Dose Ranging Study of GSK1265744 Plus Nucleoside Reverse Transcriptase Inhibitors for Induction of Human Immunodeficiency Virus-1 (HIV-1) Virologic Suppression Followed by Virologic Suppression Maintenance by GSK1265744 Plus Rilpivirine
Condition: Infection, Human Immunodeficiency Virus; HIV Infections
MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes
Intervention: GSK1265744 10 mg; GSK1265744 30 mg; GSK1265744 60 mg; Efavirenz 600 mg; Rilpivirine 25 mg; Placebo; Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC)
Intervention description: GSK1265744 10 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.; GSK1265744 30 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.; GSK1265744 60 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.; Efavirenz 600 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase and Maintenance Phase of the study.; Rilpivirine 25 mg will be administered orally once daily in combination with GSK1265744 10 mg, 30 mg and 60 mg in the Maintenance Phase of the study.; Placebo matching to GSK1265744 will be administered along with GSK1265744 10 mg and 30 mg in the Induction phase and Maintenance phase of the study.; The background dual NRTI therapy for all arms in the Induction Phase and Efavirenz 600 mg arm in the Maintenance Phase will be either abacavir 600 mg + lamivudine 300 mg (ABC/3TC) or tenofovir 300 mg + emtricitabine 200 mg (TDF/FTC) as selected by the Investigator.
Intervention MeSH terms: Tenofovir; Lamivudine; Emtricitabine; Efavirenz; Abacavir; Rilpivirine; Cabotegravir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 244.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV -1; GSK1265744; maintenance phase; dose selection

Summary:

      The study is designed to select a dose of GSK1265744 primarily on the basis of antiviral
      activity and tolerability in HIV-1 infected, antiretroviral naive subjects.

      This study consists of two parts:

      Induction Phase: Approximately 200 subjects will be randomized (50 subjects in each of the 4
      treatment arms). The Induction Phase consists of a 24 week dose-ranging evaluation of
      GSK1265744 at blinded doses of 10 mg, 30 mg and 60 mg once-daily and a control arm of
      open-label efavirenz (EFV) 600 mg once daily. The background dual nucleoside reverse
      transcriptase inhibitor (NRTI) antiretroviral therapy (ART) for all arms will be either
      abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) as selected by the
      Investigator. Subjects randomized to a GSK1265744 containing arm, who successfully complete
      24 weeks on study and demonstrate virologic suppression (defined as having a plasma HIV-1
      ribonucleic acid [RNA] <50 copies per milliliter [c/mL] before Week 24, with no signs of
      virologic rebound) will become eligible for the Maintenance Phase of this study.

      Maintenance Phase: The background NRTIs will be discontinued and the subjects will continue
      their randomized dose of GSK1265744 in combination with rilpivirine (RPV) 25 mg once-daily
      for an additional 72 weeks. The Maintenance phase will evaluate the ability of this two drug
      ART regimen to maintain virologic suppression through Week 48, Week 72 and Week 96. Subjects
      randomized to the EFV arm will continue on their randomized regimen through Week 96.

      After completion of the maintenance phase, subjects could enroll in the Open-Label Phase to
      continue GSK1265744 + RPV treatment as long as they continue to derive clinical benefit and
      until it is locally approved and commercially available.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infected male or female subjects >= 18 years of age

          -  Screening plasma HIV-1 RNA >=1000 c/mL

          -  CD4+ cell count >=200 cells/millimeter (mm)^3

          -  ART-naive defined as having =<10 days of prior therapy with any antiretroviral agent
             following a diagnosis of HIV-1 infection

          -  Female subjects of child bearing potential are eligible to enter if they are not
             pregnant and willing to use protocol-specified methods of contraception to prevent
             pregnancy during the study

        Exclusion Criteria:

          -  Any evidence at screening of an active Centers for Disease and Prevention Control
             (CDC) Category C disease

          -  Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening

          -  History of ongoing or clinically relevant hepatitis within the previous 6 months, and
             subjects with moderate to severe hepatic impairment will be excluded

          -  Women who are breastfeeding

          -  Subject, who in the investigator's judgment, poses a significant suicide risk

          -  Any clinically significant finding on screening or baseline electrocardiograph (ECG)

          -  The presence of any specific laboratory abnormalities at Screening

          -  History of cardiac disease

          -  Clinically relevant pancreatitis

          -  Subjects who are unlikely to complete the dosing schedule due to a pre-existing
             physical or mental condition

          -  Any condition which impairs the absorption, distribution, metabolism or excretion of
             the investigational product

          -  Any evidence of primary resistance based upon the presence of a major resistance
             associated mutation in the Screening HIV genotype, or any historical genotype

          -  Treatment with any protocol-specified excluded medication