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

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: April 21, 2014
Last verified: April 2014
  Purpose

This randomized, open-label, active-controlled study is to evaluate the non-inferiority of switching to a tenofovir alafenamide (TAF)-Containing Combination single tablet regimen (STR) relative to maintaining tenofovir disoproxil fumarate (TDF)-containing combination regimens in virologically-suppressed HIV-1 positive subjects as determined by having HIV-1 RNA < 50 copies/mL at Week 48 following the switch.


Condition Intervention Phase
HIV
HIV Infections
Drug: E/C/F/TAF
Drug: E/C/F/TDF, EFV/FTC/TDF, ritonavir + atazanavir + FTC/TDF, or cobicistat + atazanavir + FTC/TDF
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 Regimens 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:
  • The proportion of participants who have HIV-1 RNA < 50 copies/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percent change from baseline in hip bone mineral density [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
  • Percent change from baseline in spine bone mineral density [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
  • Change from baseline in serum creatinine [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
  • Change from baseline in efavirenz-related symptom assessment score [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

Estimated Enrollment: 1500
Study Start Date: March 2013
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: E/C/F/TAF
Participants will switch to STR of E/C/F/TAF for 48 weeks
Drug: E/C/F/TAF
Single-tablet regimen of E/C/F/TAF containing elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg administered orally once daily
Active Comparator: E/C/F/TDF, EFV/FTC/TDF, ATV/r+FTC/TDF or ATV/co+FTC/TDF
Maintain pre-existing regimen [elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF), ritonavir-boosted atazanavir (ATV/r) + Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF), or cobicistat-boosted atazanavir (ATV/co) + FTC/TDF] for 48 weeks
Drug: E/C/F/TDF, EFV/FTC/TDF, ritonavir + atazanavir + FTC/TDF, or cobicistat + atazanavir + FTC/TDF
Other Names:
  • Stribild™ (E/C/F/TDF)
  • Atripla® (EFV/FTC/TDF)
  • Truvada® (FTC/TDF)

  Eligibility

Ages Eligible for Study:   18 Years and older
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, ATV/r + FTC/TDF, or ATV/co + 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 subjects on an efavirenz-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 mg/dL
  • 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 30 days following the last dose of study drug
  • Female subjects 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 subjects 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
  • Subjects 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
  • Subjects receiving ongoing therapy with drugs not to be used with elvitegravir (EVG), cobicistat (COBI), FTC, TDF, ATV, ritonavir (RTV), EFV, and TAF or subjects with any known allergies to the excipients of E/C/F/TDF STR, E/C/F/TAF STR, EFV/FTC/TDF, ATV, COBI, RTV, or FTC/TDF
  Contacts and Locations
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

No publications provided

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
Last Updated: April 21, 2014
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
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Emtricitabine
Ritonavir
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 April 23, 2014