Study to Evaluate Switching From a Regimen Consisting of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) Fixed Dose Combination (FDC) to Emtricitabine/Rilpivirine/Tenofovir Alafenamide (FTC/RPV/TAF) FDC in Virologically-Suppressed, HIV-1 Infected Adults

HIV-1 Infection Clinical Trial

Official title:

A Phase 3b, Randomized, Double-Blind Study to Evaluate Switching From a Regimen Consisting of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) Fixed Dose Combination (FDC) to Emtricitabine/Rilpivirine/ Tenofovir Alafenamide (FTC/RPV/TAF) FDC in Virologically-Suppressed, HIV-1 Infected Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02345226
• Other study ID #: GS-US-366-1160
• Secondary ID: 2014-004779-21
• Status: Completed
• Phase: Phase 3
• Start date: January 26, 2015
• Est. completion date: January 2, 2019

Study information

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

Clinical Trial Summary

The primary objective of this study is to evaluate the non-inferiority of switching to emtricitabine/rilpivirine/tenofovir alafenamide (FTC/RPV/TAF) fixed dose combination (FDC) as compared to continuing the non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen of efavirenz /FTC/tenofovir disoproxil fumarate (EFV/FTC/TDF) FDC in virologically-suppressed HIV-1 infected participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 881
• Est. completion date: January 2, 2019
• Est. primary completion date: June 29, 2016
• 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, which must be obtained prior to initiation of study procedures

• Currently receiving EFV/FTC/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. Unconfirmed virologic elevation of = 50 copies/mL after previously reaching viral suppression (transient detectable viremia, or "blip") and prior to screening is acceptable

• 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, or normal direct bilirubin

• Adequate hematologic function (absolute neutrophil count = 1,000/mm^3; platelets = 50,000/mm^3; hemoglobin = 8.5 g/dL)

• 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 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 the 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 protocol defined inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• FTC/RPV/TAF
200/25/25 mg FDC tablets administered orally once daily
• EFV/FTC/TDF Placebo
Tablets administered orally once daily
• EFV/FTC/TDF
600/200/300 mg FDC tablets administered orally once daily
• FTC/RPV/TAF Placebo
Tablets administered orally once daily

