A study to test the safety, tolerability and ability to maintain HIVsuppression of of switching from a current regimen consisting ofabacavir/lamivudine (ABC/3TC) plus a third antiretroviral agent to theelvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF)fixed-dose combination (FDC) in the HIV-1 infected subjects who arevirologically suppressed.
- Conditions
- Human Immunodeficiency Virus (HIV-1) InfectionMedDRA version: 20.1Level: LLTClassification code 10068341Term: HIV-1 infectionSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2015-002711-15-IT
- Lead Sponsor
- GILEAD SCIENCES INCORPORATED
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 275
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. Subjects must be on their first or second ARV regimen. (Refer to Table Error! No text of specified style in document. 1, for allowed third agents of the current regimen).
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).
a)In the preceding 6 months prior to screening, one episode of blip” (HIV 1 RNA > 50 and < 400 copies/mL) is acceptable, only if HIV-1 RNA is < 50 copies/mL immediately before and after the blip”.
b)To determine virologic suppression in the preceding 6 months prior to screening, the lower limit of quantification (LLOQ) by the local HIV-1 RNA assay may be used, only if its LLOQ is greater than 50 copies/mL (eg., LLOQ of 75 copies/mL).
5)Plasma HIV-1 RNA level < 50 copies/mL at screening visit
6)Documented historical genotype prior to starting initial ARV therapy (ART) showing no known resistance to TDF or FTC, including, but not limited to the presence of reverse transcriptase resistance mutants K65R, M184V/I, or thymidine analog-associated mutations (TAMs) (TAMs are: M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R). If a historical genotype is not available, subject will have proviral genotype analysis for archived resistance at screening visit.
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 {2202}:
Male:(140 – age in years) × (wt in kg) ¿ CLcr (mL/min)
72 × (serum creatinine in mg/dL)
Female:(140 – age in years) × (wt in kg) × 0.85 ¿ CLcr (mL/min)
72 × (serum creatinine in mg/dL)
9)Hepatic transaminases (AST and ALT) = 5 × upper limit of normal (ULN)
10)Total bilirubin = 1.5 mg/dL, or normal direct bilirubin (subjects with documented Gilbert’s syndrome or with atazanavir-associated hyperbilirubinemia may have total bilirubin up to 5 × ULN)
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 (as defined in Error! Reference source not found.) and agrees to utilize the protocol specified method of contraception or be non-heterosexually active or practice sexual abstinence (as defined in Error! Reference source not found.) 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 f
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) (refer to Appendix 6)
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, including drugs not to be used due to the potential for interaction with 3TC, COBI, EVG, FTC, or TAF (for 3TC, COBI, EVG, or FTC refer to the individual agents’ Prescribing Information; for TAF refer to the E/C/F/TAF FDC Investigator’s Brochure); 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<br>continuing on a baseline regimen consisting of ABC/3TC plus a third<br>antiretroviral agent in maintaining HIV-1 RNA < 50 copies/mL at Week<br>24 (using FDA snapshot algorithm) in virologically suppressed, HIV-1<br>infected adult subjects;Secondary Objective: - To evaluate the proportion of subjects maintaining virological response<br>(defined as HIV-1 RNA < 50 copies/mL, FDA snapshot analysis) at<br>Weeks 12 and 48<br>- To evaluate changes from baseline in CD4+ cell counts at Weeks 24 and<br>48<br>- To evaluate the safety and tolerability of the two treatment groups<br>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<br>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