Overview

This trial is active, not recruiting.

Condition infection, human immunodeficiency virus
Treatment dolutegravir
Phase phase 3
Sponsor ViiV Healthcare
Collaborator Shionogi
Start date May 2011
End date May 2012
Trial size 183 participants
Trial identifier NCT01328041, 112574

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
dolutegravir plus background antiretroviral therapy optimised at Day 8
dolutegravir
50 mg twice daily

Primary Outcomes

Measure
Mean Change From Baseline in Plasma HIV-1 RNA at Day 8
time frame: Baseline and Day 8
Number of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 24
time frame: Week 24
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)
time frame: From the day of the first dose of study drug until study medication discontinuation or Week 48 analysis data cut-off (median of 507 study days)
Number of Participants With Adverse Events of the Indicated Severity, Per the Division of Acquired Immune Deficiency Syndrome (DAIDS) Grading Scale
time frame: From the day of the first dose of study drug until study medication discontinuation or Week 48 analysis data cut-off (median of 507 study days)
Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade
time frame: From the day of the first dose of study drug until study medication discontinuation or Week 48 analysis data cut-off (median of 507 study days)
Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade
time frame: From the day of the first dose of study drug until study medication discontinuation or Week 48 analysis data cut-off (median of 507 study days)

Secondary Outcomes

Measure
Number of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48
time frame: Week 48
Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48
time frame: Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48
Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48
time frame: Baseline; Day 8; Weeks 4, 8, 12, 16, 24, 32, 40, and 48
Absolute Values for CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Weeks 4, 12, 24, and 48
time frame: Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48
Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and in CD8+ Cell Counts at Weeks 4, 12, 24, and 48
time frame: Baseline; Day 8; Weeks 4, 8, 12, 16, 24, 32, 40, and 48
Ratio of CD4+/CD8+ Cell Count at Baseline and Weeks 4, 12, 24, and 48
time frame: Baseline; Weeks 4, 12, 24, and 48
Number of Participants With HIV-1 Disease Progression (Acquired Immune Deficiency Syndrome [AIDS] or Death)
time frame: From Baseline to Week 48
Cmax and Ctau of DTG
time frame: Day 8, Week 4, and Week 24
AUC(0-tau) and AUC(0-24) of DTG
time frame: Day 8, Week 4, and Week 24
C0 Assessment of DTG
time frame: Day 8, Week 4, and Week 24
Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF) as a Measure of Genotypic Resistance
time frame: From the start of study treatment to date cut-off (median of 507 study days)
Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) Between Baseline and the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance
time frame: From the start of study treatment to data cut-off (median of 507 study days)

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title 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.
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2014.
Information provided to ClinicalTrials.gov by ViiV Healthcare.