Clinical trial NCT01649765: Pediatric Lupus Trial of Belimumab Plus Background Standard Therapy
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Keywords: SLE Flare Index
SRI
belimumab
efficacy
safety
B lymphocyte
BLyS
SELENA SLEDAI
BILAG
Lupus
Systemic Lupus Erythematosus (SLE)
PGA
Pharmacokinetics
placebo
PRINTO
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Human Genome Sciences Inc., a GSK Company
First posted: 2012-07-25
Enrollment: 93
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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 ≥ 6). 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 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 (SELENA SLEDAI score ≥ 6).
* 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. (BENLYSTA® is a registered trademark of the GSK group of companies.)
* Treatment with any B cell targeted therapy (for example, rituximab) or an investigational biological agent in the past year.
* Have received anti-TNF therapy; Interleukin-1 receptor antagonist; IVIG; or plasmapheresis within 90 days of Day 0.
* Have received high dose prednisone or equivalent (\>1.5mg/kg/day) within 60 days of baseline.
* Have received intravenous (IV) cyclophosphamide within 60 days of Day 0.
* Have received any new immunosuppressive/immunomodulatory agent, anti-malarial agent within 60 days of baseline.
* 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.

Primary outcomes:
measure: Percentage of Participants With SLE Responder Index (SRI) Response at Week 52
timeFrame: Week 52
Secondary outcomes:
measure: Percentage of Participants Meeting Pediatric Rheumatology International Trials Organization (PRINTO)/ American College of Rheumatology (ACR) Juvenile SLE Response Evaluation Criteria for Improvement in Juvenile SLE at Week 52 Using Definition 1 and 2
timeFrame: Week 52
measure: Percent Change From Baseline in ParentGA at Week 52
timeFrame: Baseline (Day 0) and Week 52
measure: Percent Change From Baseline in PGA at Week 52
timeFrame: Baseline (Day 0) and Week 52
measure: Percent Change From Baseline in SELENA SLEDAI at Week 52
timeFrame: Baseline (Day 0) and Week 52
measure: Percent Change From Baseline in PedsQL Physical Functioning Domain Score at Week 52
timeFrame: Baseline (Day 0) and Week 52
measure: Percent Change From Baseline in Proteinuria at Week 52
timeFrame: Baseline (Day 0) and Week 52
measure: Percentage of Participants With a Sustained SRI Response
timeFrame: Up to 52 weeks
measure: Percentage of Participants With a Sustained ParentGA Response
timeFrame: Up to 52 weeks
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 60 weeks
measure: Maximum Concentration at Steady State (Cmax, ss) and Minimum Concentration at Steady State (Cmin, ss)
timeFrame: 28-days dosing interval at steady state
measure: Area Under Curve of Belimumab at Steady State (AUC, ss)
timeFrame: 28-days dosing interval at steady state
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Augusta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Bronx
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Rosario
country: Argentina
facility: GSK Investigational Site
state: Santa Fe
city: Capital Federal
country: Argentina
facility: GSK Investigational Site
city: Santa Fe
country: Argentina
facility: GSK Investigational Site
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Kagoshima
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: San Luis Potosí
country: Mexico
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Tolyatti
country: Russian Federation
facility: GSK Investigational Site
city: Esplugues De Llobregat. Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Bristol
country: United Kingdom
facility: GSK Investigational Site
city: Liverpool
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: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Brunner HI, Abud-Mendoza C, Viola DO, Calvo Penades I, Levy D, Anton J, Calderon JE, Chasnyk VG, Ferrandiz MA, Keltsev V, Paz Gastanaga ME, Shishov M, Boteanu AL, Henrickson M, Bass D, Clark K, Hammer A, Ji BN, Nino A, Roth DA, Struemper H, Wang ML, Martini A, Lovell D, Ruperto N; Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Safety and efficacy of intravenous belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial. Ann Rheum Dis. 2020 Oct;79(10):1340-1348. doi: 10.1136/annrheumdis-2020-217101. Epub 2020 Jul 22.
citation: Brunner HI, Abud-Mendoza C, Mori M, Pilkington CA, Syed R, Takei S, Viola DO, Furie RA, Navarra S, Zhang F, Bass DL, Eriksson G, Hammer AE, Ji BN, Okily M, Roth DA, Quasny H, Ruperto N. Efficacy and safety of belimumab in paediatric and adult patients with systemic lupus erythematosus: an across-study comparison. RMD Open. 2021 Sep;7(3):e001747. doi: 10.1136/rmdopen-2021-001747.
citation: Zhou X, Lee TI, Zhu M, Ma P. Prediction of Belimumab Pharmacokinetics in Chinese Pediatric Patients with Systemic Lupus Erythematosus. Drugs R D. 2021 Dec;21(4):407-417. doi: 10.1007/s40268-021-00363-2. Epub 2021 Oct 9.
citation: Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.