Pediatric Lupus Trial of Belimumab Plus Background Standard Therapy

NCT01649765 | Completed Phase 2 Results DMC

• 3 other identifiers: 1140552011-000368-882024-512730-15-00
• Study Type: interventional
• Target: 93
• Locations: 10 countries
• Sites: 32

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

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With SLE Responder Index (SRI) Response at Week 52

  SRI response is defined as \>=4 point reduction, from Baseline in safety of estrogen in lupus national assessment (SELENA) systemic lupus erythematosus disease activity index (SLEDAI) score, no worsening (increase of \<0.30 points from Baseline) in physician's global assessment (PGA) and no new British Isles Lupus Assessment Group of SLE clinics (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with Baseline. Analysis was performed using a logistic regression model for the comparison between belimumab and placebo with covariates treatment group, Baseline SELENA SLEDAI score (\<=12 vs. \>=13). Percentage of participants with SRI response at Week 52 of Part A were reported. Intent-to-Treat Population comprised of all participants who were randomized and treated with at least one dose of study agent in Part A. One participant had missing data at Baseline and therefore, could not be included in the analysis.

  Week 52

Secondary Outcomes (11)

• 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

  Week 52

• Percent Change From Baseline in ParentGA at Week 52

  Baseline (Day 0) and Week 52

• Percent Change From Baseline in PGA at Week 52

  Baseline (Day 0) and Week 52

• Percent Change From Baseline in SELENA SLEDAI at Week 52

  Baseline (Day 0) and Week 52

• Percent Change From Baseline in PedsQL Physical Functioning Domain Score at Week 52

  Baseline (Day 0) and Week 52

Study Arms (4)

Part A: Placebo

PLACEBO COMPARATOR

Participants received saline infusion (placebo) intravenously monthly for 48 weeks on a background of standard of care.

Other: Placebo

Part A: Belimumab 10 mg/kg

EXPERIMENTAL

Participants received 10 milligrams per kilograms (mg/kg) reconstituted solution intravenously monthly for 48 weeks on a background of standard of care.

Drug: Belimumab 10 mg/kg

Part B: Open-Label Belimumab

EXPERIMENTAL

Participants who entered Part B after completing 48 weeks of belimumab or placebo on a background of standard of care and the Week 52 assessments in Part A, received 10 mg/kg belimumab intravenously monthly up to 10 years from the first administration of belimumab.

Drug: Belimumab 10 mg/kg

Part C: Safety Follow-up Phase

NO INTERVENTION

Participants who entered Part C after discontinuing study intervention in Part A or Part B were included in this arm.

Interventions

Placebo OTHER

Placebo was administered

Also known as: Normal Saline

Part A: Placebo

Belimumab 10 mg/kg DRUG

Belimumab was administered.

Part A: Belimumab 10 mg/kg; Part B: Open-Label Belimumab

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Human Genome Sciences Inc., a GSK Company: collaborator

Study Sites (32)

GSK Investigational Site

Phoenix, Arizona, 85016, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20010, United States

Location

GSK Investigational Site

Augusta, Georgia, 30912, United States

Location

GSK Investigational Site

St Louis, Missouri, 63104, United States

Location

GSK Investigational Site

New York, New York, 10032, United States

Location

GSK Investigational Site

The Bronx, New York, 10467, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45229, United States

Location

GSK Investigational Site

Buenos Aires, C1270AAN, Argentina

Location

GSK Investigational Site

Rosario, 2000, Argentina

Location

GSK Investigational Site

Santa Fe, 5400, Argentina

Location

GSK Investigational Site

Calgary, Alberta, T3B 6A8, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 1X8, Canada

Location

GSK Investigational Site

Aichi, 474-8710, Japan

Location

GSK Investigational Site

Kagoshima, 890-8520, Japan

Location

GSK Investigational Site

Miyagi, 989-3126, Japan

Location

GSK Investigational Site

Tokyo, 113-8519, Japan

Location

GSK Investigational Site

San Luis Potosí City, 78240, Mexico

Location

GSK Investigational Site

Lima, Lima 27, Peru

Location

GSK Investigational Site

Lima, Lima 5, Peru

Location

GSK Investigational Site

Surco, Lima 33, Peru

Location

GSK Investigational Site

Lodz, 91-738, Poland

Location

GSK Investigational Site

Warsaw, 02-637, Poland

Location

GSK Investigational Site

Moscow, 119435, Russia

Location

GSK Investigational Site

Saint Petersburg, 194100, Russia

Location

GSK Investigational Site

Tolyatti, 445846, Russia

Location

GSK Investigational Site

Espluges de Llobregat, 08950, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Valencia, 46026, Spain

Location

GSK Investigational Site

Bristol, BS2 8BJ, United Kingdom

Location

GSK Investigational Site

Liverpool, L12 2AP, United Kingdom

Location

GSK Investigational Site

London, NW1 2PG, United Kingdom

Location

GSK Investigational Site

London, WC1N 3JH, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 32699034 BACKGROUND

• 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.

  PMID: 34531304 BACKGROUND

• 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.

  PMID: 34628605 BACKGROUND

• Arends EJ, Zlei M, Tipton CM, Cotic J, Osmani Z, de Bie FJ, Kamerling SWA, van Maurik A, Dimelow R, Gregan YI, Fox NL, Rabelink TJ, Roth DA, Sanz I, van Dongen JJM, van Kooten C, Teng YKO. Disruption of memory B-cell trafficking by belimumab in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2024 Sep 1;63(9):2387-2398. doi: 10.1093/rheumatology/keae286.

  PMID: 38775637 DERIVED

• 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.

  PMID: 33687069 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

belimumab; Saline Solution

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

This submission adds adverse event data for Parts B and C. The previously posted Part A results are otherwise unchanged, except for a minor cosmetic change. The Statistical Analysis Plan for Part A has not been amended since the 2018 (Part A results) submission. Protocol Amendment 8, included with this submission, has not been amended for Part A of the study.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: July 23, 2012
• First Posted: July 25, 2012
• Study Start: September 7, 2012
• Primary Completion: January 24, 2018
• Study Completion: September 30, 2025
• Last Updated: April 20, 2026
• Results First Posted: August 15, 2018

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.

Locations

AR (3); ME (1); US (7); GB (4); CA (2); JP (4); PL (2); RU (3); PE (3); ES (3)