Switch Study to Evaluate F/TAF in HIV-1 Positive Participants Who Are Virologically Suppressed on Regimens Containing FTC/TDF

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02121795
First received: April 22, 2014
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

This study will evaluate the efficacy and safety of switching from emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) fixed dose combination (FDC) to emtricitabine/tenofovir alafenamide (F/TAF) FDC versus maintaining a treatment regimen of FTC/TDF FDC in HIV-1 positive participants who are virologically suppressed on regimens containing FTC/TDF. Efficacy will be determined by the proportion of participants with HIV-1 RNA < 50 copies/mL at Week 48.

This study will consist of a 96 week double-blind treatment period. After Week 96, all participants will continue on blinded study drug treatment and attend visits every 12 weeks until treatment assignments are unblinded. All participants will return for an unblinding visit and will be given the option to receive open-label F/TAF and attend visits every 12 weeks until F/TAF is commercially available, or the sponsor terminates the F/TAF clinical development program.


Condition Intervention Phase
HIV-1 Infection
Drug: FTC/TDF
Drug: F/TAF
Drug: Allowed third antiretroviral agent
Drug: Placebo to match FTC/TDF
Drug: Placebo to match F/TAF
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Switch Study to Evaluate F/TAF in HIV-1 Positive Subjects Who Are Virologically Suppressed on Regimens Containing FTC/TDF

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Proportion of participants with HIV-1 RNA < 50 copies/mL as defined by the FDA snapshot analysis [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percent change from baseline in hip bone mineral density (BMD) [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
  • Percent change from baseline in spine BMD [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
  • Proportion of participants with HIV-1 RNA < 50 copies/mL as defined by the FDA snapshot analysis [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
  • Proportion of participants with HIV-1 RNA < 20 copies/mL as defined by the FDA snapshot analysis [ Time Frame: Weeks 48 and 96 ] [ Designated as safety issue: No ]
  • Change from baseline in CD4+ cell count [ Time Frame: Baseline to Weeks 48 and 96 ] [ Designated as safety issue: No ]
  • Percent change from baseline in hip and spine BMD [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 660
Study Start Date: May 2014
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: F/TAF
Participants will receive emtricitabine 200 mg/tenofovir alafenamide 10 mg or 25 mg (F/TAF) plus placebo to match FTC/TDF, while remaining on an allowed third antiretroviral agent of the participant's pre-existing treatment regimen, for 96 weeks. Dosing of F/TAF will be dependent on the third agent of the participants' pre-existing treatment regimen.
Drug: F/TAF
F/TAF FDC tablet administered orally once daily
Drug: Allowed third antiretroviral agent
An allowed third antiretroviral agent of the participant's pre-existing regimen may include one of the following: ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, ritonavir-boosted darunavir, efavirenz (as individual agent only), rilpivirine (as individual agent only), nevirapine, raltegravir, dolutegravir, and maraviroc.
Drug: Placebo to match FTC/TDF
Placebo to match FTC/TDF FDC tablets administered orally once daily
Active Comparator: FTC/TDF
Participants will receive emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (FTC/TDF) plus placebo to match F/TAF, while remaining on an allowed third antiretroviral agent of the participant's pre-existing treatment regimen, for 96 weeks.
Drug: FTC/TDF
FTC/TDF FDC tablets administered orally once daily
Other Name: Truvada®
Drug: Allowed third antiretroviral agent
An allowed third antiretroviral agent of the participant's pre-existing regimen may include one of the following: ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, ritonavir-boosted darunavir, efavirenz (as individual agent only), rilpivirine (as individual agent only), nevirapine, raltegravir, dolutegravir, and maraviroc.
Drug: Placebo to match F/TAF
Placebo to match F/TAF FDC tablets administered orally once daily

  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 regimen containing FTC/TDF in combination with one third agent for ≥ 6 consecutive months prior to screening.
  • Plasma HIV-1 RNA levels < 50 copies/mL for at least 6 months preceding the screening visit (measured at least twice using the same assay) and not experienced two consecutive HIV-1 RNA above detectable levels after achieving a confirmed (two consecutive) HIV-1 RNA below detectable levels on the current regimen in the past year.
  • Plasma HIV-1 RNA should be < 50 copies/mL at the screening visit.
  • Normal electrocardiogram (ECG)
  • Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × the upper limit of the normal range (ULN)
  • Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin (individuals with documented Gilbert's syndrome or with Atazanavir-associated hyperbilirubinemia may have total bilirubin up to 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 abstinence from screening throughout the duration of the study treatment and for 30 days following the last dose of the study drug.
  • Females 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.
  • Females 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.
  • Males must agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 30 days following the last study drug dose.

Exclusion Criteria:

  • A new AIDS-defining condition diagnosed within the 30 days prior to screening
  • Hepatitis C virus (HCV) antibody positive and HCV RNA detectable
  • Individuals experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
  • Individuals receiving ongoing treatment with bisphosphonate to treat bone disease (eg, osteoporosis)
  • 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 study compliance
  • A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma.
  • Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 Visit
  • Individuals receiving ongoing therapy with any of the medications not to be used with FTC, TAF, TDF or other antiretroviral third agents.
  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: NCT02121795

Contacts
Contact: Gilead Study Team GS-US-311-1089@gilead.com

  Show 85 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Martin Rhee, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02121795     History of Changes
Other Study ID Numbers: GS-US-311-1089, 2013-005138-39
Study First Received: April 22, 2014
Last Updated: August 11, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
European Union: European Medicines Agency
Italy: The Italian Medicines Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Belgium: Federal Agency for Medicines and Health Products, FAMHP

Keywords provided by Gilead Sciences:
HIV
HIV-1 Positive
Virologically-suppressed

Additional relevant MeSH terms:
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014