Pediatric Lupus Trial of Belimumab Plus Background Standard Therapy (PLUTO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by GlaxoSmithKline
Sponsor:
Collaborator:
Human Genome Sciences Inc., a GSK Company
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01649765
First received: July 23, 2012
Last updated: October 9, 2014
Last verified: October 2014
  Purpose

This is a multi-center study to evaluate the safety, pharmacokinetics, and efficacy of belimumab intravenous (IV) in pediatric patients 5 to 17 years of age with active systemic lupus erythematosus


Condition Intervention Phase
Systemic Lupus Erythematosus
Drug: belimumab 10mg/kg
Other: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Placebo-Controlled Trial to Evaluate the Safety, Efficacy, and Pharmacokinetics of Belimumab, a Human Monoclonal Anti-BLyS Antibody, Plus Standard Therapy in Pediatric Patients With Systemic Lupus Erythematosus

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • SLE Response Index (SRI) [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    >/=4 point reduction from baseline in SELENA SLEDAI score, and No worsening (increase of < 0.30 points from baseline) in Physician's Global Assessment (PGA), and No new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with baseline.


Secondary Outcome Measures:
  • Proportion of subjects meeting PRINTO/ACR Juvenile SLE Response Evaluation criteria for improvement in juvenile SLE [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    Proportion of subjects meeting PRINTO/ACR Juvenile SLE Response Evaluation criteria for improvement in juvenile SLE using two different PRINTO/ACR Juvenile SLE Response Evaluation definitions of improvement. a. At least 50% improvement in any 2 of 5 endpoints and no more than 1 of the remaining worsening by more than 30%. 1. Percent change in Parent's Global Assessment (ParentGA). 2. Percent change in Physician's Global Assessment (PGA). 3. Percent change in SELENA SLEDAI score. 4. Change in PedsQL physical functioning domain. 5. Percent change in 24 hour proteinuria.

  • Proportion of subjects with a sustained SRI response [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    Proportion of subjects with a sustained SRI response (defined as having a response on the primary efficacy endpoints at Weeks 44, 48, and 52)

  • Proportion of subjects with a sustained Parent Global Assessment response [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    Proportion of subjects with a sustained Parent Global Assessment response (defined as having >0.7 improvement at Weeks 44, 48, and 52 compared at baseline).

  • Number and percent of subjects with Adverse Events (AEs) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    All adverse events, severity, study agent related events, AEs leading to permanent discontinuation of study agent.

  • Number and percent of subjects with Serious Adverse Events (SAEs) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    All Serious Adverse Events, severity, study agent related events, SAEs leading to permanent discontinuation of study agent, SAEs resulting in death.

  • Summary of Pharmacokinetics Profile (AUC, Cmax, Cmin) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    AUC, Cmax, Cmin compared to adult Pharmacokinetics


Estimated Enrollment: 100
Study Start Date: September 2012
Estimated Study Completion Date: January 2027
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
belimumab 10mg/kg IV monthly
Drug: belimumab 10mg/kg
belimumab 10mg/kg IV monthly
Placebo Comparator: Arm 2
Normal Saline IV monthly
Other: placebo
Normal Saline 250 ml
Other Name: Normal Saline

Detailed Description:

This is a multi-center study to evaluate the safety, pharmacokinetics, and efficacy of belimumab intravenous (IV) in pediatric patients 5 to 17 years of age with active systemic lupus erythematosus (SELENA SLEDAI score ≥8). The study will consist of three phases: a 52-week randomized, placebo-controlled, double-blind phase; a long term open label continuation phase; and a long term safety follow up phase. The long term open label continuation and safety follow up periods will continue for at least 5 years and possibly up to 10 years from a subject's initial treatment with belimumab. Enrolment will be staggered by age cohorts to allow safety and PK interim analyses. Subjects will be randomized to belimumab 10mg/kg or placebo IV monthly dosing while continuing to receive background standard therapy throughout the study. An independent data monitoring committee (IDMC) will monitor the study as it progresses.

  Eligibility

Ages Eligible for Study:   5 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 5 years to 17 years of age at enrollment
  • Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) classification criteria.
  • Have active SLE disease.
  • Have positive anti-nuclear antibody (ANA) test results.
  • Are on a stable SLE treatment regimen at a fixed dose for a period of at least 30 days prior to Day 0.
  • Females of childbearing age are willing to use appropriate contraception
  • Subject age appropriate assent and parent or legal guardian informed consent to participate

Exclusion Criteria:

  • Pregnant or nursing.
  • Have received treatment with belimumab (BENLYSTA™) at any time.
  • Treatment with any B cell targeted therapy (for example, rituximab) or an investigational biological agent in the past year.
  • Have received intravenous (IV) cyclophosphamide within 90 days of Day 0.
  • Have severe lupus kidney disease.
  • Have active central nervous system (CNS) lupus.
  • Have had a major organ transplant.
  • Have significant unstable or uncontrolled acute or chronic diseases or conditions not due to SLE.
  • Have a planned surgical procedure.
  • History of malignant neoplasm within the last 5 years.
  • Have required management of acute or chronic infections in the past 60 days.
  • Have current drug or alcohol abuse or dependence.
  • Have a historically positive test, or test positive at screening for HIV, Hepatitis B, or Hepatitis C.
  • Have an IgA deficiency.
  • Have severe laboratory Abnormalities.
  • Have had anaphylactic reaction to X-ray contrast agents or biologic agents.
  • Suicidal behavior or ideation.
  • Children in Care(CiC): a child who has been placed under the control or protection of an agency, organisation, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation.
  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: NCT01649765

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

  Show 32 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Human Genome Sciences Inc., a GSK Company
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01649765     History of Changes
Other Study ID Numbers: 114055
Study First Received: July 23, 2012
Last Updated: October 9, 2014
Health Authority: Spain: Agencia Espanola de Medicamentos y Productos Sanitarios
Italy: Comitato di Etica IRCCS Instituto Giannina Gaslini di Genova
Peru: Ministry of Health
Netherlands: Centrale Commissie Mensgebonden Onderzoek
Poland: URZAD REJESTRACJI PRODUKTOW LECZNICZYCH, WYROBOW MEDYCZNYCH I PRODUKTOW BIOBOJCZYCH
United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Mexico: Ministry of Health
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
Pharmacokinetics
safety
SLE Flare Index
SRI
BLyS
SELENA SLEDAI
Lupus
belimumab
PRINTO
BILAG
efficacy
placebo
PGA
Systemic Lupus Erythematosus (SLE)
B lymphocyte

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Belimumab
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 21, 2014