HIV Infections Clinical Trial
Official title:
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Positive, Antiretroviral Treatment-Naïve Adults
Verified date | October 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 efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) versus elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) in HIV-1 positive, antiretroviral treatment-naive adults.
Status | Completed |
Enrollment | 872 |
Est. completion date | October 3, 2018 |
Est. primary completion date | September 19, 2014 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Key Inclusion Criteria: - Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures - Plasma HIV-1 RNA levels = 1,000 copies/mL at screening - No prior use of any approved or investigational antiretroviral drug for any length of time, except the use for pre-exposure prophylaxis (PREP), or post-exposure prophylaxis (PEP) up to 6 months prior to screening - Screening genotype report must show sensitivity to elvitegravir, emtricitabine, tenofovir DF - Normal electrocardiogram (ECG) - Estimated glomerular filtration rate (eGFR) = 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 - Males and females of childbearing potential 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 - Females who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing - Females who have stopped menstruating for = 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range - Age = 18 years Key Exclusion Criteria: - A new AIDS-defining condition diagnosed within the 30 days prior to screening - Hepatitis B surface antigen (HBsAg) positive - Hepatitis C antibody positive - Individuals experiencing decompensated cirrhosis - Females who are breastfeeding - Positive serum pregnancy test - Have an implanted defibrillator or pacemaker - Current alcohol or substance use judged by the Investigator to potentially interfere with study compliance - History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma - Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline - 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 - Receiving ongoing therapy with drugs not to be used with elvitegravir, cobicistat, emtricitabine, tenofovir DF, and TAF or participants with any known allergies to the excipients of E/C/F/TDF or E/C/F/TAF Note: Other protocol defined Inclusion/Exclusion criteria may apply. |
Country | Name | City | State |
---|---|---|---|
Canada | Clinique Medicale L'actuel | Montreal | |
Canada | Research Institute of McGill University Health Care | Montreal | Quebec |
Canada | Maple Leaf Research | Toronto | |
Canada | University Health Network/Toronto General Hospital | Toronto | |
Canada | Spectrum Health Care | Vancouver | |
Dominican Republic | Instituto Dominicano de Estudios Virologicos--IDEV | Santo Domingo | |
France | Hopital de la Croix Rousse | Lyon | |
France | University Hospital of Montpellier (CHU-Gui de Chauliac) | Montpellier | |
France | Archet 1 CHU de Nice, Department of Infectiology | Nice | |
France | Hôpital Bichat Claude Bernard | Paris | |
France | Hopital Pitie Salpetriere | Paris | |
France | Hopital Saint Antoine | Paris | |
France | Hopital Tenon | Paris | |
France | Saint Louis Hospital of Infectious Diseases | Paris | |
France | CH Tourcoing | Tourcoing | |
Italy | Universitaria di Bologna-Policlicnico S' Orsola Malpighi | Bologna | |
Italy | IRCCS Ospedale San Raffaele | Milan | |
Mexico | Hospital Civil de Guadalajara | Guadalajara | |
Mexico | Insituto Nacional De Enfermedades Respiratorias "Ismael Cosio Villegas" | Mexico City | |
Netherlands | Onze Lieve Vrouwe Gasthuis | Amsterdam | |
Portugal | Serviço de Doenças Infecciosas, HUC-CHUC, EPE | Coimbra | |
Portugal | Hospital Santo Antonio dos Capuchos | Lisboa | |
Portugal | Hospital de Santa Maria - CHLN, EPE | Lisbon | |
Portugal | Centro Hospitalar do Porto - Hospital Joaquim Urbano | Porto | |
Puerto Rico | Hope Clinical Research | San Juan | |
Puerto Rico | University of Puerto Rico ACTU | San Juan | |
Sweden | Karolinska University Hospital, Huddinge | Stockholm | |
Sweden | Venhalsan / Sodersjukhuset | Stockholm | |
United Kingdom | Heart Of England NHS Foundation Trust | Birmingham | |
United Kingdom | Whittall Street Clinic | Birmingham | |
United Kingdom | Brighton and Sussex University Hospitals NHS Trust | Brighton | |
United Kingdom | Brownlee Centre, Gartnavel General Hospital | Glasgow | |
United Kingdom | Barts Health NHS Trust | London | |
United Kingdom | Chelsea and Westminster | London | |
United Kingdom | Kings College Hospital | London | |
United Kingdom | Mortimer Market Centre | London | |
United Kingdom | Royal Free London NHS Foundation Trust | London | |
United Kingdom | North Manchester General Hospital | Manchester | |
