Clinical trial NCT01705574: Safety and Efficacy of E/C/F/TDF Versus RTV-Boosted ATV Plus FTC/TDF in HIV-1 Infected, Antiretroviral Treatment-Naive Women
Official title: A Randomized, Double-blind Phase 3B Study to Evaluate the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Versus Ritonavir-Boosted Atazanavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naïve Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acquired Immunodeficiency Syndrome
HIV Infections
Keywords: HIV-1
HIV
Treatment-Naive
Women
WAVES
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2012-10-12
Enrollment: 583
Sex: FEMALE
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 efficacy of a regimen containing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) versus ritonavir (RTV)-boosted atazanavir (ATV/r) plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in HIV-1 infected, antiretroviral treatment-naive adult women.


Eligibility criteria: Key Inclusion Criteria:

* Female (at birth), age ≥ 18 years
* Ability to understand and sign a written informed consent form
* Plasma HIV-1 RNA levels ≥ 500 copies/mL
* No prior use of any approved or investigational antiretroviral drug for any length of time
* Screening genotype report must show sensitivity to emtricitabine (FTC), tenofovir disoproxil fumarate (TDF) and atazanavir (ATV) boosted with ritonavir (RTV)
* Normal ECG
* Adequate renal function: Estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula
* Hepatic transaminases ≤ 5 x upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 mg/dL
* Adequate hematologic function
* Serum amylase ≤ 5 x ULN
* Women of childbearing potential must agree to utilize protocol recommended contraception methods or be non-heterosexually active, or practice sexual abstinence from screening throughout the duration of the study period and for 30 days following the last dose of study drug
* Women 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.

Key Exclusion Criteria:

* A new AIDS defining condition diagnosed within the 30 days
* Females receiving drug treatment for Hepatitis C, or females who are anticipated to receive treatment for Hepatitis C during the course of the study
* Females experiencing decompensated cirrhosis
* Females who are breastfeeding
* Positive serum pregnancy test (female of childbearing potential)
* Have an implanted defibrillator or pacemaker
* Have an ECG pulse rate interval ≥ 220 msec
* Current alcohol or substance use which may potentially interfere with the female's study compliance
* History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
* Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
* Participation in any other clinical trial without prior approval
* Any other clinical condition or prior therapy that would make the female unsuitable for the study or unable to comply with the dosing requirements
* Females receiving ongoing therapy with any disallowed medications, including drugs not to be used with elvitegravir, cobicistat, FTC, TDF, ATV, RTV; or females with any known allergies to the excipients of Stribild® tablets, Truvada® tablets, atazanavir capsules or ritonavir tablets

