Clinical trial NCT01227824: A Trial Comparing GSK1349572 50mg Once Daily to Raltegravir 400mg Twice Daily
Official title: A Randomized, Double Blind Study of the Safety and Efficacy of GSK1349572 50mg Once Daily to Raltegravir 400mg Twice Daily Both Administered With Fixed-dose Dual Nucleoside Reverse Transcriptase Inhibitor Therapy Over 96 Weeks in HIV-1 Infected Antiretroviral Therapy Naive Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infection, Human Immunodeficiency Virus I
Keywords: integrase inhibitor
HIV Infection
raltegravir
GSK1349572
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
Collaborators: name: Shionogi
name: GlaxoSmithKline
First posted: 2010-10-25
Enrollment: 828
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: ING113086 is a Phase 3 randomized, double-blind, double dummy, active-controlled, multicenter, study conducted in approximately 788 HIV-1 infected ART-naïve subjects. Subjects will be randomized 1:1 one of the following treatment arms:

1. GSK1349572 50 mg once daily (approximately 394 subjects) + fixed-dose dual NRTI therapy (either ABC/3TC or TDF/FTC)

   OR
2. 400 mg RAL twice daily (approximately 394 subjects) + fixed-dose dual NRTI therapy (either ABC/3TC or TDF/FTC)

Analyses will be conducted at 48 weeks and 96 weeks. Subjects randomized to receive GSK1349572 and who successfully complete 96 weeks of treatment will continue to have access to GSK1349572 through the study until either it is locally available, as long as they continue to derive clinical benefit.

ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of Participants With Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) [HIV-1RNA] <50 Copies (c)/Milliliter (mL) Through Week 48
timeFrame: Baseline up to Week 48
Secondary outcomes:
measure: Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance.
timeFrame: Week 48 and Week 96
measure: Number of Participants With Plasma HIV-1 RNA <50 c/mL
timeFrame: Week 96
measure: Number of Participants With Plasma HIV-1 RNA <400 c/mL
timeFrame: Week 48 and Week 96
measure: Change From Baseline in Plasma HIV-1 RNA Over Time
timeFrame: Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
measure: Absolute Values in Plasma HIV-1 RNA Over Time
timeFrame: Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
measure: Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time
timeFrame: Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
measure: Absolute Values in CD4+ Cell Counts Over Time
timeFrame: Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
measure: Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences
timeFrame: From Baseline until Week 96
measure: Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs)
timeFrame: From Baseline until Week 96
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Time Tau [AUC(0-tau)] of DTG
timeFrame: Week 4, Week 24, and Week 48
measure: Maximum Plasma Concentration (Cmax) and Concentration at the End of a Dosing Interval (Ctau) of DTG
timeFrame: Week 4, Week 24, and Week 48
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Torrance
country: United States
facility: GSK Investigational Site
state: California
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: GSK Investigational Site
state: Florida
city: Fort Pierce
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Hillsborough
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Columbia
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Darlinghurst
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Surry Hills
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Melbourne
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Hamilton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Garches
country: France
facility: GSK Investigational Site
city: Le Kremlin Bicêtre cedex
country: France
facility: GSK Investigational Site
city: Levallois Perret
country: France
facility: GSK Investigational Site
city: Lyon Cedex 03
country: France
facility: GSK Investigational Site
city: Marseille
country: France
facility: GSK Investigational Site
city: Nantes
country: France
facility: GSK Investigational Site
city: Paris Cedex 10
country: France
facility: GSK Investigational Site
city: Paris Cedex 12
country: France
facility: GSK Investigational Site
city: Paris Cedex 13
country: France
facility: GSK Investigational Site
city: Paris Cedex 4
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Fuerth
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Bonn
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Dortmund
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Cona (Ferrara)
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Roma
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Genova
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Brescia
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Torino
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Rovigo
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Krasnodar
country: Russian Federation
facility: GSK Investigational Site
city: Lipetsk
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: N.Novgorod
country: Russian Federation
facility: GSK Investigational Site
city: Orel
country: Russian Federation
facility: GSK Investigational Site
city: Perm
country: Russian Federation
facility: GSK Investigational Site
city: Saratov
country: Russian Federation
facility: GSK Investigational Site
city: Smolensk
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Volgograd
country: Russian Federation
facility: GSK Investigational Site
city: (Móstoles) Madrid
country: Spain
facility: GSK Investigational Site
city: Alcala de Henares
country: Spain
facility: GSK Investigational Site
city: Alicante
country: Spain
facility: GSK Investigational Site
city: Almería
country: Spain
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Cartagena (Murcia)
country: Spain
facility: GSK Investigational Site
city: Córdoba
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: La Coruña
country: Spain
facility: GSK Investigational Site
city: La Laguna (Santa Cruz De Tenerife)
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Malaga
country: Spain
facility: GSK Investigational Site
city: Mataró
country: Spain
facility: GSK Investigational Site
city: Murcia
country: Spain
facility: GSK Investigational Site
city: San Sebastián
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Vigo ( Pontevedra)
country: Spain
facility: GSK Investigational Site
city: Birmingham
country: United Kingdom
facility: GSK Investigational Site
state: Warwickshire
city: Brighton
country: United Kingdom
facility: GSK Investigational Site
city: Crumpsall, Manchester
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.