Study to Evaluate Switching From Regimens Consisting of a Nonnucleoside Reverse Transcriptase Inhibitor Plus Emtricitabine and Tenofovir DF to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed, HIV-1 Infected Patients

• ClinicalTrials.gov Identifier: NCT01495702
• Recruitment Status: Completed
• First Posted: December 20, 2011
• Results First Posted: January 26, 2015
• Last Update Posted: January 7, 2016
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: December 14, 2011
• First Posted Date: December 20, 2011
• Results First Submitted Date: December 31, 2014
• Results First Posted Date: January 26, 2015
• Last Update Posted Date: January 7, 2016
• Study Start Date: December 2011
• Actual Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 22, 2015)

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 [ Time Frame: Week 48 ]

The FDA-defined 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.

Original Primary Outcome Measures (submitted: December 16, 2011)

The proportion of subjects who have HIV 1 RNA < 50 copies/mL at Week 48 [ Time Frame: 48 Weeks ]

The primary efficacy endpoint is the proportion of subjects who have HIV 1 RNA < 50 copies/mL at Week 48

Current Secondary Outcome Measures (submitted: December 1, 2015)

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 [ Time Frame: Week 96 ]
  The FDA-defined 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.
• Change From Baseline in CD4+ Cell Count at Week 48 [ Time Frame: Baseline; Week 48 ]
• Change From Baseline in CD4+ Cell Count at Week 96 [ Time Frame: Baseline; Week 96 ]

Original Secondary Outcome Measures (submitted: December 16, 2011)

To evaluate the change in CD4 cell count [ Time Frame: 48 Weeks ]

To evaluate the change in CD4 cell count in each treatment arm at 48 weeks

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

Descriptive Information

• Brief Title: Study to Evaluate Switching From Regimens Consisting of a Nonnucleoside Reverse Transcriptase Inhibitor Plus Emtricitabine and Tenofovir DF to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed, HIV-1 Infected Patients
• Official Title: A Phase 3b Randomized, Open Label Study to Evaluate Switching From Regimens Consisting of a Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) Plus Emtricitabine (FTC) and Tenofovir DF (TDF) to the Elvitegravir/Cobicistat/ Emtricitabine/Tenofovir Disoproxil Fumarate Single-Tablet Regimen (EVG/COBI/FTC/TDF) in Virologically Suppressed, HIV 1 Infected Patients
• Brief Summary: This study will evaluate the noninferiority of Stribild® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF)) single-tablet regimen (STR) relative to regimens consisting of a nonnucleoside reverse transcriptase inhibitor (NNRTI) plus Truvada® (FTC/TDF) in maintaining HIV-1 RNA < 50 copies/mL at Week 48 in virologically suppressed, HIV-1 infected adults. This study will also evaluate the safety, tolerability, and efficacy of the two regimens through 96 weeks of treatment.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Acquired Immunodeficiency Syndrome
• HIV Infections

Intervention

• Drug: NNRTI
  NNRTI agents administered according to prescribing information; allowed NNRTIs include efavirenz (EFV), nevirapine, or rilpivirine.
• Drug: FTC/TDF
  FTC/TDF (200/300 mg) administered according to prescribing information
  Other Name: Truvada
• Drug: Stribild
  Stribild® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate; E/C/F/TDF) (150/150/200/300 mg) STR administered orally once daily with food

Study Arms

• Experimental: Stribild
  Participants will switch from their baseline treatment regimen to Stribild for up to 96 weeks, and may continue to receive Stribild in the extension phase.
  Intervention: Drug: Stribild
• Active Comparator: NNRTI+FTC/TDF
  Participants will stay on their baseline treatment regimen antiretroviral regimen consisting of an NNRTI plus FTC/TDF for up to 96 weeks, and may switch to Stribild in the extension phase.
  Interventions:

  • Drug: NNRTI
  • Drug: FTC/TDF
  • Drug: Stribild

Publications *

• Pozniak A, Flamm J, Antinori A, Bloch M, Ward D, Berenguer J, Cote P, Andreatta K, Garner W, Szwarcberg J, Nguyen-Cleary T, McColl DJ, Piontkowsky D. Switching to the single-tablet regimen of elvitegravir, cobicistat, emtricitabine, and tenofovir DF from non-nucleoside reverse transcriptase inhibitor plus coformulated emtricitabine and tenofovir DF regimens: Week 96 results of STRATEGY-NNRTI. HIV Clin Trials. 2017 Jul;18(4):141-148. doi: 10.1080/15284336.2017.1338844. Epub 2017 Jul 9.
• Pozniak A, Markowitz M, Mills A, Stellbrink HJ, Antela A, Domingo P, Girard PM, Henry K, Nguyen T, Piontkowsky D, Garner W, White K, Guyer B. Switching to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of non-nucleoside reverse transcriptase inhibitor with emtricitabine and tenofovir in virologically suppressed adults with HIV (STRATEGY-NNRTI): 48 week results of a randomised, open-label, phase 3b non-inferiority trial. Lancet Infect Dis. 2014 Jul;14(7):590-9. doi: 10.1016/S1473-3099(14)70796-0. Epub 2014 Jun 5.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 22, 2015): 439
• Original Estimated Enrollment (submitted: December 16, 2011): 420
• Actual Study Completion Date: December 2014
• Actual Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Ability to understand and sign a written informed consent form
• Be stable on the current formulation(s) of an antiretroviral regimen consisting of an NNRTI plus FTC/TDF for ≥ 6 consecutive months preceding the screening visit. This includes those who began a regimen with individual drug components and subsequently simplified to include a fixed-dose combination formulation of the same drugs.
• Be on the first or second antiretroviral regimen with documented undetectable plasma HIV 1 RNA levels for ≥ 6 months preceding the screening visit
• No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI) for any length of time
• Documented historical genotype prior to starting initial antiretroviral therapy showing no known resistance to TDF or FTC
• HIV RNA < 50 copies/mL at screening
• Normal ECG
• Hepatic transaminases ≤ 5 × the upper limit of the normal range (ULN)
• Total bilirubin ≤ 1.5 mg/dL
• Adequate hematologic function
• Serum amylase ≤ 5 × ULN
• Estimated glomerular filtration rate ≥ 70 mL/min
• Females of childbearing potential must agree to utilize protocol recommended contraception methods or be nonheterosexually active, practice sexual abstinence from screening throughout the duration of the study period and for 12 weeks for participants on EFV/FTC/TDF or efavirenz or 30 days for the rest of participants following the last dose of study drug
• Female participants 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
• Male participants must agree to utilize protocol-recommended methods of contraception during heterosexual intercourse or be nonheterosexually active, and practice sexual abstinence from the screening visit.
• Age ≥ 18 years

Exclusion Criteria:

• New AIDS-defining condition diagnosed within the 30 days prior to screening
• Females who are breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• Receiving drug treatment for hepatitis C, or those who are anticipated to receive treatment for hepatitis C during the course of the study
• Experiencing decompensated cirrhosis
• Have an implanted defibrillator or pacemaker
• Current alcohol or substance abuse that would interfere with compliance
• A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma. Persons with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of baseline and must not be anticipated to require systemic therapy during the study.
• Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
• Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study
• Receiving ongoing therapy with any of the medications, including drugs not to be used with elvitegravir, cobicistat, FTC, or TDF; or those with any known allergies to the excipients of E/C/F/TDF tablets, or FTC/TDF tablets
• No anticipated need to initiate drugs during the study that are contraindicated
• Receiving other investigational drugs
• Participation in any other clinical trial
• Any other clinical condition or prior therapy that would make the participant 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, France, Germany, Italy, Portugal, Puerto Rico, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT01495702
• Other Study ID Numbers: GS-US-236-0121; 2011-004963-56 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Director: Damian McColl; Gilead Sciences

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