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

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 of the Double-Blind Phase as Determined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 48
Secondary outcomes:
measure: Change From Baseline in CD4+ Cell Count at Week 48 of the Double-Blind Phase
timeFrame: Baseline; Week 48
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 for the STB Group as Determined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 96
measure: Percentage of Participants Receiving STB or ATV+RTV+TVD With HIV-1 RNA < 50 Copies/mL at Week 48 of the Open-Label Extension Phase
timeFrame: Open-Label Extension Week 48
measure: Change in CD4+ Cell Count at Week 48 of the Open-Label Extension Phase
timeFrame: Baseline; Open-Label Extension Week 48
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California AIDS Clinical Trials Group
state: California
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: Washington
country: United States
facility: Whitman-Walker Health
state: District of Columbia
city: Washington
country: United States
facility: George Washington University Medical Faculty Associates
state: District of Columbia
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Orlando
country: United States
facility: IDOCF/ValuhealthMD
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Hospital Comprehensive Research Institute
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A.
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Emory HIV/AIDS Clinical Trials Unit
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta
state: Georgia
city: Macon
country: United States
facility: Mercer University Mercer Medicine
state: Georgia
city: Savannah
country: United States
facility: Chatham County Health Daprtment
state: Georgia
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: LSUHSC HIV Out-Patient Clinic Research
state: Louisiana
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Springfield
country: United States
facility: The Research Institute
state: Massachusetts
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: Newark
country: United States
facility: New Jersey Medical School
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Flushing
country: United States
facility: New York Hospital Queens
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina AIDS Clinical Trials Unit
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University The Brody School of Medicine Div. of Infectious Diseases
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Columbus
country: United States
facility: Wexner Medical Center at the Ohio State University
state: Ohio
city: Toledo
country: United States
facility: The University of Toledo Medical Center
state: Ohio
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia FIGHT
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital- Internal General Medicine
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
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: Bellaire
country: United States
facility: UT - Physicians
state: Texas
city: Dallas
country: United States
facility: AIDS Arms, Inc./Trinity Health & Wellness Center
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants, PA
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, PA
state: Texas
city: Antwerp
country: Belgium
facility: Institute of Tropical Medicine
city: Brussels
country: Belgium
facility: Saint-Pierre University Hospital
city: Brussels
country: Belgium
facility: Hôpitaux IRIS SUD
city: Santo Domingo
country: Dominican Republic
facility: Instituto Dominicano de Estudio Virologicos - IDEV
city: Santo Domingo
country: Dominican Republic
facility: Salvador B Gautier Hospital, Infectious Diseases Department
city: Paris
country: France
facility: Hôpital Bichat Claude Bernard
city: Paris
country: France
facility: Hopital Tenon
city: Paris
country: France
facility: Maladies Infectieuses Dpt
city: Strasbourg
country: France
facility: Hopitaux Universitaires Strasbourg
city: Milan
country: Italy
facility: Department of Health Sciences - University of Milan - San Paolo Hospital
city: Milan
country: Italy
facility: Luigi Sacco Hospital, Milan
city: Modena
country: Italy
facility: Clinica Malattie Infettive, Azienda Ospedaliero Universitaria
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Dr Juan I Menchaca
state: Jalisco
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara
city: Mexico City
country: Mexico
facility: Intituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
city: Amadora
country: Portugal
facility: Hospital Fernando Fonseca
city: Lisboa
country: Portugal
facility: Hospital Dos Capuchos, Centro Hospitalar De Lisboa Central
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria - Serviço de Doenças Infecciosas
city: Porto
country: Portugal
facility: centro Hospitalar S. João
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto - Hospital Joaquim Urbano
city: Santarem
country: Portugal
facility: Hospital de Santarém
city: San Juan
country: Puerto Rico
facility: Maternal Infants Studies Center (CEMI)
city: Barnaul
country: Russian Federation
facility: Republic of Altay Center for Prevention and Control of AIDS and Infectious Diseases
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Center for Prevention and control of AIDS and Infectious Diseases
city: Irkutsk
country: Russian Federation
facility: GUZ "Irkutsk Regional Center for Prevention and Control of AIDS and Infectious Diseases
city: Khabarovsk
country: Russian Federation
facility: Khabarovsk Territorial Center for Prevention and Control of AIDS and Infectious Diseases
