Trial record 16 of 38 for:    " October 06, 2010":" November 05, 2010"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

A Trial Comparing GSK1349572 50mg Once Daily to Raltegravir 400mg Twice Daily (SPRING-2)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Shionogi
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT01227824
First received: October 14, 2010
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Infection, Human Immunodeficiency Virus I
Drug: GSK1349572 (dolutegravir)
Drug: raltegravir
Other: GSK1349572 Placebo
Other: ABC/3TC
Other: TDF/FTC
Other: raltegravir Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by ViiV Healthcare:

Primary Outcome Measures:
  • Percentage of Participants With HIV-1RNA <50 Copies (c)/Milliliter (mL) Through Week 48. [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance. [ Time Frame: Week 48 and Week 96 ] [ Designated as safety issue: No ]
    Number of participants with detectable virus that has genotypic or phenotypic evidence of Integrase Inhibitor (INI) resistance were assessed at Week 48 and Week 96. Integrase inhibitors are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the deoxyribonucleic acid (DNA) of the host cell.

  • Number of Participants With Plasma HIV-1 RNA <50 c/mL [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    The number of participants with plasma HIV-1 RNA level <50 c/mL was assessed at Week 96.

  • Number of Participants With Plasma HIV-1 RNA <400 c/mL [ Time Frame: Week 48 and Week 96 ] [ Designated as safety issue: No ]
    The number of participants with plasma HIV-1 RNA level <400 c/mL was assessed at Week 48 and Week 96.

  • Change From Baseline in Plasma HIV-1 RNA Over Time [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, and 96 ] [ Designated as safety issue: No ]
    Change from baseline in plasma HIV-1 RNA over time was assessed at Baseline, Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, and 96. Change from baseline was calculated as the post-Baseline value minus the Baseline value.

  • Absolute Values in Plasma HIV-1 RNA Over Time [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, and 96 ] [ Designated as safety issue: No ]
    Absolute values in plasma HIV-1 RNA over time was assessed at Baseline, Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, and 96.

  • Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, and 96 ] [ Designated as safety issue: No ]
    CD4 lymphocyte cells (also called T-cells or T-helper cells) are the primary targets of HIV. The CD4 count and the CD4 percentage mark the degree of immunocompromise. The CD4 count is used to stage the patient's disease, determine the risk of opportunistic illnesses, assess prognosis, and guide decisions about when to start antiretroviral therapy. Changes from Baseline in CD4+ cell counts over time was assessed at Baseline, Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, and 96. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

  • Absolute Values in CD4+ Cell Counts Over Time [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, and 96 ] [ Designated as safety issue: No ]
    CD4 lymphocyte cells (also called T-cells or T-helper cells) are the primary targets of HIV. The CD4 count and the CD4 percentage mark the degree of immunocompromise. The CD4 count is used to stage the patient's disease, determine the risk of opportunistic illnesses, assess prognosis, and guide decisions about when to start antiretroviral therapy.bsolute values in CD4+ cell counts over time was assessed at Baseline, Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, and 96.

  • Number of Participants With the Indicated Post-baseline HIV-associated Conditions and Progression, Excluding Recurrences [ Time Frame: From Baseline until Week 96 ] [ Designated as safety issue: No ]
    Clinical disease progression (CDP) was assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the AIDS surveillance case definition. Indicators of CDP were defined as: CDC CAT A at Baseline (BS) to a CDC CAT C event (EV); CDC CAT B at BS to a CDC CAT C EV; CDC CAT C at BS to a new CDC CAT C EV; or CDC CAT A, B, or C at BS to death.

  • Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) [ Time Frame: From Baseline until Week 96 ] [ Designated as safety issue: No ]
    All Grade 1 to 4 post-Baseline-emergent chemistry toxicities included alanine aminotransferase (ALT), alkaline phosphatase (ALP), asparate aminotransferase (AST), carbon dioxide (CO2) content/bicarbonate, cholesterol, creatine kinase (CK), creatinine, hyperglycemia, hyperkalemia, hypernatremia, hypoglycemia, hypokalemia, hyponatremia, low density lipoprotein (LDL) cholesterol calculation, lipase, phosphorus inorganic, total bilirubin, and triglycerides. All Grade 1 to 4 post-Baseline-emergent hematology toxities included hemoglobin, platelet count, total neutrophils, and white blood cell count. The Division of AIDS (DAIDS) defined toxicity grades as follows: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening; Grade 5, death.

  • AUC(0-tau) of DTG [ Time Frame: Week 4, Week 24, and Week 48 ] [ Designated as safety issue: No ]
    AUC is defined as the area under the DTG concentration-time curve as a measure of drug exposure over time. AUC(0-tau) is defined as the area under the plasma concentration-time curve from time zero to time tau over a dosing interval at steady state, where tau is the length of the dosing interval of DTG. The predicted individual AUC(0-tau) were obtained from the final population PK model by an empirical Bayes estimation. Blood samples for pharmacokinetic assessments were collected at pre-dose (within 15 minutes prior to dose) at Week 4, Week 24, and Week 48 and 1 to 3 hours post-dose or 4 to 12 hours post-dose at Week 4 and Week 24. If 1 to 3 hours post-dose was completed at Week 4, then the 4 to12 hour post-dose must be obtained at Week 48, and vice versa. AUC was estimated using population PK modeling based on PK data from all visits.

  • Cmax and Ctau of DTG [ Time Frame: Week 4, Week 24, and Week 48 ] [ Designated as safety issue: No ]
    The maximum plasma concentration (Cmax) and concentration at the end of a dosing interval (Ctau) of DTG were assessed at Week 48. The predicted individual Cmax and Ctau were obtained from the final population PK model by simulation of the concentration-time profiles. Blood samples for pharmacokinetic assessments were collected at pre-dose (within 15 minutes prior to dose) at Week 4, Week 24, and Week 48 and 1 to 3 hours post-dose or 4 to 12 hours post-dose at Week 4 and Week 24. If 1 to 3 hour post-dose was completed at Week 4, then the 4 to12 hour post-dose must be obtained at Week 48, and vice versa.


Enrollment: 827
Study Start Date: October 2010
Estimated Study Completion Date: June 2015
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK1349572 (N=~394)
GSK1349572 50mg once daily + raltegravir placebo twice daily + NRTI background therapy once daily
Drug: GSK1349572 (dolutegravir)
GSK1349572 50 mg taken once daily with or without food
Other: GSK1349572 Placebo
GSK1349572 placebo taken once daily
Other: ABC/3TC
Abacavir/Lamivudine background therapy once daily
Other: TDF/FTC
Tenofovir/emtricitabine background therapy once daily
Active Comparator: raltegravir (N=~394)
raltegravir 400mg twice daily + GSK1349572 placebo once daily + NRTI background therapy once daily
Drug: raltegravir
raltegravir 400mg taken twice daily
Other: ABC/3TC
Abacavir/Lamivudine background therapy once daily
Other: TDF/FTC
Tenofovir/emtricitabine background therapy once daily
Other: raltegravir Placebo
raltegravir placebo taken twice daily

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01227824

  Show 101 Study Locations
Sponsors and Collaborators
ViiV Healthcare
Shionogi
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials ViiV Healthcare
  More Information

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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT01227824     History of Changes
Other Study ID Numbers: 113086
Study First Received: October 14, 2010
Results First Received: August 15, 2013
Last Updated: June 19, 2014
Health Authority: Spain: Agencia Española del Medicamento y Productos Sanitarios
Australia: Human Research Ethics Committee
Russia: Federal Service of Surveillance in Healthcare and Social development of Russian federation
United States: Food and Drug Administration
Russia: Russian Ministry of Health
Canada: Health Canada
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Europe: European Medicines Agency

Keywords provided by ViiV Healthcare:
integrase inhibitor
HIV Infection
raltegravir
GSK1349572

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Reverse Transcriptase Inhibitors
Integrase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014