Switching From a TDF-Containing Combination Regimen to a TAF-Containing Fixed Dose Combination (FDC) in Virologically-Suppressed, HIV-1 Positive Participants

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01815736
First received: March 19, 2013
Last updated: March 15, 2016
Last verified: March 2016
  Purpose
This study is to evaluate the non-inferiority of switching to a tenofovir alafenamide (TAF)-containing fixed dose combination (FDC) relative to maintaining tenofovir disoproxil fumarate (TDF)-containing combination regimens in virologically suppressed HIV-infected participants as determined by having HIV-1 RNA < 50 copies/mL at Week 48.

Condition Intervention Phase
HIV
HIV Infections
Drug: E/C/F/TAF
Drug: E/C/F/TDF
Drug: EFV/FTC/TDF
Drug: RTV
Drug: ATV
Drug: FTC/TDF
Drug: COBI
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3, Open-Label Study to Evaluate Switching From a TDF-Containing Combination Regimen to a TAF-Containing Combination Single Tablet Regimen (STR) in Virologically-Suppressed, HIV-1 Positive Subjects

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, 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.


Secondary Outcome Measures:
  • Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: Yes ]
    Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan. BMD is calculated as grams per square centimeter (g/cm^2); the mean (SD) percentage change is presented.

  • Percent Change From Baseline in Spine BMD at Week 48 [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: Yes ]
    Spine BMD was assessed by DXA scan. BMD is calculated as g/cm^2; the mean (SD) percentage change is presented.

  • Change From Baseline in Serum Creatinine at Week 48 [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Overall EFV-related Symptom Assessment Score at Week 48 [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: No ]

    The mean (SD) change of the overall EFV-related symptom assessment score is presented. The overall symptom score (ranging from 0 to 20) is the sum of the individual symptom scores ranging from 0 (no symptoms) to 4 (most severe symptoms) from the 5 EFV-related symptom assessments (dizziness, trouble sleeping, impaired concentration, sleepiness, and abnormal or vivid dream).

    EFV-Related Symptom Analysis Set: participants who received EFV/FTC/TDF as prior treatment, received at least 1 dose of study drug, and completed EFV-related symptom assessments at the baseline visit and at least 1 postbaseline visit.



Enrollment: 1443
Study Start Date: March 2013
Estimated Study Completion Date: January 2017
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: E/C/F/TAF
Participants will switch to E/C/F/TAF FDC tablet for up to 96 weeks in the Randomized Phase, and may continue treatment with E/C/F/TAF in the open-label Extension Phase.
Drug: E/C/F/TAF
Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) FDC tablet administered orally once daily
Other Name: Genvoya®
Active Comparator: Stay on Baseline Treatment Regimen (SBR)
Participants will stay on their baseline FTC/tenofovir disoproxil fumarate (TDF)-containing regimen (either E/C/F/TDF, EFV/FTC/TDF, RTV+ATV+FTC/TDF, or COBI+ATV+FTC/TDF) for up to 96 weeks in the Randomized Phase, and may switch to E/C/F/TAF in the open-label Extension Phase.
Drug: E/C/F/TDF
Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) (150/150/200/300 mg) FDC tablet administered orally once daily
Other Name: Stribild®
Drug: EFV/FTC/TDF
Efavirenz (EFV)/FTC/TDF (600/200/300 mg) FDC tablet administered orally once daily
Other Name: Atripla®
Drug: RTV
Ritonavir (RTV) 100 mg tablet administered orally once daily
Other Name: Norvir®
Drug: ATV
Atazanavir (ATV) 300 mg capsule administered orally once daily
Other Name: Reyataz®
Drug: FTC/TDF
Emtricitabine (FTC)/TDF (200/300 mg) tablet administered orally once daily
Other Name: Truvada®
Drug: COBI
Cobicistat (COBI) 150 mg tablet administered orally once daily
Other Names:
  • Tybost®
  • GS-9350

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
  • Currently receiving antiretroviral therapy consisting of E/C/F/TDF, EFV/FTC/TDF, RTV+ATV+FTC/TDF, or COBI+ATV+FTC/TDF for ≥ 6 consecutive months preceding the final visit in their earlier study
  • Completion of the Week 144 visit in studies GS-US-236-0102, GS-US-236-0103, GS-US-216-0114, or completion of the Week 96 visit in study GS-US-264-0110 (only participants on an EFV-based regimen), or completion of studies GS-US-236-0104, GS-US-216-0105
  • Plasma HIV-1 RNA concentrations at undetectable levels for at least 6 consecutive months prior to the screening visit and have HIV RNA < 50 copies/mL at the screening visit
  • Normal echocardiograph (ECG)
  • Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
  • Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of the normal range (ULN)
  • Direct bilirubin ≤ 1.5 x ULN
  • Adequate hematologic function
  • Serum amylase ≤ 5 × ULN
  • Females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 12 weeks following the last dose of study drug if receiving EFV/FTC/TDF regimen, and 30 days for those assigned to all other regimens.
  • 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
  • Female participants who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range
  • Age ≥ 18 years

Exclusion Criteria:

  • A new AIDS-defining condition diagnosed within the 30 days prior to screening
  • Hepatitis B surface antigen position
  • Hepatitis C antibody positive
  • Participants experiencing decompensated cirrhosis
  • Females who are breastfeeding
  • Positive serum pregnancy test
  • Have an 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
  • 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 dosing requirements
  • Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial
  • Participants receiving ongoing therapy with drugs not to be used with elvitegravir (EVG), COBI, FTC, TDF, ATV, RTV, EFV, and TAF or participants with any known allergies to the excipients of E/C/F/TDF, E/C/F/TAF, EFV/FTC/TDF, ATV, COBI, RTV, or FTC/TDF
  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: NCT01815736

  Show 168 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Scott McCallister, MD Gilead Sciences
  More Information

Publications:
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01815736     History of Changes
Other Study ID Numbers: GS-US-292-0109  2012-005114-20 
Study First Received: March 19, 2013
Results First Received: March 15, 2016
Last Updated: March 15, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
HIV
HIV 1 Infected
Virologically-Suppressed

Additional relevant MeSH terms:
HIV Infections
Tenofovir
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 21, 2016