Study Assessing Dolutegravir in HIV-1 Infected Subjects With Virus Resistant to Raltegravir and/or Elivitegravir

NCT ID: NCT01568892

Last Updated: 2018-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-18
• Study Completion Date: 2013-12-16

Brief 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.

Detailed 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.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

DTG 50 mg BID

Subjects will receive dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all subjects will continue to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.

Group Type: EXPERIMENTAL

Dolutegravir 50 mg twice daily

Intervention Type: DRUG

Active dolutegravir plus failing background regimen (Day 1 to Day 7). Open label dolutegravir plus optimized background regimen (from Day 8)

Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase

Subjects will receive matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all subjects will continue to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.

Group Type: EXPERIMENTAL

Dolutegravir 50 mg twice daily

Intervention Type: DRUG

Active dolutegravir plus failing background regimen (Day 1 to Day 7). Open label dolutegravir plus optimized background regimen (from Day 8)

Dolutegravir placebo twice daily

Intervention Type: DRUG

Dolutegravir placebo plus failing background regimen (Day 1 to Day 7)

Interventions

Dolutegravir 50 mg twice daily

Active dolutegravir plus failing background regimen (Day 1 to Day 7). Open label dolutegravir plus optimized background regimen (from Day 8)

Intervention Type: DRUG

Dolutegravir placebo twice daily

Dolutegravir placebo plus failing background regimen (Day 1 to Day 7)

Intervention Type: DRUG

Other Intervention Names

GSK1349572; GSK1349572 Placebo

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shionogi

INDUSTRY

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

ViiV Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

GSK Investigational Site

Little Rock, Arkansas, United States

GSK Investigational Site

Bakersfield, California, United States

GSK Investigational Site

Beverly Hills, California, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

San Diego, California, United States

GSK Investigational Site

Norwalk, Connecticut, United States

GSK Investigational Site

Washington D.C., District of Columbia, United States

GSK Investigational Site

Washington D.C., District of Columbia, United States

GSK Investigational Site

Fort Lauderdale, Florida, United States

GSK Investigational Site

Ft. Pierce, Florida, United States

GSK Investigational Site

Orlando, Florida, United States

GSK Investigational Site

Augusta, Georgia, United States

GSK Investigational Site

Savannah, Georgia, United States

GSK Investigational Site

Maywood, Illinois, United States

GSK Investigational Site

Boston, Massachusetts, United States

GSK Investigational Site

Hillsborough, New Jersey, United States

GSK Investigational Site

Buffalo, New York, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

The Bronx, New York, United States

GSK Investigational Site

Valhalla, New York, United States

GSK Investigational Site

Durham, North Carolina, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Austin, Texas, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Annandale, Virginia, United States

Countries

United States

References

Akil B, Blick G, Hagins DP, Ramgopal MN, Richmond GJ, Samuel RM, Givens N, Vavro C, Song IH, Wynne B, Ait-Khaled M; VIKING-4 study team. Dolutegravir versus placebo in subjects harbouring HIV-1 with integrase inhibitor resistance associated substitutions: 48-week results from VIKING-4, a randomized study. Antivir Ther. 2015;20(3):343-8. doi: 10.3851/IMP2878. Epub 2014 Oct 16.

Reference Type: DERIVED

PMID: 25321146 (View on PubMed)

Other Identifiers

116529

Identifier Type: -

Identifier Source: org_study_id