopital Saint Louis

Paris, , France

Hopital Necker les Enfants Malades

Paris, , France

CHU Tours Service de Médecine Internes et Maladies Infectieuses

Tours, , France

Universitatsklinikum Essen

Essen, , Germany

ICH Study Center- Dedicated Research

Hamburg, , Germany

Universitat Mainz

Mainz, , Germany

IRCCS A.O.U. San Martino

Genova, , Italy

Fondazione IRCCS San Raffaele del Monte Tabor

Milan, , Italy

ASST Fatebenefratelli Sacco - Ospedale Luigi Sacco

Milan, , Italy

Comprensorio Amedeo Di Savoia Birago Di Vische

Torino, , Italy

Hospital Universitari Germans Trias i Pujol

Badalona, , Spain

Hospital Clinic de Barcelona - Hospital

Barcelona, , Spain

Hospital Universitario 12 de Octubre - Hospital

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Countries

United States; France; Germany; Italy; Spain

References

Perez-Valero I, Llibre JM, Lazzarin A, di Perri G, Pulido F, Molina JM, Esser S, Margot N, Shao Y, Piontkowsky D, Das M, McNicholl IR, Haubrich R. A Phase 3b Open-Label Pilot Study to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) in Virologically-Suppressed HIV-1 Infected Adults Harboring the NRTI Resistance Mutation M184V/I (GS-US-292-1824): Week 24 Results [Poster PE13/20]. 17th European AIDS Conference (EACS), 6-9 November 2019, Basel, Switzerland.

Reference Type: BACKGROUND

Perez-Valero I, Llibre JM, Lazzarin A, di Perri G, Pulido F, Molina JM, Esser S, McNicholl IR, Lorgeoux RP, Margot N, Shao Y, Piontkowsky D, Das M, Haubrich R. A Phase 3b Open-Label Pilot Study to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single-Tablet Regimen in Virologically-Suppressed HIV-1 Infected Adults Harboring the NRTI Resistance Mutation M184V and/or M184I (GS-US-292-1824): Week 24 Results [Oral abstract]. 22nd International AIDS Conference, 23-27 July 2018, Amsterdam, The Netherlands.

Reference Type: BACKGROUND

Perez-Valero I, Llibre JM, Lazzarin A, di Perri G, Pulido F, Molina JM, Esser S, McNicholl IR, Lorgeoux RP, Margot N, Shao Y, Piontkowsky D, Das M, Haubrich R. A Phase 3b Open-Label Pilot Study to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen in Virologically-Suppressed HIV-1 Infected Adults Harboring the NRTI Resistance Mutation M184V and/or M184I (GS-US-292-1824): Week 12 Results [Poster]. XXVI International Workshop on HIV Drug Resistance and Treatment Strategies, 6-8 November 2017, Johannesburg, South Africa.

Reference Type: BACKGROUND

Perez-Valero I, Llibre JM, Castagna A, Pulido F, Molina JM, Esser S, Margot N, Shao Y, Temme L, Piontkowsky D, McNicholl IR, Haubrich R. Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation. J Acquir Immune Defic Syndr. 2021 Apr 1;86(4):490-495. doi: 10.1097/QAI.0000000000002595.

Reference Type: DERIVED

PMID: 33315694 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-002710-74

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-292-1824

Identifier Type: -

Identifier Source: org_study_id