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

NCT01705574 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-236-01282012-003708-11
• Study Type: interventional
• Target: 583
• Locations: 12 countries
• Sites: 99

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.

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Keywords

HIV-1; HIV; Treatment-Naive; Women; WAVES

Outcome Measures

Primary Outcomes (1)

• 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

  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 Outcomes (4)

• Change From Baseline in CD4+ Cell Count at Week 48 of the Double-Blind Phase

  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

  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

  Open-Label Extension Week 48

• Change in CD4+ Cell Count at Week 48 of the Open-Label Extension Phase

  Baseline; Open-Label Extension Week 48

Study Arms (3)

E/C/F/TDF

EXPERIMENTAL

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

Drug: E/C/F/TDF; Drug: ATV Placebo; Drug: RTV Placebo; Drug: FTC/TDF Placebo

ATV + RTV+ FTC/TDF

ACTIVE COMPARATOR

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

Drug: ATV; Drug: RTV; Drug: FTC/TDF; Drug: E/C/F/TDF Placebo

Open-Label Extension Phase

EXPERIMENTAL

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; Drug: ATV; Drug: RTV; Drug: FTC/TDF; Drug: E/C/F/TAF

Interventions

E/C/F/TDF DRUG

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

Also known as: Stribild®

E/C/F/TDF; Open-Label Extension Phase

ATV DRUG

300 mg capsule administered orally with food once daily

Also known as: Reyataz®

ATV + RTV+ FTC/TDF; Open-Label Extension Phase

RTV DRUG

100 mg tablet administered orally with food once daily

Also known as: Norvir®

ATV + RTV+ FTC/TDF; Open-Label Extension Phase

FTC/TDF DRUG

200/300 mg tablet administered orally with food once daily

Also known as: Truvada®

ATV + RTV+ FTC/TDF; Open-Label Extension Phase

E/C/F/TDF Placebo DRUG

Tablet administered orally with food once daily

ATV + RTV+ FTC/TDF

ATV Placebo DRUG

Tablet administered orally with food once daily

E/C/F/TDF

RTV Placebo DRUG

Capsule administered orally with food once daily

E/C/F/TDF

FTC/TDF Placebo DRUG

Tablet administered orally with food once daily

E/C/F/TDF

E/C/F/TAF DRUG

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

Also known as: Genvoya®

Open-Label Extension Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (99)

University of Southern California AIDS Clinical Trials Group

Los Angeles, California, 90033, United States

Location

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

Whitman-Walker Health

Washington D.C., District of Columbia, 20009, United States

Location

George Washington University Medical Faculty Associates

Washington D.C., District of Columbia, 20037, United States

Location

Midway Immunology and Research Center

Ft. Pierce, Florida, 34982, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

IDOCF/ValuhealthMD

Orlando, Florida, 32806, United States

Location

St. Joseph's Hospital Comprehensive Research Institute

Tampa, Florida, 33614, United States

Location

Triple O Research Institute, P.A.

West Palm Beach, Florida, 33401, United States

Location

AIDS Research Consortium of Atlanta

Atlanta, Georgia, 30308, United States

Location

Emory HIV/AIDS Clinical Trials Unit

Atlanta, Georgia, 30308, United States

Location

Infectious Disease Specialists of Atlanta

Decatur, Georgia, 30033, United States

Location

Mercer University Mercer Medicine

Macon, Georgia, 31201, United States

Location

Chatham County Health Daprtment

Savannah, Georgia, 31401, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

LSUHSC HIV Out-Patient Clinic Research

New Orleans, Louisiana, 70119, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

The Research Institute

Springfield, Massachusetts, 01105, United States

Location

Saint Michael's Medical Center

Newark, New Jersey, 07102, United States

Location

New Jersey Medical School

Newark, New Jersey, 07103, United States

Location

New York Hospital Queens

Flushing, New York, 01135, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Montefiore Medical Center

The Bronx, New York, 10040, United States

Location

University of North Carolina AIDS Clinical Trials Unit

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

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

Greenville, North Carolina, 27834, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Wexner Medical Center at the Ohio State University

Columbus, Ohio, 43210, United States

Location

The University of Toledo Medical Center

Toledo, Ohio, 43614, United States

Location

Lehigh Valley Health Network

Allentown, Pennsylvania, 18102, United States

Location

Philadelphia FIGHT

Philadelphia, Pennsylvania, 19107, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Temple University Hospital- Internal General Medicine

Philadelphia, Pennsylvania, 19140, United States

Location

The Miriam Hospital

Providence, Rhode Island, 02906, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Central Texas Clinical Research

