A Study to Assess Dolutegravir in HIV-infected Subjects With Treatment Failure on an Integrase Inhibitor Containing Regimen.

A Phase III Study to Demonstrate the Antiviral Activity and Safety of Dolutegravir in HIV-1 Infected Adult Subjects With Treatment Failure on an Integrase Inhibitor Containing Regimen.

The purpose of this trial is to assess the antiviral activity and safety of a dolutegravir (DTG) containing regimen in HIV-1 infected, antiretroviral therapy (ART)-experienced adults with current or historical failure on an integrase inhibitor (INI) containing regimen. The study will assess DTG 50mg twice daily administered initially with the current failing ART regimen but then with an optimised background ART regimen (OBR) after Day 7. The first analyses will be conducted after the last subject enrolled has completed 24 weeks. Subjects may remain on study after Week 24.

ING112574 is a Phase 3, multicentre, open-label, single arm study to assess the antiviral activity and safety of DTG containing regimen in HIV-1 infected ART-experienced adults with historical or current evidence of resistance to RAL or ELV. Initially, a minimum of 100 subjects will be enrolled to receive DTG 50mg twice daily with the current failing regimen for 7 days but with OBR from Day 8. Subjects must also have documented genotypic and/or phenotypic resistance to at least one compound in two or more of the other approved classes of ART but must also be able to include at least one fully active drug in the OBR to be started Day 8. The first data cut will take place after the (approximate) 100th subject enrolled completes the Week 24 visit. Enrollment will continue until a further 50 to 100 subjects have been recruited. All subjects who successfully complete 24 weeks of treatment will continue to have access to DTG until it is locally available as long as they continue to derive clinical benefit.

ViiV Healthcare is the sponsor of this study.

Inclusion Criteria:

• Screening plasma HIV-1 RNA ≥500 copies/mL
• ART-experienced, INI-experienced, DTG naïve
• Experienced virological failure on raltegravir (RAL) or elvitegravir (ELV) regimen
• The subject's HIV-1 shows resistance to RAL or ELV at Screening or at prior time point of virological failure on RAL or ELV
• Documented resistance to at least one drug from each of three or more of all approved classes of ART
• 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 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 activity against HIV-1 in vitro within 28 days of first dose of investigational product
• Treatment with etravirine, efavirenz, or nevirapine within 14 days of Day 1(etravirine may be used if coadministered with lopinivir/ritonavir or darunavir/ritonavir)
• Treatment with tipranivir/ritonavir, fosamprenavir, or fosamprenavir/ritonavir within 28 days prior to Screening
• Verified Grade 4 laboratory abnormality 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