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

NCT ID: NCT01705574

Last Updated: 2019-09-20

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

583 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-24

Study Completion Date

2018-09-06

Brief Summary

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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.

Detailed Description

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Conditions

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Acquired Immunodeficiency Syndrome HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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E/C/F/TDF

E/C/F/TDF + ATV placebo + RTV placebo + FTC/TDF placebo

Group Type EXPERIMENTAL

E/C/F/TDF

Intervention Type DRUG

150/150/200/300 mg FDC tablet administered orally with food once daily

ATV Placebo

Intervention Type DRUG

Tablet administered orally with food once daily

RTV Placebo

Intervention Type DRUG

Capsule administered orally with food once daily

FTC/TDF Placebo

Intervention Type DRUG

Tablet administered orally with food once daily

ATV + RTV+ FTC/TDF

ATV + RTV + FTC/TDF + E/C/F/TDF placebo

Group Type ACTIVE_COMPARATOR

ATV

Intervention Type DRUG

300 mg capsule administered orally with food once daily

RTV

Intervention Type DRUG

100 mg tablet administered orally with food once daily

FTC/TDF

Intervention Type DRUG

200/300 mg tablet administered orally with food once daily

E/C/F/TDF Placebo

Intervention Type DRUG

Tablet administered orally with food once daily

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.

Group Type EXPERIMENTAL

E/C/F/TDF

Intervention Type DRUG

150/150/200/300 mg FDC tablet administered orally with food once daily

ATV

Intervention Type DRUG

300 mg capsule administered orally with food once daily

RTV

Intervention Type DRUG

100 mg tablet administered orally with food once daily

FTC/TDF

Intervention Type DRUG

200/300 mg tablet administered orally with food once daily

E/C/F/TAF

Intervention Type DRUG

150/150/200/10 mg FDC tablet administered orally with food once daily

Interventions

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E/C/F/TDF

150/150/200/300 mg FDC tablet administered orally with food once daily

Intervention Type DRUG

ATV

300 mg capsule administered orally with food once daily

Intervention Type DRUG

RTV

100 mg tablet administered orally with food once daily

Intervention Type DRUG

FTC/TDF

200/300 mg tablet administered orally with food once daily

Intervention Type DRUG

E/C/F/TDF Placebo

Tablet administered orally with food once daily

Intervention Type DRUG

ATV Placebo

Tablet administered orally with food once daily

Intervention Type DRUG

RTV Placebo

Capsule administered orally with food once daily

Intervention Type DRUG

FTC/TDF Placebo

Tablet administered orally with food once daily

Intervention Type DRUG

E/C/F/TAF

150/150/200/10 mg FDC tablet administered orally with food once daily

Intervention Type DRUG

Other Intervention Names

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Stribild® Reyataz® Norvir® Truvada® Genvoya®

Eligibility Criteria

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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.

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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

University of Southern California AIDS Clinical Trials Group

Los Angeles, California, United States

Site Status

University of California, Davis Medical Center

Sacramento, California, United States

Site Status

Whitman-Walker Health

Washington D.C., District of Columbia, United States

Site Status

George Washington University Medical Faculty Associates

Washington D.C., District of Columbia, United States

Site Status

Midway Immunology and Research Center

Ft. Pierce, Florida, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Orlando Immunology Center

Orlando, Florida, United States

Site Status

IDOCF/ValuhealthMD

Orlando, Florida, United States

Site Status

St. Joseph's Hospital Comprehensive Research Institute

Tampa, Florida, United States

Site Status

Triple O Research Institute, P.A.

