Switch Study to Evaluate F/TAF in HIV-1 Infected Adults Who Are Virologically Suppressed on Regimens Containing ABC/3TC

NCT ID: NCT02469246

Last Updated: 2019-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 567 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-29
• Study Completion Date: 2019-03-13

Brief Summary

The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of switching abacavir/lamivudine (ABC/3TC) fixed-dose combination (FDC) tablets to emtricitabine/tenofovir alafenamide (F/TAF) FDC tablets versus maintaining ABC/3TC in human immunodeficiency virus type 1 (HIV-1) infected adults who are virologically suppressed on regimens containing ABC/3TC.

Conditions

HIV-1 Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

F/TAF (Double-Blind)

F/TAF + ABC/3TC placebo + allowed 3rd antiretroviral (ARV) agent for 96 weeks

After Week 96, participants will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments have been unblinded.

Group Type: EXPERIMENTAL

F/TAF

Intervention Type: DRUG

200/10 mg FDC tablet (with boosted 3rd ARV agents) or 200/25 mg FDC tablet (with unboosted 3rd ARV agents) administered orally once daily

ABC/3TC Placebo

Intervention Type: DRUG

Tablets administered orally once daily

3rd ARV agent

Intervention Type: DRUG

An allowed 3rd ARV agent of the participant's pre-existing regimen may include one of the following boosted ARV agents: ritonavir boosted lopinavir (LPV/r), atazanavir (ATV) + ritonavir (RTV), ATV + cobicistat (COBI) or ATV/COBI FDC, darunavir (DRV) + RTV, DRV+COBI or DRV/COBI FDC; or, one of the following unboosted ARV agents: efavirenz (EFV), rilpivirine (RPV), raltegravir (RAL), dolutegravir (DTG), maraviroc (MVC), or nevirapine (NVP).

ABC/3TC (Double-Blind)

ABC/3TC + F/TAF placebo + allowed 3rd ARV agent for 96 weeks

After Week 96, participants will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments have been unblinded.

Group Type: ACTIVE_COMPARATOR

ABC/3TC

Intervention Type: DRUG

600/300 mg FDC tablets administered orally once daily

F/TAF Placebo

Intervention Type: DRUG

Tablets administered orally once daily

3rd ARV agent

Intervention Type: DRUG

An allowed 3rd ARV agent of the participant's pre-existing regimen may include one of the following boosted ARV agents: ritonavir boosted lopinavir (LPV/r), atazanavir (ATV) + ritonavir (RTV), ATV + cobicistat (COBI) or ATV/COBI FDC, darunavir (DRV) + RTV, DRV+COBI or DRV/COBI FDC; or, one of the following unboosted ARV agents: efavirenz (EFV), rilpivirine (RPV), raltegravir (RAL), dolutegravir (DTG), maraviroc (MVC), or nevirapine (NVP).

Open-Label F/TAF

After the unblinding visit, in countries where F/TAF FDC is not commercially available, participants (except in certain countries such as the UK) will be given the option to receive open-label F/TAF (200/10 mg or 200/25 mg) FDC and attend study visits every 12 weeks until it becomes commercially available, or until Gilead terminates the study in that country.

Group Type: EXPERIMENTAL

F/TAF

Intervention Type: DRUG

200/10 mg FDC tablet (with boosted 3rd ARV agents) or 200/25 mg FDC tablet (with unboosted 3rd ARV agents) administered orally once daily

Interventions

F/TAF

200/10 mg FDC tablet (with boosted 3rd ARV agents) or 200/25 mg FDC tablet (with unboosted 3rd ARV agents) administered orally once daily

Intervention Type: DRUG

ABC/3TC

600/300 mg FDC tablets administered orally once daily

Intervention Type: DRUG

ABC/3TC Placebo

Tablets administered orally once daily

Intervention Type: DRUG

F/TAF Placebo

Tablets administered orally once daily

Intervention Type: DRUG

3rd ARV agent

An allowed 3rd ARV agent of the participant's pre-existing regimen may include one of the following boosted ARV agents: ritonavir boosted lopinavir (LPV/r), atazanavir (ATV) + ritonavir (RTV), ATV + cobicistat (COBI) or ATV/COBI FDC, darunavir (DRV) + RTV, DRV+COBI or DRV/COBI FDC; or, one of the following unboosted ARV agents: efavirenz (EFV), rilpivirine (RPV), raltegravir (RAL), dolutegravir (DTG), maraviroc (MVC), or nevirapine (NVP).

