Study to Evaluate the Safety and Efficacy of Stribild Versus Ritonavir-Boosted Atazanavir Plus Truvada in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults

• ClinicalTrials.gov Identifier: NCT01106586
• Recruitment Status: Completed
• First Posted: April 20, 2010
• Results First Posted: October 22, 2012
• Last Update Posted: November 11, 2015
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: April 14, 2010
• First Posted Date: April 20, 2010
• Results First Submitted Date: September 20, 2012
• Results First Posted Date: October 22, 2012
• Last Update Posted Date: November 11, 2015
• Study Start Date: April 2010
• Actual Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 23, 2014): The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48 [ Time Frame: Week 48 ]
• Original Primary Outcome Measures (submitted: April 19, 2010): The primary efficacy endpoint is the proportion of subjects that achieve HIV-1 RNA < 50 copies/mL at Week 48 [ Time Frame: 48 Weeks ]

Current Secondary Outcome Measures (submitted: October 9, 2015)

• The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 96 [ Time Frame: Week 96 ]
• The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 144 [ Time Frame: Week 144 ]
• The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 192 [ Time Frame: Week 192 ]
• The Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA-defined Time to Loss of Virologic Response (TLOVR) Algorithm [ Time Frame: Week 48 ]
• The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 [ Time Frame: Baseline; Weeks 48, 96, 144, and 192 ]
  Change = value of the relevant time point minus the baseline value
• The Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 [ Time Frame: Week 48 ]

Original Secondary Outcome Measures (submitted: April 19, 2010)

• The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 96 [ Time Frame: 96 Weeks ]
• The change from baseline in CD4+ cell count at Week 48 [ Time Frame: 48 Weeks ]
• The change from baseline in CD4+ cell count at Week 96 [ Time Frame: 96 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Safety and Efficacy of Stribild Versus Ritonavir-Boosted Atazanavir Plus Truvada in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults
• Official Title: A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 Versus Ritonavir-Boosted Atazanavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
• Brief Summary: To evaluate the safety and efficacy of Stribild®, a single tablet regimen (STR) containing fixed doses of elvitegravir (EVG)/cobicistat (COBI [GS-9350])/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus ritonavir-boosted atazanavir (ATV/r) plus the standard of care nucleoside reverse transcriptase inhibitor (NRTI) backbone FTC/TDF (Truvada®). ATV/r + FTC/TDF was selected as the active comparator for this study as it is a preferred protease inhibitor-based regimen in guidelines for the treatment of HIV-1 infected, antiretroviral treatment-naive adults.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• HIV
• HIV Infections

Intervention

• Drug: Stribild
  Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR administered orally once daily
• Drug: ATV
  Atazanavir 300 mg capsule administered orally once daily
• Drug: Ritonavir
  Ritonavir (RTV; /r) 100 mg tablet administered orally once daily
  Other Name: Norvir®
• Drug: FTC/TDF
  FTC/TDF 200/300 mg tablet administered orally once daily
  Other Name: Truvada
• Drug: Stribild Placebo
  Placebo to match Stribild administered orally once daily
• Drug: ATV Placebo
  Placebo to match ATV administered orally once daily
• Drug: RTV Placebo
  Placebo to match RTV administered orally once daily
• Drug: FTC/TDF Placebo
  Placebo to match FTC/TDF administered orally once daily

Study Arms

• Experimental: Stribild
  Interventions:

  • Drug: Stribild
  • Drug: ATV Placebo
  • Drug: RTV Placebo
  • Drug: FTC/TDF Placebo
• Active Comparator: ATV/r + FTC/TDF
  Interventions:

  • Drug: ATV
  • Drug: Ritonavir
  • Drug: FTC/TDF
  • Drug: Stribild Placebo

Publications *

• DeJesus E, Rockstroh JK, Henry K, Molina JM, Gathe J, Ramanathan S, Wei X, Yale K, Szwarcberg J, White K, Cheng AK, Kearney BP; GS-236-0103 Study Team. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet. 2012 Jun 30;379(9835):2429-2438. doi: 10.1016/S0140-6736(12)60918-0.
• Rockstroh JK, DeJesus E, Henry K, Molina JM, Gathe J, Ramanathan S, Wei X, Plummer A, Abram M, Cheng AK, Fordyce MW, Szwarcberg J; GS-236-0103 Study Team. A randomized, double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus coformulated emtricitabine and tenofovir DF for initial treatment of HIV-1 infection: analysis of week 96 results. J Acquir Immune Defic Syndr. 2013 Apr 15;62(5):483-6. doi: 10.1097/QAI.0b013e318286415c.
• Clumeck N, Molina JM, Henry K, Gathe J, Rockstroh JK, DeJesus E, Wei X, White K, Fordyce MW, Rhee MS, Szwarcberg J; GS-236-0103 Study Team. A randomized, double-blind comparison of single-tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus emtricitabine/tenofovir DF for initial treatment of HIV-1 infection: analysis of week 144 results. J Acquir Immune Defic Syndr. 2014 Mar 1;65(3):e121-4. doi: 10.1097/QAI.0000000000000089. No abstract available.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 12, 2011): 708
• Original Estimated Enrollment (submitted: April 19, 2010): 700
• Actual Study Completion Date: September 2014
• Actual Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
• Plasma HIV-1 RNA levels ≥ 5,000 copies/mL at screening
• No prior use of any approved or investigational antiretroviral drug for any length of time
• Screening genotype report must show sensitivity to FTC, TDF, and ATV
• Normal electrocardiogram (ECG)
• Adequate renal function (estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula)
• Hepatic transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 x the upper limit of the normal range (ULN)
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
• Adequate hematologic function
• Serum amylase ≤ 5 x ULN
• Males and Females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 days following the last dose of study drug
• Age ≥ 18 years
• Life expectancy ≥ 1 year

Exclusion Criteria:

• A new acquired immunodeficiency syndrome (AIDS)-defining condition diagnosed within the 30 days prior to screening
• Receiving drug treatment for hepatitis C, or anticipated to receive treatment for hepatitis C
• Subjects experiencing decompensated cirrhosis
• Females who are breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• Implanted defibrillator or pacemaker
• Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
• History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
• Medications contraindicated for use with EVG, COBI, FTC, TDF, ATV, or ritonavir or subjects with any known allergies to the excipients of Stribild tablets, Truvada tablets, ATV capsules or ritonavir tablets
• Participation in any other clinical trial without prior approval
• Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Canada, Denmark, France, Germany, Italy, Mexico, Netherlands, Portugal, Puerto Rico, Sweden, Switzerland, Thailand, United Kingdom, United States
• Removed Location Countries: Argentina, Brazil, Dominican Republic, Spain

Administrative Information

• NCT Number: NCT01106586
• Other Study ID Numbers: GS-US-236-0103
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Steven Chuck, VP, HIV Therapeutics, Gilead Sciences
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Marshall Fordyce, MD; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: October 2015