A study to test the safety, tolerability and how well viral suppression is maintained of switching to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed dose combination (FDC) in HIV-1 infected subjects who are virologically suppressed and harbor the archived isolated NRTI resistance mutation M184V/M184I.
- Conditions
- Human Immunodeficiency Virus (HIV-1) InfectionMedDRA version: 20.1 Level: LLT Classification code 10068341 Term: HIV-1 infection System Organ Class: 100000004862Therapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2015-002710-74-DE
- Lead Sponsor
- Gilead Sciences, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 100
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) Documented historical genotype report showing M184V and/or M184I (mixtures are acceptable) in reverse transcriptase. Subjects must not have any primary INSTI or primary PI resistance mutations present on historical genotype; NNRTI mutations are allowed. Proviral DNA test must not have additional exclusion resistance mutations against PIs, NRTIs and INSTIs.
- Part 1 (first 50 subjects): Historical genotype report must show M184V and/or M184I in reverse transcriptase WITHOUT any other NRTI resistance mutation (including thymidine analogue-associated mutations (TAMs) [TAMs are: M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E/N/R], K65R, T69 insertion and Q151M mutation complex [A62V, V75I, F77L, F116Y, Q151M].
- Part 2 (after the interim efficacy review – 50 subjects): Historical genotype report must show M184V and/or M184I in reverse transcriptase WITH or WITHOUT one or two thymidine analogue-associated mutations (TAMs) [TAMs are: M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E/N/R]. Evidence of K65R, T69 insertion and/or Q151M mutation complex [A62V, V75I, F77L, F116Y, Q151M] will not be eligible.
4) Currently receiving an antiretroviral regimen consisting of FTC/TDF or ABC/3TC in combination with one third antiretroviral agent for = 6 consecutive months preceding the Screening Visit.
5) Documented plasma HIV-1 RNA levels < 50 copies/mL for = 6 months preceding the screening visit (measured at least twice using the same assay).
6) Plasma HIV-1 RNA levels < 50 copies/mL at Screening Visit
7) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
8) Estimated GFR = 30 mL/min according to the Cockcroft-Gault formula 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) 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)
c) Female subjects who have stopped menstruating for = 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory Reference range.
d) Of childbearing potential and agrees to utilize the protocol specified method of contraception or be non-heterosexually active or practice sexual abstinence
1) 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). Subjects may have evidence of prior virologic failure on only an NNRTI plus 2 NRTI-based regimen.
2) Subjects on a current PI/r-based regimen will have no evidence of previous use of any approved or experimental integrase strand transfer inhibitor (INSTI) (for any length of time).
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 infection that would require therapy during the study
5) Hepatitis B surface antigen (HBsAg) positive
6) Subjects with clinical evidence of decompensated cirrhosis (e.g., ascites, encephalopathy, variceal bleeding, etc.)
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 1 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) Subjects receiving ongoing therapy with any of the medications in Table 4-2 and those listed in Section 5.4 of the protocol, including drugs not to be used with EVG, COBI, 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
- Secondary Outcome Measures
Name Time Method