Intervention Type: DRUG

Other Intervention Names

Descovy®

Eligibility Criteria

Inclusion Criteria

• The ability to understand and sign a written informed consent form
• On antiretroviral regimen containing ABC/3TC FDC in combination with one 3rd agent for ≥ 6 consecutive months prior to screening
• Plasma HIV-1 RNA levels < 50 copies/mL for ≥ 6 months preceding the screening visit (measured at least twice using the same assay) and without experiencing two consecutive HIV-1 RNA above detectable levels after achieving a confirmed (two consecutive) HIV-1 RNA below detectable levels on the current regimen in the past year
• Plasma HIV-1 RNA should be < 50 copies/mL at the screening visit
• Normal ECG
• Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the Cockcroft Gault formula for creatinine clearance
• Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
• Adequate hematologic function
• Serum amylase ≤ 5 × ULN
• Females of childbearing potential and males must agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following the last dose of study drug

Exclusion Criteria

• A new AIDS-defining condition diagnosed within the 30 days prior to screening
• Hepatitis B surface antigen (HBsAg) positive
• Individuals experiencing decompensated cirrhosis
• Individuals receiving ongoing treatment with bisphosphonate to treat bone disease (eg, osteoporosis)
• Pregnant or lactating females
• Have an implanted defibrillator or pacemaker
• Current alcohol or substance use judged by the investigator to potentially interfere with study compliance
• 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.
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 Visit
• Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements
• Participation in any other clinical trial (including observational trials) without prior approval
• Medications excluded due to the potential for interaction with emtricitabine (FTC), TAF, ABC or 3TC

• 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

Spectrum Medical Group

Phoenix, Arizona, United States

Pacific Oaks Medical Group

Beverly Hills, California, United States

University of California San Diego (UCSD)

La Jolla, California, United States

Anthony Mills, MD, Inc.

Los Angeles, California, United States

Peter J. Ruane, MD, Inc.

Los Angeles, California, United States

Highland Hospital - Alameda Health System

Oakland, California, United States

La Playa Medical Group and Clinical Research

San Diego, California, United States

Capial Medical Associates

Washington D.C., District of Columbia, United States

Dupont Circle Physician's Group

Washington D.C., District of Columbia, United States

Whitman-Walker Health

Washington D.C., District of Columbia, United States

Gary J. Richmond,M.D.,P.A.

Fort Lauderdale, Florida, United States

Therafirst Medical Center

Fort Lauderdale, Florida, United States

Midway Immunology and Research Center

Ft. Pierce, Florida, United States

Orlando Immunology Center

Orlando, Florida, United States

Triple O Research Institute PA

West Palm Beach, Florida, United States

Atlanta ID Group

Atlanta, Georgia, United States

Howard Brown Health Center

Chicago, Illinois, United States

University of Louisville

Louisville, Kentucky, United States

LSU Health Sciences Center

New Orleans, Louisiana, United States

Be Well Medical Center

Berkley, Michigan, United States

Hennepin County Medical Center

Minneapolis, Minnesota, United States

The KC CARE Clinic

Kansas City, Missouri, United States

Southampton Healthcare, Inc.