Austin, Texas, 78705, United States

Location

UT - Physicians

Bellaire, Texas, 77401, United States

Location

AIDS Arms, Inc./Trinity Health & Wellness Center

Dallas, Texas, 75208, United States

Location

North Texas Infectious Diseases Consultants, PA

Dallas, Texas, 75208, United States

Location

Therapeutic Concepts, PA

Houston, Texas, 77004, United States

Location

Institute of Tropical Medicine

Antwerp, 2000, Belgium

Location

Saint-Pierre University Hospital

Brussels, 1000, Belgium

Location

Hôpitaux IRIS SUD

Brussels, 1050, Belgium

Location

Instituto Dominicano de Estudio Virologicos - IDEV

Santo Domingo, 10514, Dominican Republic

Location

Salvador B Gautier Hospital, Infectious Diseases Department

Santo Domingo, 10514, Dominican Republic

Location

Hôpital Bichat Claude Bernard

Paris, 75018, France

Location

Hopital Tenon

Paris, 75020, France

Location

Maladies Infectieuses Dpt

Paris, 75651, France

Location

Hopitaux Universitaires Strasbourg

Strasbourg, 67091, France

Location

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

Milan, 20142, Italy

Location

Luigi Sacco Hospital, Milan

Milan, 20157, Italy

Location

Clinica Malattie Infettive, Azienda Ospedaliero Universitaria

Modena, 41124, Italy

Location

Hospital Civil de Guadalajara Dr Juan I Menchaca

Guadalajara, Jalisco, 44340, Mexico

Location

Hospital Civil de Guadalajara

Guadalajara, 44280, Mexico

Location

Intituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Mexico City, 14000, Mexico

Location

Hospital Fernando Fonseca

Amadora, 2720-276, Portugal

Location

Hospital Dos Capuchos, Centro Hospitalar De Lisboa Central

Lisbon, 1200-110, Portugal

Location

Hospital de Santa Maria - Serviço de Doenças Infecciosas

Lisbon, 1649-035, Portugal

Location

centro Hospitalar S. João

Porto, 4200-319, Portugal

Location

Centro Hospitalar do Porto - Hospital Joaquim Urbano

Porto, 4369-004, Portugal

Location

Hospital de Santarém

Santarém, 2005-177, Portugal

Location

Maternal Infants Studies Center (CEMI)

San Juan, 00936, Puerto Rico

Location

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

Barnaul, 656010, Russia

Location

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

Irkutsk, 664043, Russia

Location

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

Khabarovsk, 680031, Russia

Location

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

Krasnodar, 350015, Russia

Location

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

Krasnoyarsk, 660049, Russia

Location

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

Lipetsk, 398043, Russia

Location

Infectious Hospital 2

Moscow, 105275, Russia

Location

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

Moscow, 105275, Russia

Location

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

Moscow, 129110, Russia

Location

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

Nizhny Novgorod, 603950, Russia

Location

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

Oryol, 302040, Russia

Location

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

Perm, 614000, Russia

Location

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

Saint Petersburg, 190020, Russia

Location

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

Saint Petersburg, 190103, Russia

Location

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

Saint Petersburg, 191167, Russia

Location

Federal State Budgetary Institution "Republic Clinical Infectious Hospital"

Saint Petersburg, 196645, Russia

Location

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

Saratov, 410009, Russia

Location

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

Volgograd, 400040, Russia

Location

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

Voronezh, 394065, Russia

Location

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

Yekaterinburg, 620102, Russia

Location

"Infectious Diseases Center", LLC

Коltsovo, 630559, Russia

Location

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

Bangkok, 10330, Thailand

Location

Faculty of Medicine Ramathibodi Hospital, Mahidol University

Bangkok, 10400, Thailand

Location

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

Bangkok, 10700, Thailand

Location

Chiang Mai University

Chiang Mai, 50200, Thailand

Location

Bamrasnaradura lnfectious Disease Institute

Nonthaburi, 11000, Thailand

Location

Joint Clinical Research Centre

Kampala, Uganda

Location

Barts Healthe NHS Trust

London, E11BB, United Kingdom

Location

Homerton University Hospital NHS Foundation Trust

London, E96SR, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, NW32QG, United Kingdom

Location

Queen Elizabeth Hospital, South London Healthcare NHS Trust

London, SE18 4QH, United Kingdom

Location

Kings College London

London, SE59RJ, United Kingdom

Location

St George's Healthcare NHS Trust

London, SW17 0QT, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, W21NY, United Kingdom

Location

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

London, WC1E 6JB, United Kingdom

Location

Royal Berkshire NHS Foundation Trust

Reading, RG1 5LE, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 27562742 RESULT

• 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.

  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.

  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.

  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.

  RESULT

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Atazanavir Sulfate; Ritonavir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cobicistat; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Tenofovir; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Pyridines; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

There were no limitations affecting the analysis or results.

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2012
• First Posted: October 12, 2012
• Study Start: October 24, 2012
• Primary Completion: February 9, 2015
• Study Completion: September 6, 2018
• Last Updated: September 20, 2019
• Results First Posted: March 10, 2016

Record last verified: 2019-09

Locations

FR (4); ME (3); TH (5); US (41); BE (3); IT (3); PT (6); RU (21); DO (2); PR (1); GB (9); UG (1)