West Palm Beach, Florida, United States

Site Status

AIDS Research Consortium of Atlanta

Atlanta, Georgia, United States

Site Status

Emory HIV/AIDS Clinical Trials Unit

Atlanta, Georgia, United States

Site Status

Infectious Disease Specialists of Atlanta

Decatur, Georgia, United States

Site Status

Mercer University Mercer Medicine

Macon, Georgia, United States

Site Status

Chatham County Health Daprtment

Savannah, Georgia, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

LSUHSC HIV Out-Patient Clinic Research

New Orleans, Louisiana, United States

Site Status

The Research Institute

Springfield, Massachusetts, United States

Site Status

Saint Michael's Medical Center

Newark, New Jersey, United States

Site Status

New Jersey Medical School

Newark, New Jersey, United States

Site Status

New York Hospital Queens

Flushing, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

University of North Carolina AIDS Clinical Trials Unit

Chapel Hill, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

East Carolina University The Brody School of Medicine Div. of Infectious Diseases

Greenville, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Wexner Medical Center at the Ohio State University

Columbus, Ohio, United States

Site Status

The University of Toledo Medical Center

Toledo, Ohio, United States

Site Status

Lehigh Valley Health Network

Allentown, Pennsylvania, United States

Site Status

Philadelphia FIGHT

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Temple University Hospital- Internal General Medicine

Philadelphia, Pennsylvania, United States

Site Status

The Miriam Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Central Texas Clinical Research

Austin, Texas, United States

Site Status

UT - Physicians

Bellaire, Texas, United States

Site Status

AIDS Arms, Inc./Trinity Health & Wellness Center

Dallas, Texas, United States

Site Status

North Texas Infectious Diseases Consultants, PA

Dallas, Texas, United States

Site Status

Therapeutic Concepts, PA

Houston, Texas, United States

Site Status

Institute of Tropical Medicine

Antwerp, , Belgium

Site Status

Saint-Pierre University Hospital

Brussels, , Belgium

Site Status

Hôpitaux IRIS SUD

Brussels, , Belgium

Site Status

Instituto Dominicano de Estudio Virologicos - IDEV

Santo Domingo, , Dominican Republic

Site Status

Salvador B Gautier Hospital, Infectious Diseases Department

Santo Domingo, , Dominican Republic

Site Status

Hôpital Bichat Claude Bernard

Paris, , France

Site Status

Hopital Tenon

Paris, , France

Site Status

Maladies Infectieuses Dpt

Paris, , France

Site Status

Hopitaux Universitaires Strasbourg

Strasbourg, , France

Site Status

Department of Health Sciences - University of Milan - San Paolo Hospital

Milan, , Italy

Site Status

Luigi Sacco Hospital, Milan

Milan, , Italy

Site Status

Clinica Malattie Infettive, Azienda Ospedaliero Universitaria

Modena, , Italy

Site Status

Hospital Civil de Guadalajara Dr Juan I Menchaca

Guadalajara, Jalisco, Mexico

Site Status

Hospital Civil de Guadalajara

Guadalajara, , Mexico

Site Status

Intituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Mexico City, , Mexico

Site Status

Hospital Fernando Fonseca

Amadora, , Portugal

Site Status

Hospital Dos Capuchos, Centro Hospitalar De Lisboa Central

Lisbon, , Portugal

Site Status

Hospital de Santa Maria - Serviço de Doenças Infecciosas

Lisbon, , Portugal

Site Status

centro Hospitalar S. João

Porto, , Portugal

Site Status

Centro Hospitalar do Porto - Hospital Joaquim Urbano

Porto, , Portugal

Site Status

Hospital de Santarém

Santarém, , Portugal

Site Status

Maternal Infants Studies Center (CEMI)

San Juan, , Puerto Rico

Site Status

Republic of Altay Center for Prevention and Control of AIDS and Infectious Diseases

Barnaul, , Russia

Site Status

GUZ "Irkutsk Regional Center for Prevention and Control of AIDS and Infectious Diseases

Irkutsk, , Russia

Site Status

Khabarovsk Territorial Center for Prevention and Control of AIDS and Infectious Diseases

Khabarovsk, , Russia

Site Status

"Infectious Diseases Center", LLC

Koltsovo, , Russia

Site Status

State Budget Healthcare Institution "Clinical Centre for AIDS and Infectious Diseases Fight and Prevention" of Krasnodar regio Department for Healthcare