city: Koltsovo
country: Russian Federation
facility: "Infectious Diseases Center", LLC
city: Krasnodar
country: Russian Federation
facility: State Budget Healthcare Institution "Clinical Centre for AIDS and Infectious Diseases Fight and Prevention" of Krasnodar regio Department for Healthcare
city: Krasnoyarsk
country: Russian Federation
facility: GUZ "Krasnoyarsk Territorial Center for Prevention and Control of AIDS and Infectious Diseases"
city: Lipetsk
country: Russian Federation
facility: GUZ "Lipetsk Regional Center for Prevention and Control of AIDS and Infectious Diseases"
city: Moscow
country: Russian Federation
facility: Infectious Hospital 2
city: Moscow
country: Russian Federation
facility: State Healthcare Institution Infectious Clinical Hospital #2 of Moscow City Healthcare Department
city: Moscow
country: Russian Federation
facility: GKUZ MO "Center for Prevention and Treatment of AIDS and Infectious Diseases" (Moscow Regional AIDS Center)
city: Nizhniy Novgorod
country: Russian Federation
facility: State Budget Health Institution of Nizhniy Novgorod "Nizhniy Novgorod Regional Center of prophylaxis and treatment of AIDS and Infectious Diseases
city: Orel
country: Russian Federation
facility: Budgetary Medical Facility of the Orel Region "Orel Regional Center for Prevention and Control of AIDS and Infectious Diseases"
city: Perm
country: Russian Federation
facility: Perm Regional Center for Prevention and Control of AIDS and Infectious Diseases
city: Saint-Petersburg
country: Russian Federation
facility: St.Petersburg Center for Prevention and Control of AIDS and Infectious Diseases, In-patient Department
city: Saint-Petersburg
country: Russian Federation
facility: St.Petersburg GUZ "Center for Prevention and Control of AIDS and Infectious Diseases", Out-patient Department
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg GUZ "Clinical Infectious Hospital named after S.P.Botkin"
city: Saint-Petersburg
country: Russian Federation
facility: Federal State Budgetary Institution "Republic Clinical Infectious Hospital"
city: Saratov
country: Russian Federation
facility: Saratov Regional Centre for Treatment and Prevention of AIDS and Infectious Diseases
city: Volgograd
country: Russian Federation
facility: Volgograd Regional Center for Prevention and Control of AIDS and Infectious Diseases
city: Voronezh
country: Russian Federation
facility: GUZ "Voronezh Regional Center for Prevention and Control of AIDS and Infectious Diseases"
city: Bangkok
country: Thailand
facility: The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)
city: Bangkok
country: Thailand
facility: Faculty of Medicine Ramathibodi Hospital, Mahidol University
city: Bangkok
country: Thailand
facility: Department of Preventive and Social Medicine, Faculty of Medicine, Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Chiang Mai University
city: Nonthaburi
country: Thailand
facility: Bamrasnaradura lnfectious Disease Institute
city: Kampala
country: Uganda
facility: Joint Clinical Research Centre
city: London
country: United Kingdom
facility: Barts Healthe NHS Trust
city: London
country: United Kingdom
facility: Homerton University Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: Queen Elizabeth Hospital, South London Healthcare NHS Trust
city: London
country: United Kingdom
facility: Kings College London
city: London
country: United Kingdom
facility: St George's Healthcare NHS Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: Mortimer Market Centre and Central and North West London NHS Foundation Trust
city: Reading
country: United Kingdom
facility: Royal Berkshire NHS Foundation Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Squires K, Kityo C, Hodder S, Johnson M, Voronin E, Hagins D, Avihingsanon A, Koenig E, Jiang S, White K, Cheng A, Szwarcberg J, Cao H. Integrase inhibitor versus protease inhibitor based regimen for HIV-1 infected women (WAVES): a randomised, controlled, double-blind, phase 3 study. Lancet HIV. 2016 Sep;3(9):e410-e420. doi: 10.1016/S2352-3018(16)30016-9. Epub 2016 May 27.
citation: Hodder S, Squires K, Gathe J, Kityo C, Supparatpinyo K, Moshkovich G, et al. Elvitegravir (EVG)/cobicistat (COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) is superior to ritonavir (RTV)-boosted atazanavir (ATV) plus FTC/TDF in treatment-naive women with HIV-1 infection (WAVES study). Presented at Interscience Conference on Antimicrobial Agents and Chemotherapy and International Congress of Chemotherapy and Infection (ICAAC/ICC) 2015; September 17-21; San Diego, CA.
citation: Squires K, Kityo C, Hodder S, Hagins D, Avihingsanon A, Plotnikova Y, et al. Elvitegravir (EVG)/cobicistat (COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) is superior to ritonavir (RTV)-boosted atazanavir (ATV) plus FTC/TDF in treatment-naive women with HIV-1 infection (WAVES study). Poster no. MOLBPE08. Presented at 8th International Antiviral Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention, 2015; 19-22 July, Vancouver, BC, Canada.
citation: Hodder S, Kityo C, Koenig E, Mussini C, Post F, Romanova S, et al. Genotypic analysis of the global clinical trial of treatment-naive women. Abstract 16. Presented at 5th International Workshop on HIV & Women, 2015; 21-22 February, Seattle, WA.
citation: Squires K, Hodder S, Kityo C, Clumeck N, Johnson M, Plotnikova Y, et al. Enrollment in the Women's Antiretroviral Efficacy and Safety study (WAVES), a Phase 3 global study assessing antiretroviral regimen in treatment-naive women. Abstract 54. Presented at 5th International Workshop on HIV & Women, 2015; 21-22 February, Seattle, WA.