Locations

Country	Name	City	State
Belgium	CHU Saint-Pierre University Hospital	Brussels
Belgium	Cliniques Universitaires UCL Saint-Luc	Brussels
Canada	University of Alberta	Edmonton	Alberta
Canada	Clinique medicale l'Actuel	Montreal	Quebec
Canada	Clinique OPUS	Montreal	Quebec
Canada	McGill University Health Centre	Montreal	Quebec
Canada	Maple Leaf Research	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
Canada	Spectrum Health	Vancouver	British Columbia
Canada	Health Sciences Centre	Winnipeg	Manitoba
France	Hopital Bichat Claude Bernard	Paris
France	Hopital Saint Louis	Paris
France	Chu Tours	Tours
Germany	Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH (zibp)	Berlin
Germany	University of Bonn	Bonn
Germany	Center for HIV and Hepatogastroenterology	Duesseldorf
Germany	Universitätsklinikum Essen	Essen
Germany	Infektiologikum	Frankfurt
Germany	ICH Study Center Hamburg	Hamburg
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitat zu Koln	Koln
Germany	MUC Research GmbH	München
Puerto Rico	Clinical Research Puerto Rico Inc	San Juan
Puerto Rico	Hope Clinical Research	San Juan
Puerto Rico	University of Puerto Rico School of Medicine	San Juan
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitary de Bellvitge	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Switzerland	University Hospital Basel	Basel
Switzerland	Geneva University Hospital	Genève
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
United Kingdom	Barts & The London NHS Trust	London
United Kingdom	King's College Hospital	London
United Kingdom	Mortimer Market Centre	London
United Kingdom	The Royal Free Hampstead NHS Trust	London
United States	Upstate Infectious Diseases Associates	Albany	New York
United States	Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)	Annandale	Virginia
United States	AIDS Research Consortium of Atlanta	Atlanta	Georgia
United States	Atlanta ID Group	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Central Texas Clinical Research	Austin	Texas
United States	Be Well Medical Center	Berkley	Michigan
United States	AHF Research Center	Beverly Hills	California
United States	Pacific Oaks Medical Group	Beverly Hills	California
United States	Boston University Medical Center	Boston	Massachusetts
United States	Brigham and Women's	Boston	Massachusetts
United States	Jacobi Medical Center	Bronx	New York
United States	Montefiore Medical Center	Bronx	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Infectious Disease Consultants, PA	Charlotte	North Carolina
United States	The CORE Foundation	Chicago	Illinois
United States	The Ohio State University	Columbus	Ohio
United States	North Texas Infectious Diseases Consultants	Dallas	Texas
United States	Southwest Infectious Disease Clinical Research, Inc.	Dallas	Texas
United States	Trinity Health and Wellness Center/AIDS Arms, Inc.	Dallas	Texas
United States	Infectious Disease Specialists of Atlanta	Decatur	Georgia
United States	Apex Research Institute	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Gary Richmond, MD, PA, Inc.	Fort Lauderdale	Florida
United States	Therafirst Medical Centers	Fort Lauderdale	Florida
United States	Midway Immunology & Research Center, LLC	Fort Pierce	Florida
United States	AIDS Arms, Inc./Trinity Health & Wellness Center	Fort Worth	Texas
United States	MetroWest Medical Center	Framingham	Massachusetts
United States	The Brody School of Medicine	Greenville	North Carolina
United States	Gordon E. Crofoot, MD, PA	Houston	Texas
United States	Research Access Network	Houston	Texas
United States	Rosedale Infectious Diseases	Huntersville	North Carolina
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	Long Beach Education and Research Consultants	Long Beach	California
United States	DCOL Center for Clinical Research	Longview	Texas
United States	Kaiser Permanente	Los Angeles	California
United States	Southern California Men's Medical Group	Los Angeles	California
United States	Tarrant County ID Associates	Los Angeles	California
United States	Mercer University School of Medicine	Macon	Georgia
United States	North Shore University Hospital	Manhasset	New York
United States	AIDS Healthcare Foundation	Miami	Florida
United States	University of Miami	Miami	Florida
United States	AIDS Healthcare Foundation	Miami Beach	Florida
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University Medical Center/ New York Presbyterian	New York	New York
United States	Saint Michael's Medical Center	Newark	New Jersey
United States	World Health Clinicians' CIRCLE CARE Center	Norwalk	Connecticut
United States	Orlando Immunology Center	Orlando	Florida
United States	Infectious Diseases Associates of NW Florida, P.A.	Pensacola	Florida
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Maricopa Integrated Health System	Phoenix	Arizona
United States	Spectrum Medical Group	Phoenix	Arizona
United States	The Miriam Hospital	Providence	Rhode Island
United States	Kaiser Permanente	Sacramento	California
United States	University of California-UC Davis	Sacramento	California
United States	Southampton Healthcare, Inc.	Saint Louis	Missouri
United States	La Playa Medical Group and Clinical Research	San Diego	California
United States	Kaiser Permanente	San Francisco	California
United States	Optimus Medical	San Francisco	California
United States	Kaiser Permanente	San Leandro	California
United States	Southwest CARE Center	Santa Fe	New Mexico
United States	Chatham County Health Department	Savannah	Georgia
United States	Peter Shalit, MD	Seattle	Washington
United States	South Jersey Infectious Disease	Somers Point	New Jersey
United States	Premier Clinical Research	Spokane	Washington
United States	Baystate Infectious Diseases Clinical Research	Springfield	Massachusetts
United States	The Research Institute	Springfield	Massachusetts
United States	Hillsborough County Health Dept.	Tampa	Florida
United States	Infectious Disease Research Institute Inc.	Tampa	Florida
United States	St. Joseph's Comprehensive Research Institute	Tampa	Florida
United States	Los Angeles BioMedical Institute at Harbor-UCLA Medical Center	Torrance	California
United States	AIDS Research & Treatment Center of the Treasure Coast	Vero Beach	Florida
United States	Capital Medical Associates, P.C.	Washington	District of Columbia
United States	Medical Faculty Associates, Inc.	Washington	District of Columbia
United States	Whitman Walker Clinic	Washington	District of Columbia
United States	Triple O Research Institute, P.A.	West Palm Beach	Florida
United States	Rowan Tree Medical PA	Wilton Manors	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Puerto Rico,  Spain,  Switzerland,  United Kingdom, 

References & Publications (11)

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

DeJesus E, Ramgopal M, Crofoot G, Ruane P, LaMarca A, Mills A, Martorell CT, de Wet J, Stellbrink HJ, Molina JM, Post FA, Valero IP, Porter D, Liu Y, Cheng A, Quirk E, SenGupta D, Cao H. Switching from efavirenz, emtricitabine, and tenofovir disoproxil fu — View Citation

E DeJesus, M Ramgopal, G Crofoot, P Ruane, A LaMarca. J-M Molina et al. Efficacy and Safety of Switching to RPV/FTC/TAF in Older Adults. 8th International Workshop on HIV and Aging 2017 2-3 October, New York, New York.

