Clinical trial NCT02345252: Switch Study to Evaluate the Safety and Efficacy of Emtricitabine/Rilpivirine/Tenofovir Alafenamide (FTC/RPV/TAF) Fixed Dose Combination (FDC) in HIV-1 Positive Adults Who Are Virologically Suppressed on Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (FTC/RPV/TDF)
Official title: A Phase 3b, Randomized, Double-Blind Switch Study to Evaluate the Safety and Efficacy of Emtricitabine/Rilpivirine/Tenofovir Alafenamide (FTC/RPV/TAF) Fixed Dose Combination (FDC) in HIV-1 Positive Subjects Who Are Virologically Suppressed on Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (FTC/RPV/TDF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
Keywords: HIV
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-01-26
Enrollment: 632
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the noninferiority of switching to emtricitabine/rilpivirine /tenofovir alafenamide (FTC/RPV/TAF) fixed-dose combination (FDC) as compared to continuing FTC/RPV/tenofovir disoproxil fumarate (TDF) FDC (FTC/RPV/TDF) in virologically suppressed HIV-1 infected participants.


Eligibility criteria: Key Inclusion Criteria:

* The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* Currently receiving FTC/RPV/TDF FDC for ≥ 6 consecutive months preceding the screening visit
* 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 of HIV-1 RNA ≥ 50 copies/mL followed by resuppression, are allowed
* Have no documented resistance to any of the study agents at any time in the past
* HIV-1 RNA \< 50 copies/mL at the screening visit
* Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 mg/dL (≤ 26 μmol/L), or normal direct bilirubin
* Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm\^3 (1.00 GI/L); platelets ≥ 50,000/mm\^3 (50 GI/L); hemoglobin ≥ 8.5 g/dL (85 g/L))
* Serum amylase ≤ 5 × ULN (individuals with serum amylase \> 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)
* Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
* Adequate renal function: Estimated glomerular filtration rate ≥ 50 mL/min (1.17 mL/sec) according to the Cockcroft-Gault formula

Key Exclusion Criteria:

* Hepatitis B surface antigen (HBsAg) positive
* Hepatitis C antibody positive with detectable hepatitis C virus (HCV) RNA (individuals who have HCV antibody but no detectable HCV RNA are eligible to enroll)
* Individuals experiencing or with a medical history of decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
* Females who are breastfeeding
* Positive serum pregnancy test
* Current alcohol or substance use judged by the Investigator to potentially interfere with individual's 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. Individuals with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Baseline/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 Baseline/Day 1
* 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 from the sponsor is prohibited while participating in this trial
* Individuals receiving ongoing therapy with any of the disallowed medications listed in the protocol, including drugs not to be used with FTC, RPV and/or TAF; or individuals with any known allergies to the excipients of FTC/RPV/TAF