United States | Albany Medical College | Albany | New York |
United States | Upstate ID Assoc | Albany | New York |
United States | Clinical Alliance for Research & Education - Infectious Diseases (CARE-ID) | Annandale | Virginia |
United States | AIDS Research Consortium of Atlanta | Atlanta | Georgia |
United States | Atlanta ID Group, PC | Atlanta | Georgia |
United States | Emory University | Atlanta | Georgia |
United States | Georgia Regents University | Augusta | Georgia |
United States | University of Colorado | Aurora | Colorado |
United States | Central Texas Clinical Research | Austin | Texas |
United States | St. Hope Foundation, Inc. | Bellaire | Texas |
United States | Be Well Medical Center | Berkley | Michigan |
United States | University of Alabama at Birmingham | Birmingham | Alabama |
United States | Community Research Initiative of New England | Boston | Massachusetts |
United States | Jacobi Medical Center | Bronx | New York |
United States | Montefiore Medical Center | Bronx | New York |
United States | University of North Carolina AIDS Clinical Trials Unit | Chapel Hill | North Carolina |
United States | Carolinas Medical Center Myer's Park Clinic | Charlotte | North Carolina |
United States | Rush University Medical Center, Section of Infectious Diseases | Chicago | Illinois |
United States | The Ruth M. Rothstein CORE Center | Chicago | Illinois |
United States | North Texas Infectious Diseases Consultants | Dallas | Texas |
United States | Southwest Infectious Disease Clinical Research, Inc. | Dallas | Texas |
United States | Trinity Health & Wellness Center / AIDS Arms, Inc. | Dallas | Texas |
United States | Infectious Disease Specialist of Atlanta | Decatur | Georgia |
United States | APEX Research LLC | Denver | Colorado |
United States | Henry Ford Health System | Detroit | Michigan |
United States | Duke University Medical Center | Durham | North Carolina |
United States | Gary J. Richmond,M.D.,P.A. | 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 | East Carolina University The Brody School of Medicine | Greenville | North Carolina |
United States | Greenwich Hospital | Greenwich | Connecticut |
United States | ID Care | Hillsborough | New Jersey |
United States | University of Hawaii - Hawaii Center for AIDS | Honolulu | Hawaii |
United States | Gordon E. Crofoot, MD, PA | Houston | Texas |
United States | Research Access Network | Houston | Texas |
United States | Therapeutic Concepts, PA | Houston | Texas |
United States | Rosedale Infectious Disseases | Huntersville | North Carolina |
United States | DCOL Center for Clinical Research | Longview | Texas |
United States | Anthony Mills MD Inc | Los Angeles | California |
United States | Kaiser Permanente - Los Angeles Medical Center | Los Angeles | California |
United States | Peter J. Ruane, Inc. | Los Angeles | California |
United States | University of Southern California AIDS Clinical Trials Group | Los Angeles | California |
United States | Mercer University | Macon | Georgia |
United States | North Shore University Hospital - Division of Infectious Diseases | Manhasset | New York |
United States | AIDS Healthcare Foundation | Miami | Florida |
United States | AIDS Healthcare Foundation | Miami Beach | Florida |
United States | Hennepin County Medical Center | Minneapolis | Minnesota |
United States | Yale University | New Haven | Connecticut |
United States | Chelsea Village Medical | New York | New York |
United States | Columbia University Medical Center | New York | New York |
United States | Weill Cornell Medical College | New York | New York |
United States | Alameda County Medical Center | Oakland | California |
United States | Idocf/Valuhealthmd | Orlando | Florida |
United States | Orlando Immunology Center | Orlando | Florida |
United States | Stanford University | Palo Alto | California |
United States | University of Pennsylvania | Philadelphia | Pennsylvania |
United States | Spectrum Medical Group | Phoenix | Arizona |
United States | The Miriam Hospital | Providence | Rhode Island |
United States | Kaiser Permanente Medical Group | Sacramento | California |
United States | University of California, Davis Medical Center | Sacramento | California |
United States | Central West Clinical Research | Saint Louis | Missouri |
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 | San Francisco | California |
United States | Kaiser Permanente | San Leandro | California |
United States | Southwest CARE Center | Santa Fe | New Mexico |
United States | Infectious Diseases Associates of NW FL | Sarasota | Florida |
United States | Peter Shalit, MD | Seattle | Washington |
United States | Infectious Disease Research Institute Inc. | Tampa | Florida |
United States | St. Joseph's Comprehensive Research Institute | Tampa | Florida |
