Elvucitabine, a novel nucleoside analog, is being studied as a treatment for participants with human immunodeficiency virus (HIV)-1. This Phase 2 study will enroll 60 HIV-1-naive participants to assess the efficacy and safety of elvucitabine compared to lamivudine in combination with tenofovir and efavirenz as measured by changes in the participant's HIV-ribonucleic acid (RNA) level and CD4 cell count. The study treatment will be 12 weeks of blinded study medication followed by an additional 84 weeks of open-label treatment if the participant's response to treatment meets certain endpoints. The pharmacokinetics of elvucitabine will also be assessed during the study.
Sixty HIV-1-infected, clinically stable, treatment-naïve adults with no acquired immunodeficiency syndrome (AIDS)-defining events during the 3 months prior to screening will be randomly assigned to 1 of 2 treatment groups. Participant plasma HIV-1 RNA levels must be greater than or equal to 5000 copies/millimeter (mL), and CD4 cell counts must be greater than 200 cells/mL and less than 500 cells/mL at Screening. Participants must be sensitive to elvucitabine, lamivudine, and emtricitabine as demonstrated by the absence of the M184V, M184I, and D237E mutations by TRUGENE HIV-1 Genotyping Kit. Participants must be genotypically sensitive to efavirenz (negative for K103 or Y188L mutations) and tenofovir (negative for K65R mutation) as demonstrated by TRUGENE HIV-1 Genotyping Kit. They must have acceptable hematologic and chemistry parameters. Participants whose HIV-1 RNA levels have decreased at least 2 logs or to below 400 copies/mL by Week 10 may be considered eligible to enter the extension phase of up to 36 weeks of additional treatment. Participants in the extension phase will be evaluated at Weeks 14 and 16 and every 4 Weeks until Week 96. Once all participants have completed 12 weeks of treatment, and the data are available for all visits through Week 12, the database will be locked and the treatment assignments will be unblinded. Any participant who has had less than 48 weeks of treatment will be allowed to continue on the same treatment as initially assigned on an open-label basis through 48 weeks. All participants will have 2 post-treatment follow-up visits, at 1 and 4 weeks after the end of treatment. Concentrations of elvucitabine in the plasma will be measured on Day 1, at Weeks 4, 6, 8, 12, 16, 24, 48, 72, 96, and at Follow-up Efficacy will be assessed by measuring plasma HIV-1 RNA levels and CD4 counts at each study visit. Safety evaluation will include vital signs, physical examinations, electrocardiograms, assessments of adverse events (AEs), measurement of plasma HIV-1 RNA levels and CD4 counts, determination of HIV-1 genotype at Screening and at Weeks 12, 24, 48, and 96, determination of HIV-1 phenotype at Visit 1 and at Weeks 12, 24, 48, and 96 urine and serum pregnancy tests, as well as laboratory analyses that include hematology, chemistry, and urinalysis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
76
Elvucitabine 10 mg orally daily
Lamivudine 300 mg orally daily
Tenofovir open-label 300 mg orally daily
Efavirenze open-label 600 mg orally daily
Clinical Trial Site
Little Rock, Arkansas, United States
Clinical Trial Site
Long Beach, California, United States
Clinical Trial Site
Los Angeles, California, United States
Clinical Trial Site
Washington D.C., District of Columbia, United States
Clinical Trial Site
Clearwater, Florida, United States
Clinical Trial Site
Fort Myers, Florida, United States
Clinical Trial Site
Miami, Florida, United States
Clinical Trial Site
Miami, Florida, United States
Clinical Trial Site
Orlando, Florida, United States
Clinical Trial Site
Tampa, Florida, United States
...and 16 more locations
The Proportion Of Participants With Virologic Response For 10 mg/Day Elvucitabine In HIV-1-Infected Participants By 12 Weeks Compared With The Proportion Of Participants With Lamivudine 300 mg/Day
The proportion of participants having achieved a virologic response for elvucitabine 10 mg/day in combination with efavirenz and tenofovir in HIV-1-infected participants over 12 weeks compared with the proportion of participants having achieved a virologic response for lamivudine 300 mg/day in combination with efavirenz and tenofovir. Virologic response was defined as having achieved undetectable (\<50 copies/mL) HIV-1 RNA levels from baseline assessment.
Time frame: 12 weeks
The Safety Profile Of Elvucitabine.
Determination of the safety profile of elvucitabine as defined by the frequency, type and severity of treatment-emergent adverse events (AEs) and the frequency of Grade 3 and Grade 4 laboratory abnormalities.
Time frame: 12 weeks
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