Safety and Efficacy of E/C/F/TDF Versus RTV-Boosted ATV Plus FTC/TDF in HIV-1 Infected, Antiretroviral Treatment-Naive Women (WAVES)

September 5, 2019 updated by: Gilead Sciences

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

583

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Antwerp, Belgium, 2000
        • Institute of Tropical Medicine
      • Brussels, Belgium, 1000
        • Saint-Pierre University Hospital
      • Brussels, Belgium, 1050
        • Hôpitaux IRIS Sud
  • Dominican Republic
      • Santo Domingo, Dominican Republic, 10514
        • Instituto Dominicano de Estudio Virologicos - IDEV
      • Santo Domingo, Dominican Republic, 10514
        • Salvador B Gautier Hospital, Infectious Diseases Department
  • France
      • Paris, France, 75020
        • Hopital Tenon
      • Paris, France, 75018
        • Hopital Bichat Claude Bernard
      • Paris, France, 75651
        • Maladies Infectieuses Dpt
      • Strasbourg, France, 67091
        • Hôpitaux Universitaires Strasbourg
  • Italy
      • Milan, Italy, 20142
        • Department of Health Sciences - University of Milan - San Paolo Hospital
      • Milan, Italy, 20157
        • Luigi Sacco Hospital, Milan
      • Modena, Italy, 41124
        • Clinica Malattie Infettive, Azienda Ospedaliero Universitaria
  • Mexico
      • Guadalajara, Mexico, 44280
        • Hospital Civil de Guadalajara
      • Mexico City, Mexico, 14000
        • Intituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44340
        • Hospital Civil de Guadalajara Dr Juan I Menchaca
  • Portugal
      • Amadora, Portugal, 2720-276
        • Hospital Fernando Fonseca
      • Lisboa, Portugal, 1200-110
        • Hospital Dos Capuchos, Centro Hospitalar De Lisboa Central
      • Lisboa, Portugal, 1649-035
        • Hospital de Santa Maria - Serviço de Doenças Infecciosas
      • Porto, Portugal, 4200-319
        • Centro Hospitalar S. Joao
      • Porto, Portugal, 4369-004
        • Centro Hospitalar do Porto - Hospital Joaquim Urbano
      • Santarem, Portugal, 2005-177
        • Hospital de Santarem
  • Puerto Rico
      • San Juan, Puerto Rico, 00936
        • Maternal Infants Studies Center (CEMI)
  • Russian Federation
      • Barnaul, Russian Federation, 656010
        • Republic of Altay Center for Prevention and Control of AIDS and Infectious Diseases
      • Ekaterinburg, Russian Federation, 620102
        • Sverdlovsk Regional Center for Prevention and control of AIDS and Infectious Diseases
      • Irkutsk, Russian Federation, 664043
        • GUZ "Irkutsk Regional Center for Prevention and Control of AIDS and Infectious Diseases
      • Khabarovsk, Russian Federation, 680031
        • Khabarovsk Territorial Center for Prevention and Control of AIDS and Infectious Diseases
      • Koltsovo, Russian Federation, 630559
        • "Infectious Diseases Center", LLC
      • Krasnodar, Russian Federation, 350015
        • State Budget Healthcare Institution "Clinical Centre for AIDS and Infectious Diseases Fight and Prevention" of Krasnodar regio Department for Healthcare
      • Krasnoyarsk, Russian Federation, 660049
        • GUZ "Krasnoyarsk Territorial Center for Prevention and Control of AIDS and Infectious Diseases"
      • Lipetsk, Russian Federation, 398043
        • GUZ "Lipetsk Regional Center for Prevention and Control of AIDS and Infectious Diseases"
      • Moscow, Russian Federation, 105275
        • Infectious Hospital 2
      • Moscow, Russian Federation, 105275
        • State Healthcare Institution Infectious Clinical Hospital #2 of Moscow City Healthcare Department
      • Moscow, Russian Federation, 129110
        • GKUZ MO "Center for Prevention and Treatment of AIDS and Infectious Diseases" (Moscow Regional AIDS Center)
      • Nizhniy Novgorod, Russian Federation, 603950
        • State Budget Health Institution of Nizhniy Novgorod "Nizhniy Novgorod Regional Center of prophylaxis and treatment of AIDS and Infectious Diseases
      • Orel, Russian Federation, 302040
        • Budgetary Medical Facility of the Orel Region "Orel Regional Center for Prevention and Control of AIDS and Infectious Diseases"
      • Perm, Russian Federation, 614000
        • Perm Regional Center for Prevention and Control of AIDS and Infectious Diseases
      • Saint-Petersburg, Russian Federation, 190020
        • St.Petersburg Center for Prevention and Control of AIDS and Infectious Diseases, In-patient Department
      • Saint-Petersburg, Russian Federation, 190103
        • St.Petersburg GUZ "Center for Prevention and Control of AIDS and Infectious Diseases", Out-patient Department
      • Saint-Petersburg, Russian Federation, 191167
        • Saint-Petersburg GUZ "Clinical Infectious Hospital named after S.P.Botkin"
