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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01227824




Registration number
NCT01227824
Ethics application status
Date submitted
14/10/2010
Date registered
25/10/2010
Date last updated
9/10/2018

Titles & IDs
Public title
A Trial Comparing GSK1349572 50mg Once Daily to Raltegravir 400mg Twice Daily
Scientific 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
Secondary ID [1] 0 0
113086
Universal Trial Number (UTN)
Trial acronym
SPRING-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infection, Human Immunodeficiency Virus I 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK1349572 (dolutegravir)
Treatment: Drugs - raltegravir
Other interventions - GSK1349572 Placebo
Other interventions - ABC/3TC
Other interventions - TDF/FTC
Other interventions - raltegravir Placebo

Experimental: GSK1349572 (N=~394) - GSK1349572 50mg once daily + raltegravir placebo twice daily + NRTI background therapy once daily

Active comparator: raltegravir (N=~394) - raltegravir 400mg twice daily + GSK1349572 placebo once daily + NRTI background therapy once daily


Treatment: Drugs: GSK1349572 (dolutegravir)
GSK1349572 50 mg taken once daily with or without food

Treatment: Drugs: raltegravir
raltegravir 400mg taken twice daily

Other interventions: GSK1349572 Placebo
GSK1349572 placebo taken once daily

Other interventions: ABC/3TC
Abacavir/Lamivudine background therapy once daily

Other interventions: TDF/FTC
Tenofovir/emtricitabine background therapy once daily

Other interventions: raltegravir Placebo
raltegravir placebo taken twice daily
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) [HIV-1RNA] <50 Copies (c)/Milliliter (mL) Through Week 48
Timepoint [1] 0 0
Baseline up to Week 48
Secondary outcome [1] 0 0
Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance.
Timepoint [1] 0 0
Week 48 and Week 96
Secondary outcome [2] 0 0
Number of Participants With Plasma HIV-1 RNA <50 c/mL
Timepoint [2] 0 0
Week 96
Secondary outcome [3] 0 0
Number of Participants With Plasma HIV-1 RNA <400 c/mL
Timepoint [3] 0 0
Week 48 and Week 96
Secondary outcome [4] 0 0
Change From Baseline in Plasma HIV-1 RNA Over Time
Timepoint [4] 0 0
Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
Secondary outcome [5] 0 0
Absolute Values in Plasma HIV-1 RNA Over Time
Timepoint [5] 0 0
Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
Secondary outcome [6] 0 0
Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time
Timepoint [6] 0 0
Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
Secondary outcome [7] 0 0
Absolute Values in CD4+ Cell Counts Over Time
Timepoint [7] 0 0
Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
Secondary outcome [8] 0 0
Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences
Timepoint [8] 0 0
From Baseline until Week 96
Secondary outcome [9] 0 0
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs)
Timepoint [9] 0 0
From Baseline until Week 96
Secondary outcome [10] 0 0
Area Under the Plasma Concentration-time Curve From Time Zero to Time Tau [AUC(0-tau)] of DTG
Timepoint [10] 0 0
Week 4, Week 24, and Week 48
Secondary outcome [11] 0 0
Maximum Plasma Concentration (Cmax) and Concentration at the End of a Dosing Interval (Ctau) of DTG
Timepoint [11] 0 0
Week 4, Week 24, and Week 48

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/10/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/12/2016
Sample size
Target
Accrual to date
Final
828
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Darlinghurst
Recruitment hospital [2] 0 0
GSK Investigational Site - Surry Hills
Recruitment hospital [3] 0 0
GSK Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2010 - Surry Hills
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
South Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Canada
State/province [14] 0 0
British Columbia
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
France
State/province [17] 0 0
Garches
Country [18] 0 0
France
State/province [18] 0 0
Le Kremlin Bicêtre cedex
Country [19] 0 0
France
State/province [19] 0 0
Levallois Perret
Country [20] 0 0
France
State/province [20] 0 0
Lyon Cedex 03
Country [21] 0 0
France
State/province [21] 0 0
Marseille
Country [22] 0 0
France
State/province [22] 0 0
Nantes
Country [23] 0 0
France
State/province [23] 0 0
Paris Cedex 10
Country [24] 0 0
France
State/province [24] 0 0
Paris Cedex 12
Country [25] 0 0
France
State/province [25] 0 0
Paris Cedex 13
Country [26] 0 0
France
State/province [26] 0 0
Paris Cedex 4
Country [27] 0 0
France
State/province [27] 0 0
Paris
Country [28] 0 0
Germany
State/province [28] 0 0
Bayern
Country [29] 0 0
Germany
State/province [29] 0 0
Hessen
Country [30] 0 0
Germany
State/province [30] 0 0
Niedersachsen
Country [31] 0 0
Germany
State/province [31] 0 0
Nordrhein-Westfalen
Country [32] 0 0
Germany
State/province [32] 0 0
Berlin
Country [33] 0 0
Germany
State/province [33] 0 0
Hamburg
Country [34] 0 0
Italy
State/province [34] 0 0
Emilia-Romagna
Country [35] 0 0
Italy
State/province [35] 0 0
Lazio
Country [36] 0 0
Italy
State/province [36] 0 0
Liguria
Country [37] 0 0
Italy
State/province [37] 0 0
Lombardia
Country [38] 0 0
Italy
State/province [38] 0 0
Piemonte
Country [39] 0 0
Italy
State/province [39] 0 0
Veneto
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Krasnodar
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Lipetsk
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Moscow
Country [43] 0 0
Russian Federation
State/province [43] 0 0
N.Novgorod
Country [44] 0 0
Russian Federation
State/province [44] 0 0
Orel
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Perm
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Saratov
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Smolensk
Country [48] 0 0
Russian Federation
State/province [48] 0 0
St. Petersburg
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Volgograd
Country [50] 0 0
Spain
State/province [50] 0 0
(Móstoles) Madrid
Country [51] 0 0
Spain
State/province [51] 0 0
Alcala de Henares
Country [52] 0 0
Spain
State/province [52] 0 0
Alicante
Country [53] 0 0
Spain
State/province [53] 0 0
Almería
Country [54] 0 0
Spain
State/province [54] 0 0
Badalona
Country [55] 0 0
Spain
State/province [55] 0 0
Barcelona
Country [56] 0 0
Spain
State/province [56] 0 0
Cartagena (Murcia)
Country [57] 0 0
Spain
State/province [57] 0 0
Córdoba
Country [58] 0 0
Spain
State/province [58] 0 0
Granada
Country [59] 0 0
Spain
State/province [59] 0 0
La Coruña
Country [60] 0 0
Spain
State/province [60] 0 0
La Laguna (Santa Cruz De Tenerife)
Country [61] 0 0
Spain
State/province [61] 0 0
Madrid
Country [62] 0 0
Spain
State/province [62] 0 0
Malaga
Country [63] 0 0
Spain
State/province [63] 0 0
Mataró
Country [64] 0 0
Spain
State/province [64] 0 0
Murcia
Country [65] 0 0
Spain
State/province [65] 0 0
San Sebastián
Country [66] 0 0
Spain
State/province [66] 0 0
Sevilla
Country [67] 0 0
Spain
State/province [67] 0 0
Valencia
Country [68] 0 0
Spain
State/province [68] 0 0
Vigo ( Pontevedra)
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Warwickshire
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Brighton
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Crumpsall, Manchester
Country [72] 0 0
United Kingdom
State/province [72] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
ViiV Healthcare
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Shionogi
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
GlaxoSmithKline
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01227824
Trial related presentations / publications
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
ViiV Healthcare
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01227824