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

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ClinicalTrials.gov Identifier: NCT01705574
Recruitment Status : Completed
First Posted : October 12, 2012
Results First Posted : March 10, 2016
Last Update Posted : October 30, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE October 10, 2012
First Posted Date  ICMJE October 12, 2012
Results First Submitted Date  ICMJE February 11, 2016
Results First Posted Date  ICMJE March 10, 2016
Last Update Posted Date October 30, 2018
Actual Study Start Date  ICMJE October 24, 2012
Actual Primary Completion Date February 11, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 11, 2016)
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 of the Double-Blind Phase [ Time Frame: Week 48 ]
The snapshot algorithm was used which defines a patient'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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 11, 2012)
The proportion of subjects with HIV 1 RNA < 50 copies/mL at Week 48 [ Time Frame: 48 Weeks ]
The primary efficacy endpoint is the proportion of subjects with HIV 1 RNA <50 copies/mL at Week 48
Change History Complete list of historical versions of study NCT01705574 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2016)
  • Change From Baseline in CD4+ Cell Count at Week 48 of the Double-Blind Phase [ Time Frame: Baseline; Week 48 ]
  • Percentage of Participants Receiving Open-Label E/C/F/TDF With HIV-1 RNA < 50 Copies/mL at Week 48 of the Open- Label Extension Phase [ Time Frame: Open-Label Extension Week 48 ]
    The snapshot algorithm was used which defines a patient'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.
  • Percentage of Participants Receiving E/C/F/TDF or ATV+RTV+FTC/TDF With HIV-1 RNA < 50 Copies/mL at Week 48 of the Open-Label Extension Phase [ Time Frame: 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2012)
To evaluate the change in CD4+ cell count at Week 48 [ Time Frame: 48 Weeks ]
The change from baseline in CD4+ cell count at Week 48
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of E/C/F/TDF (Stribild®) Versus RTV-Boosted ATV Plus FTC/TDF (Truvada®) in HIV-1 Infected, Antiretroviral Treatment-Naive Women
Official Title  ICMJE 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
Brief Summary

This study will evaluate the safety, efficacy, and tolerability of a regimen containing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (Stribild®; E/C/F/TDF) fixed-dose combination (FDC) versus ritonavir (RTV)-boosted atazanavir (ATV) plus emtricitabine/tenofovir disoproxil fumarate (Truvada®; FTC/TDF) in HIV-1 infected, antiretroviral treatment-naive adult women.

This study will consist of two phases: Double-Blinded Treatment Phase (48 weeks) and Open-Label Extension (OLE) Phase (48 weeks).

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 OLE Phase.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Acquired Immunodeficiency Syndrome
  • HIV Infections
Intervention  ICMJE
  • Drug: E/C/F/TDF
    E/C/F/TDF (150/150/200/300 mg) FDC tablet administered orally with food once daily
    Other Name: Stribild®
  • Drug: RTV
    RTV 100 mg tablet administered orally with food once daily
    Other Name: Norvir®
  • Drug: ATV
    ATV 300 mg capsule administered orally with food once daily
    Other Name: Reyataz®
  • Drug: FTC/TDF
    FTC/TDF (200/300 mg) tablet administered orally with food once daily
    Other Name: Truvada®
  • Drug: E/C/F/TDF Placebo
    E/C/F/TDF placebo tablet administered orally with food once daily
  • Drug: RTV Placebo
    RTV placebo tablet administered orally with food once daily
  • Drug: ATV Placebo
    ATV placebo capsule administered orally with food once daily
  • Drug: FTC/TDF Placebo
    FTC/TDF placebo tablet administered orally with food once daily
  • Drug: E/C/F/TAF
    E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally with food once daily
    Other Name: Genvoya®
Study Arms  ICMJE
  • Experimental: E/C/F/TDF
    E/C/F/TDF + ATV placebo + RTV placebo + FTC/TDF placebo
    Interventions:
    • Drug: E/C/F/TDF
    • Drug: RTV Placebo
    • Drug: ATV Placebo
    • Drug: FTC/TDF Placebo
  • Active Comparator: ATV+RTV+FTC/TDF
    ATV+RTV+FTC/TDF + E/C/F/TDF placebo
    Interventions:
    • Drug: RTV
    • Drug: ATV
    • Drug: FTC/TDF
    • Drug: E/C/F/TDF Placebo
  • Experimental: Open-Label Extension
    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 rerandomized to receive elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or ATV+RTV+FTC/TDF.
    Interventions:
    • Drug: E/C/F/TDF
    • Drug: RTV
    • Drug: ATV
    • Drug: FTC/TDF
    • Drug: E/C/F/TAF
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 20, 2015)
583
Original Estimated Enrollment  ICMJE
 (submitted: October 11, 2012)
510
Actual Study Completion Date  ICMJE September 6, 2018
Actual Primary Completion Date February 11, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Dominican Republic,   France,   Italy,   Mexico,   Portugal,   Puerto Rico,   Russian Federation,   Thailand,   Uganda,   United Kingdom,   United States
Removed Location Countries Brazil
 
Administrative Information
NCT Number  ICMJE NCT01705574
Other Study ID Numbers  ICMJE GS-US-236-0128
2012-003708-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP