A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Subjects on Chronic Hemodialysis

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2015-002713-30-AT
• Date of registration: 27/11/2015
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Subjects on Chronic Hemodialysis
• Scientific title: A Phase 3b Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Subjects on Chronic Hemodialysis
• Date of first enrolment: 12/01/2016
• Target sample size: 55
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002713-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, France, Germany, Puerto Rico, 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:
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study:
1) The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of screening procedures;
2) Age = 18 years;
3) Currently receiving a stable ARV regimen for = 6 consecutive months prior to screening;
4) Documented plasma HIV-1 RNA concentrations < 50 copies/mL for at least 6 months preceding the screening visit measured at least twice using the same assay) and have HIV-1 RNA < 50 copies/mL at screening; a) In the preceding 6 months prior to screening, one episode of “blip” (HIV-1 RNA = 50 copies/mL 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 (e.g. LLOQ of 75 copies/mL);
5 )No documented history of HIV-1 resistance to EVG, FTC, 3TC or TFV and no history of switching off EVG, FTC, 3TC or TFV due to concern for resistance;
6) CD4+ T cell count of = 200 cells/µL;
7) ESRD with eGFR < 15 mL/min by Cockcroft-Gault formula for creatinine clearance;
8) On chronic HD for = 6 months prior to screening;
9) Hepatic transaminases (AST and ALT) = 5 × upper limit of normal (ULN);
10) Chronic Hepatitis C (HCV) infection allowed if liver function is stable (see above for criteria);
11) Adequate hematologic function (absolute neutrophil count = 1,000/mm3; platelets = 50,000/mm3; hemoglobin = 8.5 g/dL);
12) Serum amylase = 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if serum lipase is = 5 × ULN);
13) 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 (unless permanently sterile or greater than two years post-menopausal); b) Of non-child bearing potential (i.e. 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. c) Of childbearing potential and agrees to utilize the protocol specified method of contraception or be non-heterosexually active or practice abstinence from screening throughout the duration of the study treatment and for 30 days following study drug discontinuation; d) Female subjects who utilize hormonal contraception as one of the birth control methods must have used the same method for at least three months prior to the study dosing.
14) Male subjects must agree to use protocol specified method(s) of contraception from screening throughout the duration of study treatment and for 30 days following discontinuation of study drugs.
15) Male subjects must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose.
16) Lactating females must agree to discontinue nursing before the study drug is administered.
Are the trial subjects under 18? no
Number of subjects for this age range:

Exclusion criteria:
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study :
1) Subjects experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.);
2) Hepatitis B surface antigen (HBsAg) positive;
3) Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening;
4) Treatment with radiation, cytotoxic chemotherapeutic agents, or any immunomodulator within 30 days of screening;
5) Any other clinical history, condition, or test result that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements;
6) Administration of other investigational agents (unless approved by Gilead Sciences). Participation in any other clinical trial, including observational trials, without prior approval from the sponsor is prohibited while participating in this trial.
7) History or presence of allergy or intolerance to the study drugs or their components;
8) A new AIDS-defining condition (excluding CD4+ T cell count and percentage criteria) diagnosed within the 30 days prior to screening, with the exception of oropharyngeal candidiasis;
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 carcinoma;
12) Received solid organ or bone marrow transplant;
13) Significant bone disease (e.g., osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochrondroses), or multiple bone fractures;
14) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1;
15) Systemic chemotherapeutic agents, systemic corticosteroids (except short-term use of prednisone as a steroid burst [ = 1 week of use]), immunosuppressant, or immunomodulating agents;
16) Subjects receiving ongoing therapy with any of the protocol listed medications, including drugs not to be used with EVG, COBI, FTC, TAF:


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

Health Condition(s) or Problem(s) studied

Human Immunodeficiency Virus (HIV-1) Infection in Subjects on Chronic Hemodialysis
MedDRA version: 19.1 Level: LLT Classification code 10068341 Term: HIV-1 infection System Organ Class: 100000004862

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

Intervention(s)

Product Name: elvitegravir/cobicistat/ emtricitabine/ tenofovir alafenamide
Product Code: E/C/F/TAF
Pharmaceutical Form: Film-coated tablet
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-
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: 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: EMTRICITABINE
CAS Number: 143491-57-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: To evaluate the safety and tolerability of the elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF; E/C/F/TAF) fixed dose combination (FDC) in HIV-1 infected adults with end stage renal disease (ESRD) on chronic hemodialysis (HD) at Week 48

Primary end point(s): Incidence of treatment-emergent grade 3 or higher adverse events up to Week 48.

Secondary Objective: -To evaluate the safety and tolerability of the EVG/COBI/FTC/TAF (E/C/F/TAF FDC) in HIV-1 infected adults with ESRD on chronic HD at week 96
- To evaluate the proportion of subjects achieving virologic response (HIV-1 RNA < 50 copies/mL, as defined by the FDA Snapshot analysis) at Weeks 24 and 48 and 96
- To evaluate plasma pharmacokinetics (PK) of EVG, COBI, FTC, TAF and TFV in HIV-1 infected patients with ESRD on chronic HD

Timepoint(s) of evaluation of this end point: Week 48

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1) up to Week 96
2) at Weeks 24, 48 and 96
3) At or between week 2 or week 4 on a day prior to the day of hemodialysis

Secondary end point(s): 1) Incidence of treatment-emergent grade 3 or higher adverse events up to Week 96
2) Proportion of subjects with HIV-1 RNA < 50 copies/mL at Weeks 24, 48, and 96 as defined by the FDA snapshot algorithm
3) The pharmacokinetics parameters of EVG, COBI, FTC, TAF and TFV, including AUCtau/AUClast, Cmax, and Cmin for the sub-study.

Secondary ID(s)

GS-US-292-1825

Source(s) of Monetary Support

Gilead Sciences, Inc.

Ethics review

Status: Approved
Approval date:
Contact: