Human Immunodeficiency Virus (HIV-1) Infection MedDRA version: 18.0 Level: LLT Classification code 10068341 Term: HIV-1 infection System Organ Class: 100000004862
Conditions
Interventions
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
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion 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) 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 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 from screening throu
Exclusion criteria
Exclusion criteria: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of E/C/F/TAF fixed dose combination (FDC) after switching from a stable regimen consisting of FTC/TDF or ABC/3TC plus a third antiretroviral agent in maintaining HIV-1 RNA < 50 copies/mL at Week 12 (using pure virologic response) in subjects harboring the archived NRTI resistance mutation M184V and/or M184I in HIV-1 reverse transcriptase; Secondary Objective: - To determine the safety and tolerability of E/C/F/TAF FDC in subjects switching from 2 NRTI plus third antiretroviral agent regimens - To evaluate the development of new resistance mutations in subjects who develop virologic failure after switching to E/C/F/TAF FDC - To determine the durability of efficacy at Weeks 24 and 48 in maintaining HIV-1 RNA < 50 copies/mL using pure virologic response (PVR) ;Primary end point(s): The proportion of subjects with HIV-1 RNA <50 copies/mL at Week 12 as defined by pure virologic response.;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Emergence of new mutations in HIV-1 reverse transcriptase and integrase (attempted on any post Day 1 sample with HIV-1 RNA ? 50 copies/mL) 2) HIV-1 RNA< 50 copies/mL at Weeks 24 and 48 using PVR 3) HIV-1 RNA < 50 copies/mL at Weeks 12, 24 and 48 using the FDA snapshot analysis (sensitivity analysis) 4) CD4+ cell count change from Day 1 at Weeks 12, 24 and 48 ; Timepoint(s) of evaluation of this end point: 1) at any time post day 1 2) at Weeks 24 and 48 3) at Weeks 12, 24 and 48 4) at Weeks 12, 24 and 48 | — |
Countries
Germany, Spain
Contacts
Public ContactClinical Trials Mailbox
Gilead Sciences International Ltd.
Outcome results
None listed