Overview

This trial is active, not recruiting.

Condition infection, human immunodeficiency virus
Treatments dolutegravir 50 mg twice daily, dolutegravir placebo twice daily, open-label dolutegravir 50mg twice daily
Phase phase 3
Sponsor ViiV Healthcare
Collaborator Shionogi
Start date April 2012
End date October 2012
Trial size 30 participants
Trial identifier NCT01568892, 116529

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Active dolutegravir plus failing background regimen (Day 1 to Day 7)
dolutegravir 50 mg twice daily GSK1349572
Active dolutegravir plus failing background regimen (Day 1 to Day 7)
(Experimental)
Dolutegravir placebo plus failing background regimen (Day 1 to Day 7)
dolutegravir placebo twice daily GSK1349572 Placebo
Dolutegravir placebo plus failing background regimen (Day 1 to Day 7)
(Experimental)
Open label dolutegravir plus optimized background regimen (From Day 8)
open-label dolutegravir 50mg twice daily GSK1349572
Open label dolutegravir plus optimized background regimen (from Day 8)

Primary Outcomes

Measure
Mean Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at Day 8
time frame: Baseline and Day 8

Secondary Outcomes

Measure
Absolute Values in Plasma HIV-1 RNA Over Time
time frame: Baseline, Day 8, Day 28, and Week 8
Mean Change From Baseline in Plasma HIV-1 RNA Over Time
time frame: Baseline, Day 8, Day 28, and Week 8
Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time
time frame: Baseline, Day 8, Day 28, and Week 8
Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time
time frame: Baseline, Day 8, Day 28, and Week 8
Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time
time frame: Baseline, Day 8, Day 28, and Week 8
Median Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time
time frame: Baseline, Day 8, Day 28, and Week 8
Absolute Values in Cluster of Differentiation 8+ (CD8+) Cell Counts at Baseline and Day 28
time frame: Baseline and Day 28
Median Change From Baseline in Cluster of Differentiation 8+ (CD8+) Cell Counts at Day 28
time frame: Baseline and Day 28
Number of Participants With the Indicated Type of HIV-1 Disease Progression (Acquired Immunodeficiency Syndrome [AIDS] or Death [DT])
time frame: From the day of the first dose of study drug until early withdrawal or the Day 8 analysis cut-off date (average of 14 study weeks)
Number of Participants With Any Adverse Event (Serious and Non-serious) of the Indicated Grade
time frame: From the first dose of study medication until early withdrawal or through the Day 8 analysis data cut-off date (average of 14 study weeks)
Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade
time frame: From the first dose of study medication until early withdrawal or through the Day 8 analysis data cut-off date (average of 14 study weeks)
Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade
time frame: From the first dose of study medication until early withdrawal or through the Day 8 analysis data cut-off date (average of 14 study weeks)
AUC(0-tau) of DTG
time frame: Day 8, Day 28, and Week 24
Cmax of DTG
time frame: Day 8, Day 28, and Week 24
Plasma DTG Pre-dose Concentration (C0) at Day 8, Day 28, and Week 24; and Average DTG C0 (C0 Avg) at Week 24
time frame: Day 8, Day 28, and Week 24
Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance
time frame: From the first dose of study medication until early withdrawal or through the Day 8 analysis data cut-off date (average of 96 study days)
Number of Participants With the Indicated Fold Increase in Fold Change (FC) in the 50% Inhibitory Concentration Relative to Wild-type Virus for DTG (i.e. PDVF FC/Baseline FC Ratio) at the Time of PDVF, as a Measure of Phenotypic Resistance
time frame: From the first dose of study medication until early withdrawal or through the Day 8 analysis data cut-off date (average of 96 study days)

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Phase III Randomized, Double-blind Trial Investigating the Activity of Dolutegravir 50 mg BID vs Placebo Over 7 Days in HIV-1-infected Subjects With RAL/ELV Resistance, Followed by an Open-label Phase With an Optimized Background Regimen
Description Study ING116529 is a multicenter, randomized, study with an initial 7 day placebo-controlled, functional monotherapy phase to assess the antiviral activity and safety of a dolutegravir (DTG, GSK1349572) containing regimen in HIV-1 infected, ART-experienced adults with virological failure on an integrase inhibitor (INI) containing regimen. Subjects must have evidence of genotypic resistance to raltegravir [RAL] or elvitegravir [ELV] at Screening and documented current or historical genotypic or phenotypic resistance to at least two other antiretroviral therapy drug classes. The study is designed to provide an accurate measure of the intrinsic antiviral activity of DTG 50mg twice daily versus placebo both administered with the current failing regimen in a randomised double-blind phase to Day 8. This will be followed by an open label phase with all subjects receiving DTG 50mg twice daily with an optimized background regimen (containing at least one fully active drug) until subjects no longer derive clinical benefit or until DTG is locally available. 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 at Day 1). 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 The primary analysis will be conducted after the last subject enrolled has completed the randomised, double-blind phase at Day 8. Additional analyses may be performed prior to study closure when all ongoing subjects transition to locally available commercial DTG.
Trial information was received from ClinicalTrials.gov and was last updated in January 2014.
Information provided to ClinicalTrials.gov by ViiV Healthcare.