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

NCT01568892 | Completed Phase 3 Results

• 1 other identifier: 116529
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 25

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.

Conditions

HIV Infections

Keywords

ART-experienced; GSK1349572; Integrase inhibitor resistance; Dolutegravir

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at Day 8

  Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1) and Day 8. Change from Baseline was calculated as the value at Day 8 minus the value at Baseline (Day 1). The analysis was performed using statistical modeling correcting for Baseline plasma HIV-1 RNA, Baseline Dolutegravir (DTG) fold change (FC), the overall susceptibility score (OSS) of the failing regimen, and the interaction between DTG FC and treatment. Means and differences were calculated using the average Baseline DTG FC of the entire Intent-to-Treat Exposed (ITT-E) Population. The last observation carried forward with discontinuation equals Baseline (LOCFDB) dataset was used for the analysis. For the LOCFDB dataset, missing values were carried forward from the previous, non-missing, available on-treatment assessment, except formissing values due to premature withdrawal or Day 8 missing values, which had the Baseline value imputed.

  Baseline and Day 8

Secondary Outcomes (32)

• Absolute Values in Plasma HIV-1 RNA Over Time

  Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84

• Mean Change From Baseline in Plasma HIV-1 RNA Over Time

  Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84

• Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time

  Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40 and 48

• Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time

  Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40 and 48

• Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time

  Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84

Study Arms (2)

DTG 50 mg BID

EXPERIMENTAL

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.

Drug: Dolutegravir 50 mg twice daily

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

EXPERIMENTAL

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.

Drug: Dolutegravir 50 mg twice daily; Drug: Dolutegravir placebo twice daily

Interventions

Dolutegravir 50 mg twice daily DRUG

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

Also known as: GSK1349572

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

Dolutegravir placebo twice daily DRUG

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

Also known as: GSK1349572 Placebo

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• ViiV Healthcare: lead
• Shionogi: collaborator
• GlaxoSmithKline: collaborator

Study Sites (25)

GSK Investigational Site

Little Rock, Arkansas, 72207, United States

Location

GSK Investigational Site

Bakersfield, California, 93301, United States

Location

GSK Investigational Site

Beverly Hills, California, 90211, United States

Location

GSK Investigational Site

Los Angeles, California, 90069, United States

Location

GSK Investigational Site

San Diego, California, 92103-8208, United States

Location

GSK Investigational Site

Norwalk, Connecticut, 06850, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20009, United States

Location

GSK Investigational Site

Fort Lauderdale, Florida, 33316, United States

Location

GSK Investigational Site

Ft. Pierce, Florida, 34982, United States

Location

GSK Investigational Site

Orlando, Florida, 32803, United States

Location

GSK Investigational Site

Augusta, Georgia, 30912, United States

Location

GSK Investigational Site

Savannah, Georgia, 31401, United States

Location

GSK Investigational Site

Maywood, Illinois, 60153, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02115, United States

Location

GSK Investigational Site

Hillsborough, New Jersey, 08844, United States

Location

GSK Investigational Site

Buffalo, New York, 14215, United States

Location

GSK Investigational Site

New York, New York, 10011, United States

Location

GSK Investigational Site

The Bronx, New York, 10467, United States

Location

GSK Investigational Site

Valhalla, New York, 10595, United States

Location

GSK Investigational Site

Durham, North Carolina, 27710, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19140, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

Annandale, Virginia, 22003, United States

Location

Related Publications (1)

• 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.

  PMID: 25321146 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

dolutegravir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2012
• First Posted: April 2, 2012
• Study Start: April 18, 2012
• Primary Completion: October 31, 2012
• Study Completion: December 16, 2013
• Last Updated: July 2, 2018
• Results First Posted: February 19, 2014

Record last verified: 2018-06

Locations

US (25)