A study to test the safety, tolerability and ability to maintain HIV suppression of switching from a tenofovir disoproxil fumarate (TDF) containing regimen to elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) in the HIV-1 infected subjects aged = 60 years who are virologically suppressed.

Phase 1

Conditions: Human Immunodeficiency Virus (HIV-1) Infection
MedDRA version: 19.0Level: LLTClassification code 10068341Term: HIV-1 infectionSystem Organ Class: 100000004862
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2015-002712-32-GB

Lead Sponsor: Gilead Sciences, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 150

Inclusion Criteria

1) The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
2) Age = 60 years
3) Currently receiving a TDF and FTC or 3TC-containing 'backbone' (maximum 2 NRTIs) regimen plus a third agent for = 6 consecutive months prior to screening visit. For subjects with 3 or more ART regimens, a regimen history must be provided for approval by the Sponsor.
4) Documented plasma HIV-1 RNA levels < 50 copies/mL for = 6 months preceding the screening visit
5) Plasma HIV-1 RNA level < 50 copies/mL at screening visit
6) Adequate renal function: Estimated glomerular filtration rate = 30 mL/min according to the Cockcroft-Gault formula
(eGFRCG) and are on ARVs that are appropriately dose adjusted for renal function per package insert
7) All documented historical plasma genotype(s) must not show resistance to TDF or FTC, including, but not limited to the presence of reverse transcriptase resistance mutations K65R, K70E, M184V/I or thymidine analog-associated mutations (TAMs) that include M41L, L210W, D67N, K70R, T215Y/F, K219Q/E/N/R. If historical plasma genotype prior to first ART is not available or subject has 3 or more ART regimens, subject will have proviral genotype analysis prior to Day 1 to confirm absence of archived resistance to TDF or FTC.
8) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
9) Hepatic transaminases (AST and ALT) = 5 × upper limit of normal (ULN)
10) Total bilirubin = 1.5 mg/dL and normal direct bilirubin (subjects with documented Gilbert’s syndrome or with atazanavir-associated hyperbilirubinemia may have total bilirubin up to 5 × ULN as long as direct bilirubin is normal)
11) Adequate hematologic function
- Absolute neutrophil count = 1,000/mm3
- Platelets = 50,000/mm3
- Hemoglobin = 8.5 g/dL
12) Study performed DXA scan and T-score received prior to Day 1
13) Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence, and agree to refrain from sperm donation from first dose throughout the study period and for 30 days following the last dose of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75

Exclusion Criteria

1) Previous use of any approved or experimental integrase strand transfer inhibitor (INSTI) (for any length of time) if the current regimen contains a PI/r
2) Subjects will have no evidence of previous virologic failure on a PI/r or INSTI-based regimen (with or without resistance to either class of ARV).
3) A new AIDS-defining condition diagnosed within the 30 days prior to screening (except CD4+ cell count and/or percentage criteria)
4) Hepatitis C virus that would require therapy during the study
5) Subjects with clinical evidence of decompensated cirrhosis (ascites, encephalopathy, variceal bleeding)
6) Women of childbearing potential
7) Subjects receiving ongoing treatment for bone disease (eg, osteoporosis), including bisphosphonates, denosumab, and strontium ranelate
8) Have an implanted defibrillator or pacemaker
9) Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
10) 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. Subjects with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Day 1 visit and must not be anticipated to require systemic therapy during the study
11) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 Visit
12) 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
13) Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial
14) Known hypersensitivity to the study drug, the metabolites, or formulation excipients
15) Subjects receiving ongoing therapy with any of the medications in Table 4-2 of the protocol, including drugs not to be used due to the potential for interaction with EVG, COBI, FTC, TAF, or 3TC; or subjects with any known allergies to the excipients of E/C/F/TAF FDC tablets.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: -To evaluate the safety of E/C/F/TAF relative to unchanged current antiretroviral therapy (ART) by assessing spine and hip bone mineral density (BMD) measured at Week 48 in virologically-suppressed, HIV-1 infected subjects aged = 60 years;Secondary Objective: - To evaluate spine and hip BMD at Week 24<br>- To evaluate maintenance of HIV-1 RNA suppression < 50 copies/mL between regimens at Weeks 24 and 48<br>- To evaluate the safety and tolerability of the two treatment groups through Week 48;Primary end point(s): Percent change from Baseline to Week 48 in spine and hip BMD;Timepoint(s) of evaluation of this end point: Week 48

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1) Percent change from baseline to Week 24 in spine and hip BMD<br>2) Proportion of subjects with HIV-1 RNA < 50 copies/mL at Weeks 24 and 48 as defined by the Food and Drug Administration (FDA) snapshot algorithm<br>3) Change from baseline in CD4+ cell count at Weeks 24 and 48;Timepoint(s) of evaluation of this end point: 1) Week 24<br>2) & 3) Weeks 24 and 48