Note: Other Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 48
measure: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 96
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 96
measure: Change From Baseline in CD4+ Cell Count at Week 48
timeFrame: Baseline; Week 48
measure: Change From Baseline in CD4+ Cell Count at Week 96
timeFrame: Baseline; Week 96
measure: Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
timeFrame: Baseline; Week 48
measure: Percent Change From Baseline in Hip BMD at Week 96
timeFrame: Baseline; Week 96
measure: Percent Change From Baseline in Spine BMD at Week 48
timeFrame: Baseline; Week 48
measure: Percent Change From Baseline in Spine BMD at Week 96
timeFrame: Baseline; Week 96
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham (UAB)
state: Alabama
city: Phoenix
country: United States
facility: Spectrum Medical Group
state: Arizona
city: Beverly Hills
country: United States
facility: AHF Research Center
state: California
city: Beverly Hills
country: United States
facility: Pacific Oaks Medical Group
state: California
city: Long Beach
country: United States
facility: Long Beach Education and Research Consultants
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: Los Angeles
country: United States
facility: Southern California Men's Medical Group
state: California
city: Los Angeles
country: United States
facility: Tarrant County ID Associates
state: California
city: Oakland
country: United States
facility: Alameda County Medical Center
state: California
city: Palm Springs
country: United States
facility: Desert Medical Group Inc., dba Desert Oasis Healthcare Medical Group
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente
state: California
city: Sacramento
country: United States
facility: University of California-UC Davis
state: California
city: San Diego
country: United States
facility: La Playa Medical Group and Clinical Research
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente
state: California
city: San Francisco
country: United States
facility: Optimus Medical
state: California
city: San Leandro
country: United States
facility: Kaiser Permanente
state: California
city: Torrance
country: United States
facility: Los Angeles BioMedical Institute at Harbor-UCLA Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Denver
country: United States
facility: Apex Research Institute
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Norwalk
country: United States
facility: World Health Clinicians' CIRCLE CARE Center
state: Connecticut
city: Washington
country: United States
facility: Capital Medical Associates, P.C.
state: District of Columbia
city: Washington
country: United States
facility: Dupont Circle Physicians Group
state: District of Columbia
city: Washington
country: United States
facility: Medical Faculty Associates
state: District of Columbia
city: Washington
country: United States
facility: Whitman Walker Clinic
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Gary Richmond, MD, PA, Inc.
state: Florida
city: Fort Lauderdale
country: United States
facility: Therafirst Medical Centers
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology & Research Center, LLC
state: Florida
city: Miami Beach
country: United States
facility: AIDS Healthcare Foundation
state: Florida
city: Miami
country: United States
facility: AIDS Healthcare Foundation
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Pensacola
country: United States
facility: Infectious Diseases Associates of NW Florida, P.A.
state: Florida
city: Tampa
country: United States
facility: Hillsborough County Health Dept.
state: Florida
city: Tampa
country: United States
facility: Infectious Disease Research Institute Inc.
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Comprehensive Research Institute
state: Florida
city: Vero Beach
country: United States
facility: AIDS Research & Treatment Center of the Treasure Coast
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A.
state: Florida
city: Wilton Manors
country: United States
facility: Rowan Tree Medical PA
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Atlanta ID Group
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta
state: Georgia
city: Savannah
country: United States
facility: Chatham County Health Department
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Boston
country: United States
facility: Brigham and Women's
state: Massachusetts
city: Boston
country: United States
facility: Community Research Initiative
state: Massachusetts
city: Framingham
country: United States
facility: MetroWest Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Infectious Diseases Clinical Research
state: Massachusetts
city: Springfield
country: United States
facility: The Research Institute
state: Massachusetts
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Saint Louis
country: United States
facility: Southampton Healthcare, Inc.
state: Missouri
city: Neptune
country: United States
facility: Jersey Shore Medical Center
state: New Jersey
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: Somers Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Santa Fe
country: United States
facility: Southwest CARE Center
state: New Mexico
city: Albany
country: United States
facility: Upstate Infectious Diseases Associates
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center--Myers Park Infectious Disease Clinic
state: North Carolina
city: Huntersville
country: United States
facility: Rosedale Infectious Diseases
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants
state: Texas
city: Dallas
country: United States
facility: Trinity Health and Wellness Center/AIDS Arms, Inc.
state: Texas
city: Fort Worth
country: United States
facility: AIDS Arms, Inc./Trinity Health & Wellness Center
state: Texas
city: Houston
country: United States
facility: Gordon E. Crofoot, MD, PA
state: Texas
city: Houston
country: United States
facility: Research Access Network
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: Annandale
country: United States
facility: Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)
state: Virginia
city: Seattle
country: United States
facility: Peter Shalit, MD
state: Washington
city: Spokane
country: United States
facility: Premier Clinical Research
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Brussels
country: Belgium
facility: CHU Saint-Pierre University Hospital
city: Brussels
country: Belgium