Krasnodar, , Russia

Site Status

GUZ "Krasnoyarsk Territorial Center for Prevention and Control of AIDS and Infectious Diseases"

Krasnoyarsk, , Russia

Site Status

GUZ "Lipetsk Regional Center for Prevention and Control of AIDS and Infectious Diseases"

Lipetsk, , Russia

Site Status

Infectious Hospital 2

Moscow, , Russia

Site Status

State Healthcare Institution Infectious Clinical Hospital #2 of Moscow City Healthcare Department

Moscow, , Russia

Site Status

GKUZ MO "Center for Prevention and Treatment of AIDS and Infectious Diseases" (Moscow Regional AIDS Center)

Moscow, , Russia

Site Status

State Budget Health Institution of Nizhniy Novgorod "Nizhniy Novgorod Regional Center of prophylaxis and treatment of AIDS and Infectious Diseases

Nizhny Novgorod, , Russia

Site Status

Budgetary Medical Facility of the Orel Region "Orel Regional Center for Prevention and Control of AIDS and Infectious Diseases"

Oryol, , Russia

Site Status

Perm Regional Center for Prevention and Control of AIDS and Infectious Diseases

Perm, , Russia

Site Status

St.Petersburg Center for Prevention and Control of AIDS and Infectious Diseases, In-patient Department

Saint Petersburg, , Russia

Site Status

St.Petersburg GUZ "Center for Prevention and Control of AIDS and Infectious Diseases", Out-patient Department

Saint Petersburg, , Russia

Site Status

Saint-Petersburg GUZ "Clinical Infectious Hospital named after S.P.Botkin"

Saint Petersburg, , Russia

Site Status

Federal State Budgetary Institution "Republic Clinical Infectious Hospital"

Saint Petersburg, , Russia

Site Status

Saratov Regional Centre for Treatment and Prevention of AIDS and Infectious Diseases

Saratov, , Russia

Site Status

Volgograd Regional Center for Prevention and Control of AIDS and Infectious Diseases

Volgograd, , Russia

Site Status

GUZ "Voronezh Regional Center for Prevention and Control of AIDS and Infectious Diseases"

Voronezh, , Russia

Site Status

Sverdlovsk Regional Center for Prevention and control of AIDS and Infectious Diseases

Yekaterinburg, , Russia

Site Status

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)

Bangkok, , Thailand

Site Status

Faculty of Medicine Ramathibodi Hospital, Mahidol University

Bangkok, , Thailand

Site Status

Department of Preventive and Social Medicine, Faculty of Medicine, Siriraj Hospital

Bangkok, , Thailand

Site Status

Chiang Mai University

Chiang Mai, , Thailand

Site Status

Bamrasnaradura lnfectious Disease Institute

Nonthaburi, , Thailand

Site Status

Joint Clinical Research Centre

Kampala, , Uganda

Site Status

Barts Healthe NHS Trust

London, , United Kingdom

Site Status

Homerton University Hospital NHS Foundation Trust

London, , United Kingdom

Site Status

Royal Free London NHS Foundation Trust

London, , United Kingdom

Site Status

Queen Elizabeth Hospital, South London Healthcare NHS Trust

London, , United Kingdom

Site Status

Kings College London

London, , United Kingdom

Site Status

St George's Healthcare NHS Trust

London, , United Kingdom

Site Status

Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status

Mortimer Market Centre and Central and North West London NHS Foundation Trust

London, , United Kingdom

Site Status

Royal Berkshire NHS Foundation Trust

Reading, , United Kingdom

Site Status

Countries

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United States Belgium Dominican Republic France Italy Mexico Portugal Puerto Rico Russia Thailand Uganda United Kingdom

References

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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.

Reference Type RESULT
PMID: 27562742 (View on PubMed)

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.

Reference Type RESULT

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.

Reference Type RESULT

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.

Reference Type RESULT

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.

Reference Type RESULT

Other Identifiers

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2012-003708-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-236-0128

Identifier Type: -

Identifier Source: org_study_id

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