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.

• Register: EUCTR
• Last refreshed on: 19 February 2018
• Main ID: EUCTR2015-002711-15-ES
• Date of registration: 05/10/2015
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: 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.
• Scientific title: A Phase 3b, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Switching from Regimens 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 Virologically-Suppressed HIV-1 Infected Adult Subjects
• Date of first enrolment: 27/11/2015
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002711-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Delayed switch: pts. in treat. gp 2 (current regimen) switch to treat. gp 1 (ECFTAF FDC) after wk 24; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Italy, Spain, United Kingdom, United States

Contacts

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

Key inclusion & exclusion criteria

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. Subjects must be on their first or second ARV 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).
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
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 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 90 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) yes
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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Human Immunodeficiency Virus (HIV-1) Infection
MedDRA version: 18.0 Level: LLT Classification code 10068341 Term: HIV-1 infection System Organ Class: 100000004862

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Code: E/C/F/TAF 150mg/150mg/200mg/10mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Elvitegravir
CAS Number: 697761-98-1
Other descriptive name: ELVITEGRAVIR
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
INN or Proposed INN: COBICISTAT
CAS Number: 1004316-88-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
INN or Proposed INN: EMTRICITABINE
CAS Number: 143491-57-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: Tenofovir alafenamide
CAS Number: 379270-37-8
Other descriptive name: TENOFOVIR ALAFENAMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

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
- To evaluate changes from baseline in CD4+ cell counts at Weeks 24 and 48
- 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

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

Timepoint(s) of evaluation of this end point: Week 24

Secondary Outcome(s)

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
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
2) Weeks 24 and 48

Secondary ID(s)

2015-002711-15-GB

GS-US-292-1823

Source(s) of Monetary Support

Gilead Sciences, Inc.