Elvucitabine/Efavirenz/Tenofovir Versus Lamivudine/Efavirenz/Tenofovir in Human Immunodeficiency Virus (HIV)-1 Infected, Treatment-naive Participants
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Elvucitabine; Lamivudine; Tenofovir; Efavirenz
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Elvucitabine 10 mg orally daily; Lamivudine 300 mg orally daily; Tenofovir open-label 300 mg orally daily; Efavirenze open-label 600 mg orally daily
Other intervention name(s): ACH-126,443; 3TC; Viread; Sustiva
Intervention MeSH terms: Tenofovir; Lamivudine; Efavirenz; Dexelvucitabine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: HIV-1 treatment naive