      • Saint-Petersburg, Russian Federation, 196645
        • Federal State Budgetary Institution "Republic Clinical Infectious Hospital"
      • Saratov, Russian Federation, 410009
        • Saratov Regional Centre for Treatment and Prevention of AIDS and Infectious Diseases
      • Volgograd, Russian Federation, 400040
        • Volgograd Regional Center for Prevention and Control of AIDS and Infectious Diseases
      • Voronezh, Russian Federation, 394065
        • GUZ "Voronezh Regional Center for Prevention and Control of AIDS and Infectious Diseases"
  • Thailand
      • Bangkok, Thailand, 10330
        • The HIV Netherlands Australia Thailand Research collaboration (HIV-NAT)
      • Bangkok, Thailand, 10400
        • Faculty of Medicine Ramathibodi Hospital, Mahidol University
      • Bangkok, Thailand, 10700
        • Department of Preventive and Social Medicine, Faculty of Medicine, Siriraj Hospital
      • Chiang Mai, Thailand, 50200
        • Chiang Mai University
      • Nonthaburi, Thailand, 11000
        • Bamrasnaradura lnfectious Disease Institute
  • Uganda
      • Kampala, Uganda
        • Joint Clinical Research Centre
  • United Kingdom
      • London, United Kingdom, NW32QG
        • Royal Free London NHS Foundation Trust
      • London, United Kingdom, SW17 0QT
        • St George's Healthcare NHS Trust
      • London, United Kingdom, E11BB
        • Barts Healthe NHS Trust
      • London, United Kingdom, E96SR
        • Homerton University Hospital NHS Foundation Trust
      • London, United Kingdom, SE18 4QH
        • Queen Elizabeth Hospital, South London Healthcare NHS Trust
      • London, United Kingdom, SE59RJ
        • Kings College London
      • London, United Kingdom, W21NY
        • Imperial College Healthcare NHS Trust
      • London, United Kingdom, WC1E 6JB
        • Mortimer Market Centre and Central and North West London NHS Foundation Trust
      • Reading, United Kingdom, RG1 5LE
        • Royal Berkshire NHS foundation trust
  • United States
    • California
      • Los Angeles, California, United States, 90033
        • University of Southern California AIDS Clinical Trials Group
      • Sacramento, California, United States, 95817
        • University of California, Davis Medical Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20037
        • George Washington University Medical Faculty Associates
      • Washington, District of Columbia, United States, 20009
        • Whitman-Walker Health
    • Florida
      • Fort Pierce, Florida, United States, 34982
        • Midway Immunology and Research Center
      • Miami, Florida, United States, 33136
        • University of Miami
      • Orlando, Florida, United States, 32803
        • Orlando Immunology Center
      • Orlando, Florida, United States, 32806
        • Idocf/Valuhealthmd
      • Tampa, Florida, United States, 33614
        • St. Joseph's Hospital Comprehensive Research Institute
      • West Palm Beach, Florida, United States, 33401
        • Triple O Research Institute, P.A.
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • AIDS Research Consortium of Atlanta
      • Atlanta, Georgia, United States, 30308
        • Emory HIV/AIDS Clinical Trials Unit
      • Decatur, Georgia, United States, 30033
        • Infectious Disease Specialists of Atlanta
      • Macon, Georgia, United States, 31201
        • Mercer University Mercer Medicine
      • Savannah, Georgia, United States, 31401
        • Chatham County Health Daprtment
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • University of Louisville
    • Louisiana
      • New Orleans, Louisiana, United States, 70119
        • LSUHSC HIV Out-Patient Clinic Research
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Springfield, Massachusetts, United States, 01105
        • The Research Institute
    • New Jersey
      • Newark, New Jersey, United States, 07102
        • Saint Michael's Medical Center
      • Newark, New Jersey, United States, 07103
        • New Jersey Medical School
    • New York
      • Bronx, New York, United States, 10040
        • Montefiore Medical Center
      • Flushing, New York, United States, 01135
        • New York Hospital Queens
      • Rochester, New York, United States, 14642
        • University of Rochester
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina AIDS Clinical Trials Unit
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Greenville, North Carolina, United States, 27834
        • East Carolina University The Brody School of Medicine Div. of Infectious Diseases
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Wexner Medical Center at the Ohio State University
