HIV-1 Infection Clinical Trial
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)
| Verified date | December 2019 |
| Source | Gilead Sciences |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 632 |
| Est. completion date | January 9, 2019 |
| Est. primary completion date | June 22, 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 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. |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | CHU Saint-Pierre University Hospital | Brussels | |
| Belgium | Cliniques Universitaires UCL Saint-Luc | Brussels | |
| Belgium | University Hospital Gent | Ghent | |
| 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 |
| France | Hôpital Gui de Chauliac - Service Maladies Infectieuses et Tropicales | Montpellier | |
| Germany | Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH (zibp) | Berlin | |
| Germany | University of Bonn | Bonn | |
| Germany | Center for HIV and Hepatogastroenterology | Düsseldorf | |
| Germany | Universitätsklinikum Essen | Essen | |
| Germany | Infektiologikum | Frankfurt | |
| Germany | Asklepios Klinik | Hamburg | |
| Germany | ICH Study Center Hamburg | Hamburg | |
| Germany | Universitatsklinikum Hamburg-Eppendorf | Hamburg | |
| Germany | Universitat zu Koln | Koln | |
| Germany | MUC Research GmbH | München | |
| Italy | Azienda Ospedaliera Papa Giovanni XXIII | Bergamo | |
| Italy | Fondazione IRCCS San Raffaele del Monte Tabor | Milano | |
| Netherlands | Erasmus MC | Rotterdam | |
| Puerto Rico | Clinical Research Puerto Rico Inc | San Juan | |
| Puerto Rico | Hope Clinical Research | San Juan | |
| Spain | Hospital General Universitario de Alicante | Alicante | |
| Spain | Hospital Germans Trias i Pujol | Badalona | |
| Spain | Hospital del Mar | Barcelona | |
| Spain | Hospital Universitary de Bellvitge | Barcelona | |
| Spain | Hospital Clínico Universitario San Carlos | Madrid | |
| Spain | Hospital Universitario 12 de Octubre | Madrid | |
| Spain | Hospital Universitario La Paz | Madrid | |
| Sweden | Karolinska Institutet | Stockholm | |
| Switzerland | University Hospital Basel | Basel | |
| Switzerland | Geneva University Hospital | Genève | |
| United Kingdom | NHS Greater Glasgow | Glasgow | |
| United Kingdom | Barts & The London NHS Trust | London | |
| United Kingdom | Chelsea & Westminster Hospital | London | |
| United Kingdom | Mortimer Market Centre | London | |
| United Kingdom | The Royal Free Hampstead NHS Trust | London | |
| United Kingdom | The Hathersage Integrated Contraception, Sexual Health and HIV Service | Manchester | |
| 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 | The University of Alabama at Birmingham (UAB) | Birmingham | Alabama |
| United States | Brigham and Women's | Boston | Massachusetts |
| United States | Community Research Initiative | Boston | Massachusetts |
| 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 | Carolinas Medical Center--Myers Park Infectious Disease Clinic | Charlotte | North Carolina |
| United States | North Texas Infectious Diseases Consultants | 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 | 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 | AIDS Healthcare Foundation | Miami | Florida |
| United States | AIDS Healthcare Foundation | Miami Beach | Florida |
| United States | Medical College of Wisconsin | Milwaukee | Wisconsin |
| United States | Hennepin County Medical Center | Minneapolis | Minnesota |
| United States | Jersey Shore Medical Center | Neptune | New Jersey |
| United States | Yale University School of Medicine | New Haven | Connecticut |
| United States | Icahn School of Medicine at Mount Sinai | 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 | Alameda County Medical Center | Oakland | California |
| United States | Orlando Immunology Center | Orlando | Florida |
| United States | Desert Medical Group Inc., dba Desert Oasis Healthcare Medical Group | Palm Springs | California |
| United States | Infectious Diseases Associates of NW Florida, P.A. | Pensacola | Florida |
| United States | University of Pennsylvania | Philadelphia | Pennsylvania |
| United States | Spectrum Medical Group | Phoenix | Arizona |
| 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 | Dupont Circle Physicians Group | Washington | District of Columbia |
| United States | Medical Faculty Associates | 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 |
| Lead Sponsor | Collaborator |
|---|---|
| Gilead Sciences |
United States, Belgium, Canada, France, Germany, Italy, Netherlands, Puerto Rico, Spain, Sweden, Switzerland, United Kingdom,
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, 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.
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.
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 [Poster427]. 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, 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/T
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 Kingdo
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 disopro — View 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.
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
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
* Note: There are 12 references in all — Click here to view all references
| 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 US FDA-defined 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 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 | 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 |
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