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

HIV Infections Clinical Trial

— WAVES  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01705574
• Other study ID #: GS-US-236-0128
• Secondary ID: 2012-003708-11
• Status: Completed
• Phase: Phase 3
• Start date: October 24, 2012
• Est. completion date: September 6, 2018

Study information

• Verified date: September 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 583
• Est. completion date: September 6, 2018
• Est. primary completion date: February 9, 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes

Intervention

Drug:
• E/C/F/TDF
150/150/200/300 mg FDC tablet administered orally with food once daily
• ATV
300 mg capsule administered orally with food once daily
• RTV
100 mg tablet administered orally with food once daily
• FTC/TDF
200/300 mg tablet administered orally with food once daily
• E/C/F/TDF Placebo
Tablet administered orally with food once daily
• ATV Placebo
Tablet administered orally with food once daily
• RTV Placebo
Capsule administered orally with food once daily
• FTC/TDF Placebo
Tablet administered orally with food once daily
• E/C/F/TAF
150/150/200/10 mg FDC tablet administered orally with food once daily

Locations

Country	Name	City	State
Belgium	Institute of Tropical Medicine	Antwerp
Belgium	Hôpitaux IRIS SUD	Brussels
Belgium	Saint-Pierre University Hospital	Brussels
Dominican Republic	Instituto Dominicano de Estudio Virologicos - IDEV	Santo Domingo
Dominican Republic	Salvador B Gautier Hospital, Infectious Diseases Department	Santo Domingo
France	Hôpital Bichat Claude Bernard	Paris
France	Hopital Tenon	Paris
France	Maladies Infectieuses Dpt	Paris
France	Hopitaux Universitaires Strasbourg	Strasbourg
Italy	Department of Health Sciences - University of Milan - San Paolo Hospital	Milan
Italy	Luigi Sacco Hospital, Milan	Milan
Italy	Clinica Malattie Infettive, Azienda Ospedaliero Universitaria	Modena
Mexico	Hospital Civil de Guadalajara	Guadalajara
Mexico	Hospital Civil de Guadalajara Dr Juan I Menchaca	Guadalajara	Jalisco
Mexico	Intituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán	Mexico City
Portugal	Hospital Fernando Fonseca	Amadora
Portugal	Hospital de Santa Maria - Serviço de Doenças Infecciosas	Lisboa
Portugal	Hospital Dos Capuchos, Centro Hospitalar De Lisboa Central	Lisboa
Portugal	Centro Hospitalar do Porto - Hospital Joaquim Urbano	Porto
Portugal	centro Hospitalar S. João	Porto
Portugal	Hospital de Santarém	Santarem
Puerto Rico	Maternal Infants Studies Center (CEMI)	San Juan
Russian Federation	Republic of Altay Center for Prevention and Control of AIDS and Infectious Diseases	Barnaul
Russian Federation	Sverdlovsk Regional Center for Prevention and control of AIDS and Infectious Diseases	Ekaterinburg
Russian Federation	GUZ "Irkutsk Regional Center for Prevention and Control of AIDS and Infectious Diseases	Irkutsk
Russian Federation	Khabarovsk Territorial Center for Prevention and Control of AIDS and Infectious Diseases	Khabarovsk
Russian Federation	"Infectious Diseases Center", LLC	Koltsovo
Russian Federation	State Budget Healthcare Institution "Clinical Centre for AIDS and Infectious Diseases Fight and Prevention" of Krasnodar regio Department for Healthcare	Krasnodar
Russian Federation	GUZ "Krasnoyarsk Territorial Center for Prevention and Control of AIDS and Infectious Diseases"	Krasnoyarsk
Russian Federation	GUZ "Lipetsk Regional Center for Prevention and Control of AIDS and Infectious Diseases"	Lipetsk
Russian Federation	GKUZ MO "Center for Prevention and Treatment of AIDS and Infectious Diseases" (Moscow Regional AIDS Center)	Moscow
Russian Federation	Infectious Hospital 2	Moscow
Russian Federation	State Healthcare Institution Infectious Clinical Hospital #2 of Moscow City Healthcare Department	Moscow
Russian Federation	State Budget Health Institution of Nizhniy Novgorod "Nizhniy Novgorod Regional Center of prophylaxis and treatment of AIDS and Infectious Diseases	Nizhniy Novgorod
Russian Federation	Budgetary Medical Facility of the Orel Region "Orel Regional Center for Prevention and Control of AIDS and Infectious Diseases"	Orel
Russian Federation	Perm Regional Center for Prevention and Control of AIDS and Infectious Diseases	Perm
Russian Federation	Federal State Budgetary Institution "Republic Clinical Infectious Hospital"	Saint-Petersburg
Russian Federation	Saint-Petersburg GUZ "Clinical Infectious Hospital named after S.P.Botkin"	Saint-Petersburg
Russian Federation	St.Petersburg Center for Prevention and Control of AIDS and Infectious Diseases, In-patient Department	Saint-Petersburg
Russian Federation	St.Petersburg GUZ "Center for Prevention and Control of AIDS and Infectious Diseases", Out-patient Department	Saint-Petersburg
