A Trial Comparing GSK1349572 50mg Once Daily to Raltegravir 400mg Twice Daily

NCT01227824 | Completed Phase 3 Results

• 1 other identifier: 113086
• Study Type: interventional
• Target: 828
• Locations: 9 countries
• Sites: 101

Brief Summary

The purpose of this trial is to assess the non-inferior antiviral activity of GSK1349572 50 mg once daily versus RAL 400mg twice daily over 48 weeks; non-inferiority will also be tested at Week 96. Both GSK1349572 and RAL will be given in combination with fixed-dose dual NRTI therapy (ABC/3TC or TDF/FTC). This study will be conducted in HIV-1 infected ART-naïve adult subjects.

Conditions

Infection, Human Immunodeficiency Virus I

Keywords

integrase inhibitor; HIV Infection; raltegravir; GSK1349572

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) [HIV-1RNA] <50 Copies (c)/Milliliter (mL) Through Week 48

  Percentage of participants with plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) with \<50 c/mL was assessed using the Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) snapshot algorithm. The algorithm treats all participants without HIV-1 RNA data as non-responders, as well as participants who switch their concomitant Antiretroviral Therapy (ART) prior to Week 48 as follows: background ART substitutions not permitted per study; background ART substitutions permitted per study unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure will be determined by the last available HIV-1 RNA assessment while the subject was on-treatment. Intent-to-Treat Exposed (ITT-E) Population comprised all randomized participants who received at least one dose of study medication.

  Baseline up to Week 48

Secondary Outcomes (11)

• Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance.

  Week 48 and Week 96

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

  Week 96

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

  Week 48 and Week 96

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

  Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96

• Absolute Values in Plasma HIV-1 RNA Over Time

  Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96

Study Arms (2)

GSK1349572 (N=~394)

EXPERIMENTAL

GSK1349572 50mg once daily + raltegravir placebo twice daily + NRTI background therapy once daily

Drug: GSK1349572 (dolutegravir); Other: GSK1349572 Placebo; Other: ABC/3TC; Other: TDF/FTC

raltegravir (N=~394)

ACTIVE COMPARATOR

raltegravir 400mg twice daily + GSK1349572 placebo once daily + NRTI background therapy once daily

Drug: raltegravir; Other: ABC/3TC; Other: TDF/FTC; Other: raltegravir Placebo

Interventions

GSK1349572 (dolutegravir) DRUG

GSK1349572 50 mg taken once daily with or without food

GSK1349572 (N=~394)

raltegravir DRUG

raltegravir 400mg taken twice daily

raltegravir (N=~394)

GSK1349572 Placebo OTHER

GSK1349572 placebo taken once daily

GSK1349572 (N=~394)

ABC/3TC OTHER

Abacavir/Lamivudine background therapy once daily

GSK1349572 (N=~394); raltegravir (N=~394)

TDF/FTC OTHER

Tenofovir/emtricitabine background therapy once daily

GSK1349572 (N=~394); raltegravir (N=~394)

raltegravir Placebo OTHER

raltegravir placebo taken twice daily

raltegravir (N=~394)

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 c/mL
• Antiretroviral-naïve (≤ 10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection)
• Ability to understand and sign a written informed consent form
• Willingness to use approved methods of contraception to avoid pregnancy (women of child bearing potential only)
• Age equal to or greater than 18 years

You may not qualify if:

• Women who are pregnant or breastfeeding;
• Active Center for Disease and Prevention Control (CDC) Category C disease
• Moderate to severe hepatic impairment
• Anticipated need for HCV therapy during the study
• Allergy or intolerance to the study drugs or their components or drugs of their class
• Malignancy within the past 5 years
• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening
• Treatment with radiation therapy, cytotoxic chemotherapeutic agents or any immunomodulator within 28 days of Screening
• Exposure to an agent with documented activity against HIV-1 in vitro or an experimental vaccine or drug within 28 days of first dose of study medication
• Primary viral resistance in the Screening result
• Verified Grade 4 laboratory abnormality
• ALT \>5 xULN
• ALT ≥ 3xULN and bilirubin ≥ 1.5xULN (with \>35% direct bilirubin);
• Estimated creatinine clearance \<50 mL/min
• Recent history (≤3 months) of upper or lower gastrointestinal bleed

