Study Assessing Dolutegravir in HIV-1 Infected Subjects With Virus Resistant to Raltegravir and/or Elivitegravir
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Dolutegravir 50 mg twice daily; Dolutegravir placebo twice daily
Intervention description: Active dolutegravir plus failing background regimen (Day 1 to Day 7). Open label dolutegravir plus optimized background regimen (from Day 8); Dolutegravir placebo plus failing background regimen (Day 1 to Day 7)
Intervention MeSH terms: Dolutegravir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ART-experienced; GSK1349572; Integrase inhibitor resistance; Dolutegravir

Summary:

      Study ING116529 is a multicenter, randomized, study with an initial 7 day placebo-
      controlled, functional monotherapy phase to quantify the antiviral activity attributable to
      dolutegravir (DTG) in HIV-1 infected, ART-experienced adults who are experiencing virological
      failure on an Integrase inhibitor containing regimen (current RAL or ELV failures), with
      evidence of genotypic resistance to RAL or ELV at study entry. Thirty subjects will be
      randomized (1:1) to receive either DTG 50mg BID (Arm A) or Placebo (Arm B) with the current
      failing regimen for 7 days (RAL or ELV should be discontinued prior to dosing with DTG). At
      Day 8, subjects from both arms will enter an open label phase and receive open label DTG 50mg
      BID with an optimized background regimen containing at least one fully active drug.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Screening plasma HIV-1 RNA ≥1000 copies/mL

          -  ART-experienced, INI-experienced, DTG naïve

          -  Current virological failure on raltegravir (RAL) or elvitegravir (ELV) regimen

          -  The subject's HIV-1 shows genotypic resistance to RAL or ELV at Screening

          -  Subject has been on stable ART for at least one month prior to Screening and through
             Day 1(with exceptions for ETV, EFV and NVP that can be interrupted within 14 days of
             Day 1, see Exclusion Criterion)

          -  Documented resistance to at least one drug from each of two or more of any approved
             classes of ART other than integrase inhibitors

          -  Be able to receive at least one fully active drug as part of the OBR from Day 8

          -  Women capable of becoming pregnant must use appropriate contraception during the study
             (as defined by the protocol)

          -  Willing and able to understand and provide signed and dated written informed consent
             prior to Screening.

        Exclusion Criteria:

          -  Women who are pregnant or breast feeding

          -  An active AIDS-defining condition at Screening (except cutaneous Kaposi's sarcoma not
             requiring systemic therapy or CD4+ <200c/mm3)

          -  Moderate to severe hepatic impairment as defined by Child-Pugh classification

          -  Anticipated need for HCV therapy during the first 24 weeks of the study

          -  Recent history (less than or equal to 3 months) of any upper or lower gastrointestinal
             bleed, with the exception of anal or rectal bleeding

          -  Allergy or intolerance to the study drugs or their components or drugs of their class

          -  Malignancy within the past 6 months

          -  Treatment with an HIV-1 therapeutic vaccine within 90 days of Screening

          -  Treatment with radiation therapy, cytotoxic chemotherapeutic agents or any
             immunomodulator within 28 days of Screening

          -  Treatment with any agent, other than licensed ART, with documented in vitro/vivo
             activity against HIV-1 within 28 days of first dose of investigational product (with
             the exception of entecavir if required for Hep B treatment)

          -  Treatment with etravirine, efavirenz, or nevirapine within 14 days of Day 1(etravirine
             may be used if coadministered with lopinavir/ritonavir or darunavir/ritonavir)

          -  Treatment with tipranivir/ritonavir, fosamprenavir, or fosamprenavir/ritonavir within
             28 days prior to Screening

          -  Exposure to an experimental drug or vaccine within either 28 days, 5 half-lives of the
             test agent, or twice the duration of the biological effect of the test agent, which
             ever is longer, prior to the first dose of IP.

          -  Any acute or verified Grade 4 laboratory abnormality (with the exception of Grade 4
             lipids) at Screening

          -  ALT> 5 times the upper limit of normal (ULN) at Screening

          -  ALT ≥ 3X ULN and bilirubin > 1.5 X ULN (with 35% direct bilirubin) at Screening