Hagins D, Mills A, Martorell C, Walmsley S, Gallant J, Tebas P, et al. Efficacy and Safety of Switching to RPV/FTC/TAF in Women [Abstract 12]. 7th International Workshop on HIV & Women; 2017 11-12 February; Seattle, Washington.

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), emtr — View 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 [Poster 427]. Conference on Retroviruses and Opportunistic Infections (CROI) 2017 13-16 February; Seattle

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.

Molina JM, DeJesus E, Rijnders B, Post FAV, B., Stoeckle M, ThalmeA, et al. Efficacy and 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,

Orkin C, DeJesus E, Ramgopal M, Crofoot G, Ruane P, LaMarca A, et al. 48 Week Results from two studies: Switching to RPV/FTC/TAF from EFV/FTC/TDF (Study 1160) or RPV/FTC/TDF (Study 1216) [Presentation]. HIV Glasgow; 2016 23-26 October; Glasgow, United Kin

Porter DP, KulkarniR, Cao H, SenGupta D, and White KL. No Emergent Resistance in HIV-1 Virologically-Suppressed Subjects Who Switched to RPV/FTC/TAF [Poster 1381]. ID Week 2017 4-8 October; San Diego, California.

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 Suppresse

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US 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 patient'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 48 as Defined by the US 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 patient'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 Defined by the US 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 patient'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 96 as Defined by the US FDA-defined Snapshot	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a patient'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	Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.	Baseline; Week 48
Secondary	Percent Change From Baseline in Hip BMD at Week 96	Hip BMD was assessed by DXA scan.	Baseline; Week 96
Secondary	Percent Change From Baseline in Spine BMD at Week 48	Spine BMD was assessed by DXA scan.	Baseline; Week 48
Secondary	Percent Change From Baseline in Spine BMD at Week 96	Spine BMD was assessed by DXA scan.	Baseline; Week 96
Secondary	Change From Baseline in HIV Symptoms Index Score (HIVSI) at Week 48	The HIV Symptoms Index was a 20-item, self-reported measure that addressed presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Twenty HIV symptoms including Fatigue, Fever, Dizziness, Hand/Foot Pain, Memory Loss, Nausea, Diarrhea, Sadness, Nervous/anxious, Sleep Trouble, Skin Problems, Cough, Headache, Appetite Loss, Stomach Pain, Muscle/Joint Pain, Sex Problems, Change in Fat Deposits, Weight Loss, and Hair Loss were assessed. There were 5 possible responses (0 = I don't have this symptom; 1 = It doesn't bother me; 2 = It bothers me a little; 3 = It bothers me; and 4 = It bothers me a lot) for each HIV symptom. Total HIV Symptoms Index Score was derived from all 20 HIV symptoms by counting the number of bothersome symptoms. Total score would be missing if any of the individual items were missing.	Baseline; Week 48
Secondary	Change From Baseline in HIVSI Score at Week 96	The HIV Symptoms Index was a 20-item, self-reported measure that addressed presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Twenty HIV symptoms including Fatigue, Fever, Dizziness, Hand/Foot Pain, Memory Loss, Nausea, Diarrhea, Sadness, Nervous/anxious, Sleep Trouble, Skin Problems, Cough, Headache, Appetite Loss, Stomach Pain, Muscle/Joint Pain, Sex Problems, Change in Fat Deposits, Weight Loss, and Hair Loss were assessed. There were 5 possible responses (0 = I don't have this symptom; 1 = It doesn't bother me; 2 = It bothers me a little; 3 = It bothers me; and 4 = It bothers me a lot) for each HIV symptom. Total HIV Symptoms Index Score was derived from all 20 HIV symptoms by counting the number of bothersome symptoms. Total score would be missing if any of the individual items were missing.	Baseline; Week 96