A study to test the safety, tolerability and ability to maintain HIV suppression of of switching from a current regimen consisting of abacavir/lamivudine (ABC/3TC) plus a third antiretroviral agent to the elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) in the HIV-1 infected subjects 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: EUCTR2015-002711-15-DE

Lead Sponsor: Gilead Sciences, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 300

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 = 18 years
3) Currently receiving ABC/3TC plus a third antiretroviral (ARV) agent for = 6 consecutive months prior to the screening visit. For subjects with 3 or more ART regimens, a regimen history must be provided to the Sponsor for approval.
4) Documented plasma HIV-1 RNA levels < 50 copies/mL for = 6 months preceding the screening visit (measured at least twice using the same assay).
5) Plasma HIV-1 RNA level < 50 copies/mL at screening visit
6) 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 mutants K65R, K70E, M184V/I, or thymidine analog-associated mutations (TAMs) (TAMs are: M41L, D67N, K70R, L210W, 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.
7) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
8) Adequate renal function: Estimated GFR = 30 mL/min according to the Cockcroft-Gault formula (eGFRCG) for
creatinine clearance
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) A female subject is eligible to enter the study if it is confirmed that she is:
a) Not pregnant confirmed by a negative serum pregnancy test which is required for female subjects (unless permanently sterile or greater than two years post-menopausal).
b) Not nursing. Lactating females must agree to discontinue nursing before the study drug is administered.
c) Of non-childbearing potential (e.g., women who have had a hysterectomy, have had both ovaries removed or medically documented ovarian failure, or are postmenopausal women > 54 years of age with cessation (for = 12 months) of previously occurring menses).
d) Of childbearing potential and agrees to utilize the protocol specified method of contraception or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following discontinuation of study drugs.
e) 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.
13) Male subjects must agree to specified 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.
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 285
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 15

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) Positive Hepatitis B surface antigen (HBsAg)
6) Subjects with clinical evidence of decompensated cirrhosis (ascites, encephalopathy, variceal bleeding)
7) Females who are breastfeeding
8) Positive serum pregnancy test
9) Have an implanted defibrillator or pacemaker
10) Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
11) 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 1visit and must not be anticipated to require systemic therapy during the study.
12) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1
13) 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
14) Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial
15) Known hypersensitivity to the study drug, the metabolites, or formulation excipients
16) 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 3TC, COBI, EVG, FTC, or TAF; 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 efficacy of switching to E/C/F/TAF FDC relative to continuing on a baseline regimen consisting of ABC/3TC plus a third antiretroviral agent in maintaining HIV-1 RNA < 50 copies/mL at Week 24 (using FDA snapshot algorithm) in virologically suppressed, HIV-1 infected adult subjects;Secondary Objective: - To evaluate the proportion of subjects maintaining virological response (defined as HIV-1 RNA < 50 copies/mL, FDA snapshot analysis) at Weeks 12 and 48<br>- To evaluate changes from baseline in CD4+ cell counts at Weeks 24 and 48<br>- To evaluate the safety and tolerability of the two treatment groups over 24 and 48 weeks;Primary end point(s): Proportion of subjects with HIV-1 RNA <50 copies/mL at Week 24 as defined by the FDA snapshot algorithm;Timepoint(s) of evaluation of this end point: Week 24

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1) Proportion of subjects with HIV-1 RNA <50 copies/mL at Weeks 12 and 48 as defined by the FDA snapshot algorithm<br>2) The change from baseline in CD4+ cell counts at Weeks 24 and 48;Timepoint(s) of evaluation of this end point: 1) Weeks 12 and 48<br>2) Weeks 24 and 48