St Louis, Missouri, United States

Saint Michael's Medical Center

Newark, New Jersey, United States

South Jersey Infectious Disease

Somers Point, New Jersey, United States

Southwest CARE Center

Santa Fe, New Mexico, United States

Montefiore Medical Center

The Bronx, New York, United States

Philadelphia FIGHT

Philadelphia, Pennsylvania, United States

Central Texas Clinical Research

Austin, Texas, United States

AIDS Arms, Inc

Dallas, Texas, United States

Tarrant County Infectious Disease Associates

Fort Worth, Texas, United States

Gordon E. Crofoot MD PA

Houston, Texas, United States

Therapeutic Concepts, PA

Houston, Texas, United States

Peter Shalit, MD

Seattle, Washington, United States

UZ Gent

Ghent, , Belgium

Centre Hospitalier Universitaire CHU Sart Tilman Liege

Liège, , Belgium

Clinique medicale l'Actuel

Montreal, , Canada

Maple Leaf Research

Toronto, , Canada

Spectrum Health

Vancouver, , Canada

Vancouver ID Research and Care Centre Society

Vancouver, , Canada

Hvidovre Hospital

Copenhagen, , Denmark

CHU - Groupe Saint-Andre

Bordeaux, , France

CHU de Bordeaux

Bordeaux, , France

C.H.U. de Nantes

Nantes, , France

CHR Orleans la Source

Orléans, , France

Chu Tours

Tours, , France

ICH Study Center Hamburg

Bielefeld, , Germany

Medizinische Universitatsklinik

Bonn, , Germany

Klinikum der Universitaet Koln

Cologne, , Germany

Universitatsklinikum Essen

Essen, , Germany

Johann Wolfgang Goethe-University Hospital

Frankfurt, , Germany

ifi-Studien und Projekte GmbH an der Asklepiosklinik St. Georg

Hamburg, , Germany

Universitatsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Universitätsklinikum München

Munich, , Germany

Mater Misericordiae University Hospital

Dublin, , Ireland

Saint James's Hospital

Dublin, , Ireland

University of Brescia

Brescia, , Italy

Azienda Ospedaliera Luigi Sacco

Milan, , Italy

Fondazione IRCCS San Raffaele del Monte Tabor

Milan, , Italy

Azienda Ospedaliero Universitaria Policlinico di Modena

Modena, , Italy

Istituto Nazionale Malattie Infettive Lazzaro Spallanzani I.R.C.C.S.

Roma, , Italy

Ospedale Amedeo di Savoia - Specializzato Malattie infettive

Torino, , Italy

Clinical Research Puerto Rico

San Juan, , Puerto Rico

Hope Clinical Research Inc

San Juan, , Puerto Rico

Bonaventura

Badalona, , Spain

Hospital Universitari de Bellvitge

Barcelona, , Spain

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital Clínico Universitario San Carlos

Madrid, , Spain

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Hospital Costa Del Sol

Málaga, , Spain

Karolinska University Hospital

Stockholm, , Sweden

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Barts Health NHS Trust

London, , United Kingdom

Chelsea and Westminster Hospital

London, , United Kingdom

Imperial College

London, , United Kingdom

Kings College Hospital NHS Trust

London, , United Kingdom

Lewisham and Greenwich NHS Trust

London, , United Kingdom

Royal Free Hospital

London, , United Kingdom

St. George's Hospital

London, , United Kingdom

Manchester Centre for Sexual Health

Manchester, , United Kingdom

Countries

United States; Belgium; Canada; Denmark; France; Germany; Ireland; Italy; Puerto Rico; Spain; Sweden; United Kingdom

References

Winston A, Post FA, DeJesus E, Podzamczer D, Di Perri G, Estrada V, Raffi F, Ruane P, Peyrani P, Crofoot G, Mallon PWG, Castelli F, Yan M, Cox S, Das M, Cheng A, Rhee MS. Tenofovir alafenamide plus emtricitabine versus abacavir plus lamivudine for treatment of virologically suppressed HIV-1-infected adults: a randomised, double-blind, active-controlled, non-inferiority phase 3 trial. Lancet HIV. 2018 Apr;5(4):e162-e171. doi: 10.1016/S2352-3018(18)30010-9. Epub 2018 Feb 20.

Reference Type: RESULT

PMID: 29475804 (View on PubMed)

Gupta SK, Post FA, Arribas JR, Eron JJ Jr, Wohl DA, Clarke AE, Sax PE, Stellbrink HJ, Esser S, Pozniak AL, Podzamczer D, Waters L, Orkin C, Rockstroh JK, Mudrikova T, Negredo E, Elion RA, Guo S, Zhong L, Carter C, Martin H, Brainard D, SenGupta D, Das M. Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: a pooled analysis of 26 clinical trials. AIDS. 2019 Jul 15;33(9):1455-1465. doi: 10.1097/QAD.0000000000002223.

Reference Type: RESULT

PMID: 30932951 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Week 48

View Document

Document Type: Statistical Analysis Plan: Final Analysis

View Document

Other Identifiers

2015-000871-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-311-1717

Identifier Type: -

Identifier Source: org_study_id