Sponsors & Collaborators

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

Study Sites (101)

GSK Investigational Site

Phoenix, Arizona, 85012, United States

Location

GSK Investigational Site

Little Rock, Arkansas, 72207, United States

Location

GSK Investigational Site

Long Beach, California, 90813, United States

Location

GSK Investigational Site

Los Angeles, California, 90048, United States

Location

GSK Investigational Site

Los Angeles, California, 90069, United States

Location

GSK Investigational Site

Torrance, California, 90502, United States

Location

GSK Investigational Site

Denver, Colorado, 80209, 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

Atlanta, Georgia, 30339, United States

Location

GSK Investigational Site

St Louis, Missouri, 63108, United States

Location

GSK Investigational Site

Hillsborough, New Jersey, 08844, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28209, United States

Location

GSK Investigational Site

Columbia, South Carolina, 29203, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

Houston, Texas, 77004, United States

Location

GSK Investigational Site

Houston, Texas, 77098, United States

Location

GSK Investigational Site

Seattle, Washington, 98104, United States

Location

GSK Investigational Site

Darlinghurst, New South Wales, 2010, Australia

Location

GSK Investigational Site

Surry Hills, New South Wales, 2010, Australia

Location

GSK Investigational Site

Melbourne, Victoria, 3004, Australia

Location

GSK Investigational Site

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

GSK Investigational Site

Hamilton, Ontario, L8N 3Z5, Canada

Location

GSK Investigational Site

Ottawa, Ontario, K1H 8L6, Canada

Location

GSK Investigational Site

Toronto, Ontario, M4N 3M5, Canada

Location

GSK Investigational Site

Toronto, Ontario, M4T 3A7, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2L 5B1, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2X 2P4, Canada

Location

GSK Investigational Site

Garches, 92380, France

Location

GSK Investigational Site

Le Kremlin-Bicêtre, 94275, France

Location

GSK Investigational Site

Levallois-Perret, 92300, France

Location

GSK Investigational Site

Lyon, 69437, France

Location

GSK Investigational Site

Marseille, 13003, France

Location

GSK Investigational Site

Nantes, 44093, France

Location

GSK Investigational Site

Paris, 75018, France

Location

GSK Investigational Site

Paris, 75181, France

Location

GSK Investigational Site

Paris, 75475, France

Location

GSK Investigational Site

Paris, 75571, France

Location

GSK Investigational Site

Paris, 75651, France

Location

GSK Investigational Site

Fürth, Bavaria, 90762, Germany

Location

GSK Investigational Site

Munich, Bavaria, 80335, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Bonn, North Rhine-Westphalia, 53127, Germany