United States | University of South Florida | Tampa | Florida |
United States | Los Angeles Biomedical Research Institute at Harbor - UCLA Medical Center | Torrance | California |
United States | Capital Medical Associates, PC | 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 Health | Washington | District of Columbia |
United States | Triple O Research Institute PA | West Palm Beach | Florida |
United States | The Research Institute | West Springfield | Massachusetts |
United States | Wake Forest University Health Sciences | Winston-Salem | North Carolina |
Lead Sponsor | Collaborator |
---|---|
Gilead Sciences |
United States, Canada, Dominican Republic, France, Italy, Mexico, Netherlands, Portugal, Puerto Rico, Sweden, United Kingdom,
Arribas JR, Thompson M, Sax PE, Haas B, McDonald C, Wohl DA, DeJesus E, Clarke AE, Guo S, Wang H, Callebaut C, Plummer A, Cheng A, Das M, McCallister S. Brief Report: Randomized, Double-Blind Comparison of Tenofovir Alafenamide (TAF) vs Tenofovir Disoprox — View Citation
Custodio JM, Garner W, Callebaut C, Fordyce M, Plummer A, Zhong L, et al. The Pharmacokinetics of Tenofovir and Tenofovir Diphosphate Following Administration of Tenofovir Alafenamide vs Tenofovir Disoproxil Fumarate [Oral Abstract #6]. The 16th Internati
Funderburg NT, McComsey GA, Kulkarni M, Bannerman T, Mantini J, Thornton B, Liu HC, Zhang Y, Song Q, Fang L, Dinoso J, Cheng A, McCallister S, Fordyce MW, Das M. Equivalent Decline in Inflammation Markers with Tenofovir Disoproxil Fumarate vs. Tenofovir A — View Citation
Margot N, Cox S, Das M, McCallister S, Miller MD, Callebaut C. Infrequent development of drug resistance in HIV-1-infected treatment-naive subjects after 96 weeks of treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or elvitegravi — View Citation
Margot N, Cox S, Das M, McCallister S, Miller MD, Callebaut C. Rare emergence of drug resistance in HIV-1 treatment-naïve patients receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide for 144 weeks. J Clin Virol. 2018 Jun;103:37-42. doi: — View Citation
Margot NA, Kitrinos KM, Fordyce M, McCallister S, Miller MD, Callebaut C. Rare emergence of drug resistance in HIV-1 treatment-naïve patients after 48 weeks of treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. HIV Clin Trials. 20 — View Citation
Sax PE, Wohl D, Yin MT, Post F, DeJesus E, Saag M, Pozniak A, Thompson M, Podzamczer D, Molina JM, Oka S, Koenig E, Trottier B, Andrade-Villanueva J, Crofoot G, Custodio JM, Plummer A, Zhong L, Cao H, Martin H, Callebaut C, Cheng AK, Fordyce MW, McCallist — View Citation
Wohl D, Oka S, Clumeck N, Clarke A, Brinson C, Stephens J, Tashima K, Arribas JR, Rashbaum B, Cheret A, Brunetta J, Mussini C, Tebas P, Sax PE, Cheng A, Zhong L, Callebaut C, Das M, Fordyce M; GS-US-2,92-01040111 and Study Team. Brief Report: A Randomized — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48 | 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 96 | The percentage of participants achieving 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 < 20 Copies/mL at Weeks 48 and 96 | The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Weeks 48 and 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. | Weeks 48 and 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 Serum Creatinine at Week 48 | Baseline; Week 48 | ||
Secondary | Change From Baseline in Serum Creatinine at Week 96 | Baseline; Week 96 | ||
Secondary | Percentage of Participants With Treatment-emergent Proteinuria Through Week 48 | Grades 1 (mild), 2 (moderate), and 3 (severe) were the highest treatment-emergent postbaseline grades for urine protein using the dipstick method. The worst postbaseline value is presented for each participant. | Baseline to Week 48 | |
Secondary | Percentage of Participants With Treatment-emergent Proteinuria Through Week 96 | Grades 1 (mild), 2 (moderate), and 3 (severe) were the highest treatment-emergent postbaseline grades for urine protein using the dipstick method. The worst postbaseline value is presented for each participant. | Baseline to Week 96 | |
Secondary | Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48 | Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury. | Baseline; Week 48 | |
Secondary | Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96 | Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury. | Baseline; Week 96 | |
Secondary | Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 48 | Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury. | Baseline; Week 48 | |
Secondary | Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 96 | Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury. | Baseline; Week 96 |
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