facility: Cliniques Universitaires UCL Saint-Luc
city: Ghent
country: Belgium
facility: University Hospital Gent
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: Spectrum Health
state: British Columbia
city: Toronto
country: Canada
facility: Maple Leaf Research
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montreal
country: Canada
facility: Clinique medicale l'Actuel
state: Quebec
city: Montreal
country: Canada
facility: Clinique OPUS
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Montpellier
country: France
facility: Hôpital Gui de Chauliac - Service Maladies Infectieuses et Tropicales
city: Berlin
country: Germany
facility: Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH (zibp)
city: Bonn
country: Germany
facility: University of Bonn
city: Düsseldorf
country: Germany
facility: Center for HIV and Hepatogastroenterology
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt
country: Germany
facility: Infektiologikum
city: Hamburg
country: Germany
facility: Asklepios Klinik
city: Hamburg
country: Germany
facility: ICH Study Center Hamburg
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf
city: Koln
country: Germany
facility: Universitat zu Koln
city: München
country: Germany
facility: MUC Research GmbH
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Milano
country: Italy
facility: Fondazione IRCCS San Raffaele del Monte Tabor
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico Inc
city: San Juan
country: Puerto Rico
facility: Hope Clinical Research
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitary de Bellvitge
city: Madrid
country: Spain
facility: Hospital Clínico Universitario San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Stockholm
country: Sweden
facility: Karolinska Institutet
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Genève
country: Switzerland
facility: Geneva University Hospital
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow
city: London
country: United Kingdom
facility: Barts & The London NHS Trust
city: London
country: United Kingdom
facility: Chelsea & Westminster Hospital
city: London
country: United Kingdom
facility: Mortimer Market Centre
city: London
country: United Kingdom
facility: The Royal Free Hampstead NHS Trust
city: Manchester
country: United Kingdom
facility: The Hathersage Integrated Contraception, Sexual Health and HIV Service
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Hagins D, Orkin C, Daar ES, Mills A, Brinson C, DeJesus E, Post FA, Morales-Ramirez J, Thompson M, Osiyemi O, Rashbaum B, Stellbrink HJ, Martorell C, Liu H, Liu YP, Porter D, Collins SE, SenGupta D, Das M. Switching to coformulated rilpivirine (RPV), emtricitabine (FTC) and tenofovir alafenamide from either RPV, FTC and tenofovir disoproxil fumarate (TDF) or efavirenz, FTC and TDF: 96-week results from two randomized clinical trials. HIV Med. 2018 Nov;19(10):724-733. doi: 10.1111/hiv.12664. Epub 2018 Aug 12.
citation: Mills A, Brinson C, Martorell C, Crofoot G, Daar E, Osiyemi O, et al. Switching to RPV/FTC/TAF from RPV/FTC/TDF or EFV/FTC/TDF: Week 96 Results. Conference on Retroviruses and Opportunistic Infections,Boston. March 4-7, 2018, Abstract 504.
citation: Arribas JR, Rockstroh J, Post, Yazdanpanah Y, Cavassini, DeJesus E, et al. Bone and renal safety of switching to rilpivirine/emtricitabine/tenofovir alafenamide (RPV/FTC/TAF) from single-tablet regimens (STRs) containing efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) or rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF): Week48 subgroup analysis in patients at risk of or with comorbidities. Abstract accepted for presentation atthe 16th European AIDS Conference, 2017 25-27 October Milan, Italy.
citation: Porter DP, Kulkarni R, Cao H, SenGupta D, White KL. No Emergent Resistance in HIV-1 Virologically-Suppressed Subjects Who Switched to RPV/FTC/TAF [Poster1381]. ID Week™ (Infectious Diseases Society of America) 2017 4-8 October; San Diego, CA.
citation: Wohl D, Kulkarni R, Garner W, White KL, Porter DL. Viral Blips Were Infrequent in HIV1-Infected Virologically-Suppressed Adults Treated with Tenofovir Alafenamide or Tenofovir DF Rilpivirine-Containing Regimens [Poster1384]. ID Week™ (Infectious Diseases Society of America) 2017 4-8 October; San Diego, CA.
citation: DeJesus E, Ramgopal M, Crofoot G, Ruane P, LaMarca A, Molina J-M, et al. Efficacy and Safety of Switching to RPV/FTC/TAF in Older Adults. 8th International Workshopon HIV and Aging 2017 2-3 October, New York, New York.
citation: Molina JM, DeJesus E, Rijnders B, Post FAV, B., Stoeckle M, Thalme A, et al. Efficacy and Odefsey® StudyGS-US-366-1216Final Synoptic Clinical Study Report Final CONFIDENTIAL Page4 30July2019 Safety of Switching From RPV/FTC/TDF or EFV/FTC/TDF to RPV/FTC/TAF in Black Adults [Presentation MOPEB0291]. 9th IAS Conference on HIV Science 2017 23-26 July Paris, France.
citation: Rockstroh J, Orkin C, Yazdanpanah Y, Di Perri GDS, P. E., Arribas JR, Brinkman K, et al. Switching From TDF to TAF Improves Bone and Renal Safety Independent of Age, Sex, Race, or 3rd Agent: Results From Pooled Analysis (N=3816) of Virologically Suppressed HIV-1 Infected Adults [Presentation MOPEB0289]. 9th IAS Conference on HIV Science;2017 23-26July Paris, France.
citation: Orkin C, DeJesus E, Ramgopal M, Crofoot G, Ruane P, LaMarca A, Mills A, Vandercam B, de Wet J, Rockstroh J, Lazzarin A, Rijnders B, Podzamczer D, Thalme A, Stoeckle M, Porter D, Liu HC, Cheng A, Quirk E, SenGupta D, Cao H. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: a randomised, double-blind, multicentre, phase 3b, non-inferiority study. Lancet HIV. 2017 May;4(5):e195-e204. doi: 10.1016/S2352-3018(17)30031-0. Epub 2017 Mar 2.
citation: Majeed SR, Shao Y, Garner W, Scott J, Pérez-Ruixo C, SenGupta D, et al. Evaluation of RPV/FTC/TAF Exposure-Efficacy and Exposure-Safety Relationships [Poster427]. Conference on Retroviruses and Opportunistic Infections (CROI) 2017 13-16 February; Seattle, WA.
citation: Hagins D, Mills A, Martorell C, Walmsley S, Gallant J, Tebas P, et al. Efficacy and Safety of Switching toRPV/FTC/TAF in Women [Abstract12]. 7th International Workshop on HIV & Women; 2017 11-12 February; Seattle, Washington.
citation: Orkin C, DeJesus E, Ramgopal M, Crofoot G, Ruane P, LaMarca A, et al. 48Week Results from two studies: Switching to RPV/FTC/TAF from EFV/FTC/TDF (Study1160) or RPV/FTC/TDF (Study1216) [Presentation]. HIV Glasgow; 2016 23-26 October; Glasgow, United Kingdom.