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

NCT02616029 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-292-18242015-002710-74
• Study Type: interventional
• Target: 66
• Locations: 5 countries
• Sites: 21

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 12 as Defined by Pure Virologic Response (PVR)

  The percentage of participants with PVR for HIV-1 RNA cutoff at 50 copies/mL at Week 12 was summarized. PVR was the percentage of participants who did not have a confirmed virologic rebound. Virologic rebound was defined as 2 consecutive HIV-1 RNA values ≥ 50 copies/mL or the last available HIV-1 RNA value ≥ 50 copies/mL during the study followed by premature discontinuation from the study.

  Week 12

Secondary Outcomes (21)

• Percentage of Participants With Emergence of New Mutations in HIV-1 Reverse Transcriptase and Integrase

  Day 1 up to 48 weeks

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using PVR

  Week 24

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using PVR

  Week 48

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 Using the FDA Snapshot Analysis

  Week 12

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using the FDA Snapshot Analysis

  Week 24

Study Arms (2)

Part 1: E/C/F/TAF

EXPERIMENTAL

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).

Drug: E/C/F/TAF

Part 2: E/C/F/TAF

EXPERIMENTAL

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.

Drug: E/C/F/TAF

Interventions

E/C/F/TAF DRUG

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

Also known as: Genvoya®

Part 1: E/C/F/TAF; Part 2: E/C/F/TAF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (21)

Midway Immunology & Research Center, LLC

Ft. Pierce, Florida, 34982, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

Triple O Research Institute PA

West Palm Beach, Florida, 33407, United States

Location

Hopital Sainte Marguerite - Hospital

Marseille, 13009, France

Location

CHU de Nantes

Nantes, 44093, France

Location

CHU de Nice-l Archet

Nice, 06202, France

Location

CHR Orleans la Source

Orléans, 45000, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Hopital Necker les Enfants Malades

Paris, 75015, France

Location

CHU Tours Service de Médecine Internes et Maladies Infectieuses

Tours, 37044, France

Location

Universitatsklinikum Essen

Essen, 45147, Germany

Location

ICH Study Center- Dedicated Research

Hamburg, 20146, Germany

Location

Universitat Mainz

Mainz, 55131, Germany

Location

IRCCS A.O.U. San Martino

Genova, 16132, Italy

Location

Fondazione IRCCS San Raffaele del Monte Tabor

Milan, 20132, Italy

Location

ASST Fatebenefratelli Sacco - Ospedale Luigi Sacco

Milan, 20157, Italy

Location

Comprensorio Amedeo Di Savoia Birago Di Vische

Torino, 10149, Italy

Location

Hospital Universitari Germans Trias i Pujol

Badalona, 08916, Spain

Location

Hospital Clinic de Barcelona - Hospital

Barcelona, 08036, Spain

Location

Hospital Universitario 12 de Octubre - Hospital

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Related Publications (4)

• 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.

  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.

  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.

  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.

  PMID: 33315694 DERIVED

MeSH Terms

Interventions

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Cobicistat; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Tenofovir; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2015
• First Posted: November 26, 2015
• Study Start: December 17, 2015
• Primary Completion: October 11, 2018
• Study Completion: July 11, 2019
• Last Updated: July 23, 2020
• Results First Posted: November 4, 2019

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

FR (7); ES (4); IT (4); US (3); DE (3)