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 (WAVES)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01705574
First received: October 10, 2012
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

This double-blind, randomized, multicenter, active-controlled study is to evaluate the efficacy of a regimen containing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate single-tablet regiment versus ritonavir-boosted atazanavir plus emtricitabine/tenofovir disoproxil fumarate in HIV-1 infected, antiretroviral treatment-naive adult women as determined by the achievement of HIV 1 RNA < 50 copies/mL at Week 48 (end of the double-blind period).

Subjects initially randomized to the EVG/COBI/FTC/TDF arm will have the option to continue open-label EVG/COBI/FTC/TDF STR (after Week 60) for an additional 48 weeks during an open-label extension period. Subjects initially randomized to the RTV+ATV+FTC/TDF arm will have the option to be rerandomized in a 1:3 ratio to continue treatment with RTV+ATV+FTC/TDF or switch to EVG/COBI/FTC/TAF STR (after Week 60) for an additional 48 weeks during an open-label extension period.


Condition Intervention Phase
Acquired Immunodeficiency Syndrome
HIV Infections
Drug: EVG/COBI/FTC/TDF
Drug: RTV
Drug: ATV
Drug: FTC/TDF
Drug: EVG/COBI/FTC/TDF Placebo
Drug: RTV Placebo
Drug: ATV Placebo
Drug: FTC/TDF Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • The proportion of subjects with HIV 1 RNA < 50 copies/mL at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    The primary efficacy endpoint is the proportion of subjects with HIV 1 RNA <50 copies/mL at Week 48


Secondary Outcome Measures:
  • To evaluate the change in CD4+ cell count at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    The change from baseline in CD4+ cell count at Week 48


Estimated Enrollment: 510
Study Start Date: October 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EVG/COBI/FTC/TDF
EVG 150 mg/COBI 150mg/FTC 200 mg/TDF 300 mg STR plus placebos to match RTV, ATV, and FTC/TDF once daily
Drug: EVG/COBI/FTC/TDF
Elvitegravir (EVG) 150 mg/cobicistat (COBI) 150 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg single-tablet regimen administered orally with food once daily
Drug: RTV Placebo
Placebo to match RTV administered orally with food once daily
Drug: ATV Placebo
Placebo to match ATV administered orally with food once daily
Drug: FTC/TDF Placebo
Placebo to match FTC/TDF administered orally with food once daily
Active Comparator: RTV+ATV+FTC/TDF
RTV 100 mg plus ATV 300 mg plus FTC 200 mg/TDF 300 mg plus placebo to match EVG/COBI/FTC/TDF once daily
Drug: RTV
Ritonavir 100 mg tablet administered orally with food once daily
Other Name: Norvir®
Drug: ATV
Atazanavir (ATV) 300 mg capsule administered orally with food once daily
Other Name: Reyataz®
Drug: FTC/TDF
FTC 200 mg/TDF 300 mg tablet administered orally with food once daily
Other Name: Truvada®
Drug: EVG/COBI/FTC/TDF Placebo
Placebo to match EVG/COBI/FTC/TDF administered with food orally once daily
Experimental: EVG/COBI/FTC/TDF Open Label Switch
Participants randomized to the RTV+ATV+FTC/TDF arm switched to receive EVG/COBI/FTC/TDF in the open-label phase
Drug: EVG/COBI/FTC/TDF
Elvitegravir (EVG) 150 mg/cobicistat (COBI) 150 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg single-tablet regimen administered orally with food once daily
Drug: RTV
Ritonavir 100 mg tablet administered orally with food once daily
Other Name: Norvir®
Drug: ATV
Atazanavir (ATV) 300 mg capsule administered orally with food once daily
Other Name: Reyataz®
Drug: FTC/TDF
FTC 200 mg/TDF 300 mg tablet administered orally with food once daily
Other Name: Truvada®
Drug: EVG/COBI/FTC/TDF Placebo
Placebo to match EVG/COBI/FTC/TDF administered with food orally once daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 boosted with ritonavir (ATV/r)
  • 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
  • Subjects receiving drug treatment for Hepatitis C, or subjects who are anticipated to receive treatment for Hepatitis C during the course of the study
  • Subjects 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 subject 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 subject unsuitable for the study or unable to comply with the dosing requirements
  • Subjects receiving ongoing therapy with any disallowed medications, including drugs not to be used with EVG, COBI, FTC, TDF, ATV, RTV; or subjects with any known allergies to the excipients of EVG/COBI/FTC/TDF STR, Truvada® tablets, atazanavir capsules or ritonavir tablets
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01705574

  Show 99 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Huyen Cao, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01705574     History of Changes
Other Study ID Numbers: GS-US-236-0128, 2012-003708-11
Study First Received: October 10, 2012
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
HIV-1
HIV
Treatment-Naive
Women
WAVES

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Emtricitabine
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Ritonavir
Tenofovir
Tenofovir disoproxil
Atazanavir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014