      • Toledo, Ohio, United States, 43614
        • The University of Toledo Medical Center
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18102
        • Lehigh Valley Health Network
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
      • Philadelphia, Pennsylvania, United States, 19107
        • Philadelphia FIGHT
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University Hospital- Internal General Medicine
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • The Miriam Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Texas
      • Austin, Texas, United States, 78705
        • Central Texas Clinical Research
      • Bellaire, Texas, United States, 77401
        • UT - Physicians
      • Dallas, Texas, United States, 75208
        • AIDS Arms, Inc./Trinity Health & Wellness Center
      • Dallas, Texas, United States, 75208
        • North Texas Infectious Diseases Consultants, PA
      • Houston, Texas, United States, 77004
        • Therapeutic Concepts, PA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: E/C/F/TDF
E/C/F/TDF + ATV placebo + RTV placebo + FTC/TDF placebo
Drug: E/C/F/TDF
150/150/200/300 mg FDC tablet administered orally with food once daily
Other Names:
  • Stribild®
Drug: ATV Placebo
Tablet administered orally with food once daily
Drug: RTV Placebo
Capsule administered orally with food once daily
Drug: FTC/TDF Placebo
Tablet administered orally with food once daily
ACTIVE_COMPARATOR: ATV + RTV+ FTC/TDF
ATV + RTV + FTC/TDF + E/C/F/TDF placebo
Drug: ATV
300 mg capsule administered orally with food once daily
Other Names:
  • Reyataz®
Drug: RTV
100 mg tablet administered orally with food once daily
Other Names:
  • Norvir®
Drug: FTC/TDF
200/300 mg tablet administered orally with food once daily
Other Names:
  • Truvada®
Drug: E/C/F/TDF Placebo
Tablet administered orally with food once daily
EXPERIMENTAL: Open-Label Extension Phase
After 48 weeks of blinded treatment, participants will continue to take blinded study drug for 12 weeks and return for an unblinding visit at Week 60. Participants who are virologically suppressed at Week 48 during the double-blinded treatment phase will have the option to enter the open-label extension phase. Participants randomized to the E/C/F/TDF arm will continue to receive open-label E/C/F/TDF and participants randomized to the ATV+ RTV + FTC/TDF arm will be re-randomized to receive either open-label elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or open-label ATV + RTV+ FTC/TDF.
Drug: E/C/F/TDF
150/150/200/300 mg FDC tablet administered orally with food once daily
Other Names:
  • Stribild®
Drug: ATV
300 mg capsule administered orally with food once daily
Other Names:
  • Reyataz®
Drug: RTV
100 mg tablet administered orally with food once daily
Other Names:
  • Norvir®
Drug: FTC/TDF
200/300 mg tablet administered orally with food once daily
Other Names:
  • Truvada®
Drug: E/C/F/TAF
150/150/200/10 mg FDC tablet administered orally with food once daily
Other Names:
  • Genvoya®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: Week 48
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 of the double-blind phase was analyzed using the snapshot algorithm, which defines a participant'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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in CD4+ Cell Count at Week 48 of the Double-Blind Phase
Time Frame: Baseline; Week 48
Baseline; Week 48
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
Time Frame: Week 96
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant'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
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
Time Frame: Open-Label Extension Week 48
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 of the open-label phase was analyzed using the snapshot algorithm, which defines a participant'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.
Open-Label Extension Week 48
Change in CD4+ Cell Count at Week 48 of the Open-Label Extension Phase
Time Frame: Baseline; Open-Label Extension Week 48
Baseline; Open-Label Extension Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 24, 2012

Primary Completion (ACTUAL)

February 9, 2015

Study Completion (ACTUAL)

September 6, 2018

Study Registration Dates

First Submitted

October 10, 2012

First Submitted That Met QC Criteria

October 11, 2012

First Posted (ESTIMATE)

October 12, 2012

Study Record Updates

Last Update Posted (ACTUAL)

September 20, 2019

Last Update Submitted That Met QC Criteria

September 5, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-236-0128
  • 2012-003708-11 (EUDRACT_NUMBER)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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