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

HIV-1 Infection Clinical Trial

Official title:

A Phase 3b, Randomized, Double-Blind, Switch Study to Evaluate F/TAF in HIV-1 Infected Subjects Who Are Virologically Suppressed on Regimens Containing ABC/3TC

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02469246
• Other study ID #: GS-US-311-1717
• Secondary ID: 2015-000871-28
• Status: Completed
• Phase: Phase 3
• Start date: June 29, 2015
• Est. completion date: March 13, 2019

Study information

• Verified date: October 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 567
• Est. completion date: March 13, 2019
• Est. primary completion date: December 11, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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

Key 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• 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
• ABC/3TC
600/300 mg FDC tablets administered orally once daily
• ABC/3TC Placebo
Tablets administered orally once daily
• F/TAF Placebo
Tablets administered orally once daily
• 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).

Locations

Country	Name	City	State
Belgium	UZ Gent	Ghent
Belgium	Centre Hospitalier Universitaire CHU Sart Tilman Liege	Liege
Canada	Clinique medicale l'Actuel	Montreal
Canada	Maple Leaf Research	Toronto
Canada	Spectrum Health	Vancouver
Canada	Vancouver ID Research and Care Centre Society	Vancouver
Denmark	Hvidovre Hospital	Copenhagen
France	CHU - Groupe Saint-Andre	Bordeaux
France	CHU de Bordeaux	Bordeaux
France	C.H.U. de Nantes	Nantes
France	CHR Orleans la Source	Orleans
France	Chu Tours	Tours
Germany	ICH Study Center Hamburg	Bielefeld
Germany	Medizinische Universitatsklinik	Bonn
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	Klinikum der Universitaet Koln	Koln
Germany	Universitätsklinikum München	Munich
Ireland	Saint James's Hospital	Dublin
Ireland	Mater Misericordiae University Hospital	Dublin 7
Italy	University of Brescia	Brescia
Italy	Azienda Ospedaliera Luigi Sacco	Milano
Italy	Fondazione IRCCS San Raffaele del Monte Tabor	Milano
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
Puerto Rico	Clinical Research Puerto Rico	San Juan
Puerto Rico	Hope Clinical Research Inc	San Juan
Spain	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	Malaga
Sweden	Karolinska University Hospital	Stockholm
United Kingdom	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 States	Atlanta ID Group	Atlanta	Georgia
United States	Central Texas Clinical Research	Austin	Texas
United States	Be Well Medical Center	Berkley	Michigan
United States	Pacific Oaks Medical Group	Beverly Hills	California
United States	Montefiore Medical Center	Bronx	New York
United States	Howard Brown Health Center	Chicago	Illinois
United States	AIDS Arms, Inc	Dallas	Texas
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	Fort Pierce	Florida
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	The KC CARE Clinic	Kansas City	Missouri
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	University of Louisville	Louisville	Kentucky
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	LSU Health Sciences Center	New Orleans	Louisiana
United States	Saint Michael's Medical Center	Newark	New Jersey
United States	Highland Hospital - Alameda Health System	Oakland	California
United States	Orlando Immunology Center	Orlando	Florida
United States	Philadelphia FIGHT	Philadelphia	Pennsylvania
United States	Spectrum Medical Group	Phoenix	Arizona
United States	Southampton Healthcare, Inc.	Saint Louis	Missouri
United States	La Playa Medical Group and Clinical Research	San Diego	California
United States	Southwest CARE Center	Santa Fe	New Mexico
United States	Peter Shalit, MD	Seattle	Washington
United States	South Jersey Infectious Disease	Somers Point	New Jersey
United States	Capial Medical Associates	Washington	District of Columbia
United States	Dupont Circle Physician's Group	Washington	District of Columbia
United States	Whitman-Walker Health	Washington	District of Columbia
United States	Triple O Research Institute PA	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

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

References & Publications (2)

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. — View Citation

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 treatme — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 was 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.	Week 48
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 96 was 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.	Week 96
Secondary	Percentage of Participants With HIV-1 RNA = 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm	The percentage of participants with HIV-1 RNA = 50 copies/mL at Week 48 was 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.	Week 48
Secondary	Percentage of Participants With HIV-1 RNA = 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm	The percentage of participants with HIV-1 RNA = 50 copies/mL at Week 96 was 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.	Week 96
Secondary	Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 48 was 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.	Week 48
Secondary	Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 96 was 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.	Week 96
Secondary	Change From Baseline in CD4 Cell Count at Week 48		Baseline; Week 48
Secondary	Change From Baseline in CD4 Cell Count at Week 96		Baseline; Week 96
Secondary	Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48		Baseline; Week 48
Secondary	Percent Change From Baseline in Hip BMD at Week 96		Baseline; Week 96
Secondary	Percent Change From Baseline in Spine BMD at Week 48		Baseline; Week 48
Secondary	Percent Change From Baseline in Spine BMD at Week 96		Baseline; Week 96