Location

GSK Investigational Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

GSK Investigational Site

Dortmund, North Rhine-Westphalia, 44137, Germany

Location

GSK Investigational Site

Berlin, 13353, Germany

Location

GSK Investigational Site

Hamburg, 20146, Germany

Location

GSK Investigational Site

Hamburg, 20246, Germany

Location

GSK Investigational Site

Cona (Ferrara), Emilia-Romagna, 44124, Italy

Location

GSK Investigational Site

Rome, Lazio, 00168, Italy

Location

GSK Investigational Site

Genoa, Liguria, 16128, Italy

Location

GSK Investigational Site

Brescia, Lombardy, 25123, Italy

Location

GSK Investigational Site

Turin, Piedmont, 10149, Italy

Location

GSK Investigational Site

Rovigo, Veneto, 45100, Italy

Location

GSK Investigational Site

Krasnodar, 350015, Russia

Location

GSK Investigational Site

Lipetsk, 398043, Russia

Location

GSK Investigational Site

Moscow, 105275, Russia

Location

GSK Investigational Site

N.Novgorod, 603005, Russia

Location

GSK Investigational Site

Oryol, 302040, Russia

Location

GSK Investigational Site

Perm, 614088, Russia

Location

GSK Investigational Site

Saint Petersburg, 190103, Russia

Location

GSK Investigational Site

Saint Petersburg, 196645, Russia

Location

GSK Investigational Site

Saratov, 410009, Russia

Location

GSK Investigational Site

Smolensk, 214006, Russia

Location

GSK Investigational Site

Volgograd, 400040, Russia

Location

GSK Investigational Site

(Móstoles) Madrid, 28935, Spain

Location

GSK Investigational Site

A Coruña, 15006, Spain

Location

GSK Investigational Site

Alcalá de Henares, 28805, Spain

Location

GSK Investigational Site

Alicante, 03010, Spain

Location

GSK Investigational Site

Almería, 04009, Spain

Location

GSK Investigational Site

Badalona, 08916, Spain

Location

GSK Investigational Site

Barcelona, 08003, Spain

Location

GSK Investigational Site

Barcelona, 08025, Spain

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Barcelona, 08907, Spain

Location

GSK Investigational Site

Cartagena (Murcia), 30202, Spain

Location

GSK Investigational Site

Córdoba, 14004, Spain

Location

GSK Investigational Site

Granada, 18014, Spain

Location

GSK Investigational Site

Granada, Spain

Location

GSK Investigational Site

La Laguna (Santa Cruz de Tenerife), 38320, Spain

Location

GSK Investigational Site

Madrid, 28006, Spain

Location

GSK Investigational Site

Madrid, 28029, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Mataró, 08304, Spain

Location

GSK Investigational Site

Málaga, 29010, Spain

Location

GSK Investigational Site

Murcia, Spain

Location

GSK Investigational Site

San Sebastián, 20014, Spain

Location

GSK Investigational Site

Seville, 41071, Spain

Location

GSK Investigational Site

Valencia, 46010, Spain

Location

GSK Investigational Site

Vigo ( Pontevedra), 36204, Spain

Location

GSK Investigational Site

Birmingham, Warwickshire, B29 6JD, United Kingdom

Location

GSK Investigational Site

Brighton, BN2 1ES, United Kingdom

Location

GSK Investigational Site

Crumpsall, Manchester, M8 5RB, United Kingdom

Location

GSK Investigational Site

London, E1 1BB, United Kingdom

Location

GSK Investigational Site

London, SW10 9TH, United Kingdom

Location

Related Publications (3)

• Brinson C, Walmsley S, Arasteh K, et al. Dolutegravir treatment response and safety by key subgroups in treatment naive HIV-infected individuals. Published at: Conference on Retroviruses and Opportunistic Infections - 20th Annual; March 3-6, 2013; Atlanta, GA.

  BACKGROUND

• Raffi F, Rachlis A, Stellbrink HJ, Hardy WD, Torti C, Orkin C, Bloch M, Podzamczer D, Pokrovsky V, Pulido F, Almond S, Margolis D, Brennan C, Min S; SPRING-2 Study Group. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet. 2013 Mar 2;381(9868):735-43. doi: 10.1016/S0140-6736(12)61853-4. Epub 2013 Jan 8.

  PMID: 23306000 BACKGROUND

• Raffi F, Jaeger H, Quiros-Roldan E, Albrecht H, Belonosova E, Gatell JM, Baril JG, Domingo P, Brennan C, Almond S, Min S; extended SPRING-2 Study Group. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet Infect Dis. 2013 Nov;13(11):927-35. doi: 10.1016/S1473-3099(13)70257-3. Epub 2013 Sep 25.

  PMID: 24074642 DERIVED

MeSH Terms

Conditions

Infections; HIV Infections

Interventions

dolutegravir; Raltegravir Potassium

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; 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

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2010
• First Posted: October 25, 2010
• Study Start: October 19, 2010
• Primary Completion: February 6, 2012
• Study Completion: December 27, 2016
• Last Updated: October 9, 2018
• Results First Posted: June 23, 2014

Record last verified: 2018-10

Locations

GB (5); DE (10); FR (11); IT (6); CA (7); US (20); AU (3); RU (11); ES (28)