Russian Federation	Saratov Regional Centre for Treatment and Prevention of AIDS and Infectious Diseases	Saratov
Russian Federation	Volgograd Regional Center for Prevention and Control of AIDS and Infectious Diseases	Volgograd
Russian Federation	GUZ "Voronezh Regional Center for Prevention and Control of AIDS and Infectious Diseases"	Voronezh
Thailand	Department of Preventive and Social Medicine, Faculty of Medicine, Siriraj Hospital	Bangkok
Thailand	Faculty of Medicine Ramathibodi Hospital, Mahidol University	Bangkok
Thailand	The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)	Bangkok
Thailand	Chiang Mai University	Chiang Mai
Thailand	Bamrasnaradura lnfectious Disease Institute	Nonthaburi
Uganda	Joint Clinical Research Centre	Kampala
United Kingdom	Barts Healthe NHS Trust	London
United Kingdom	Homerton University Hospital NHS Foundation Trust	London
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	Kings College London	London
United Kingdom	Mortimer Market Centre and Central and North West London NHS Foundation Trust	London
United Kingdom	Queen Elizabeth Hospital, South London Healthcare NHS Trust	London
United Kingdom	Royal Free London NHS Foundation Trust	London
United Kingdom	St George's Healthcare NHS Trust	London
United Kingdom	Royal Berkshire NHS Foundation Trust	Reading
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	AIDS Research Consortium of Atlanta	Atlanta	Georgia
United States	Emory HIV/AIDS Clinical Trials Unit	Atlanta	Georgia
United States	Central Texas Clinical Research	Austin	Texas
United States	UT - Physicians	Bellaire	Texas
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	University of North Carolina AIDS Clinical Trials Unit	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Wexner Medical Center at the Ohio State University	Columbus	Ohio
United States	AIDS Arms, Inc./Trinity Health & Wellness Center	Dallas	Texas
United States	North Texas Infectious Diseases Consultants, PA	Dallas	Texas
United States	Infectious Disease Specialists of Atlanta	Decatur	Georgia
United States	Duke University Medical Center	Durham	North Carolina
United States	New York Hospital Queens	Flushing	New York
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	East Carolina University The Brody School of Medicine Div. of Infectious Diseases	Greenville	North Carolina
United States	Therapeutic Concepts, PA	Houston	Texas
United States	University of Southern California AIDS Clinical Trials Group	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Mercer University Mercer Medicine	Macon	Georgia
United States	University of Miami	Miami	Florida
United States	LSUHSC HIV Out-Patient Clinic Research	New Orleans	Louisiana
United States	New Jersey Medical School	Newark	New Jersey
United States	Saint Michael's Medical Center	Newark	New Jersey
United States	IDOCF/ValuhealthMD	Orlando	Florida
United States	Orlando Immunology Center	Orlando	Florida
United States	Philadelphia FIGHT	Philadelphia	Pennsylvania
United States	Temple University Hospital- Internal General Medicine	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	The Miriam Hospital	Providence	Rhode Island
United States	University of Rochester	Rochester	New York
United States	University of California, Davis Medical Center	Sacramento	California
United States	Chatham County Health Daprtment	Savannah	Georgia
United States	The Research Institute	Springfield	Massachusetts
United States	St. Joseph's Hospital Comprehensive Research Institute	Tampa	Florida
United States	The University of Toledo Medical Center	Toledo	Ohio
United States	George Washington University Medical Faculty Associates	Washington	District of Columbia
United States	Whitman-Walker Health	Washington	District of Columbia
United States	Triple O Research Institute, P.A.	West Palm Beach	Florida
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Belgium,  Dominican Republic,  France,  Italy,  Mexico,  Portugal,  Puerto Rico,  Russian Federation,  Thailand,  Uganda,  United Kingdom, 

References & Publications (5)

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.

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-nai

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 a

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-nai

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, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change From Baseline in CD4+ Cell Count at Week 48 of the Double-Blind Phase		Baseline; Week 48
Secondary	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	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
Secondary	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	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
Secondary	Change in CD4+ Cell Count at Week 48 of the Open-Label Extension Phase		Baseline; Open-Label Extension Week 48