A clinical research study to evaluate the effect of belimumab for the treatment of Systemic Lupus Erythematosus (SLE) in paediatric patients 5 to 17 years of age

• Register: EUCTR
• Last refreshed on: 10 August 2020
• Main ID: EUCTR2011-000368-88-GB
• Date of registration: 18/04/2012
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Ltd
• Public title: A clinical research study to evaluate the effect of belimumab for the treatment of Systemic Lupus Erythematosus (SLE) in paediatric patients 5 to 17 years of age
• Scientific title: A Multi-center, Randomized Parallel Group, Placebo-Controlled Double-Blind 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 (SLE) - Belimumab in pediatric patients with SLE
• Date of first enrolment: 13/06/2012
• Target sample size: 100
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000368-88
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Open label long-term extension; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Brazil, Canada, Italy, Mexico, Netherlands, Peru, Poland, Russian Federation, Spain, United Kingdom, United States

Contacts

• Name: GSK Clinical Helpdesk Support
• Affiliation: GlaxoSmithKline Research & Development Ltd

• Name: GSK Clinical Helpdesk Support
• Affiliation: GlaxoSmithKline Research & Development Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Are 5 to 17 years of age
2. Have or have had in series, 4 or more of the American College of Rheumatology (ACR) 11 criteria for the classification of SLE
3. Have active SLE disease defined as a SELENA SLEDAI score = 8 at screening.
4. Have unequivocally positive autoantibody test results defined as an ANA titre = 1:80
and/or a positive anti-dsDNA (= 30 IU/mL) serum antibody test from 2 independent
Time points as follows:
•Positive test results from 2 independent time points within the study screening
period. Screening results must be based on the study’s central laboratory results.
OR
•One positive historical test result and 1 positive test result during the screening period.
Historical documentation of a positive test of ANA (e.g., ANA by HEp-2 titre) or antidsDNA (e.g., anti-dsDNA by Farr assay) must include the date and type of the test, the name of the testing laboratory, numerical reference range, and a key that explains values provided as positive vs. negative OR negative, equivocal/borderline positive). Only unequivocally positive values as defined in the laboratory’s reference range are acceptable; borderline values will not be accepted.
5. Are on a stable SLE treatment regimen.
“Stable treatment at baseline” consists of any of the following medications (alone or in combination) at a fixed dose for a period of at least 30 days prior to Day0:
• Corticosteroids (prednisone or prednisone equivalent up to 0.5 mg/kg/day):
• For subjects on SLE combination therapy, their stable steroid dose must be fixed within the range of 0 to 0.5mg/kg/day (prednisone or prednisone equivalent)
• For subjects whose only SLE treatment is steroids, their stable steroid
dose must be fixed within the range of 0.1-0.5mg/kg/day.
• For those subjects on alternating day doses of steroids, use the average of 2 daily doses to calculate the average daily steroid dose.
• Other immunosuppressive or immunomodulatory agents including methotrexate, azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil, mycophenolate mofetil hydrochloride, and mycophenolate sodium), calcineurin inhibitors (e.g. tacrolimus, cyclosporine), sirolimus, oral cyclophosphamide, 6-mercaptopurine or thalidomide.
• Anti-malarials (e.g. hydroxychloroquine, chloroquine, quinacrine)
• Non-steroidal anti-inflammatory drugs (NSAIDs)
Note:
• Pre-existing SLE medications must be stable for at least 30 days prior to Day 0.
• Corticosteroids may be added as new medications or their doses adjusted only up to 30 days prior to Day 0.
• New SLE therapy other than corticosteroids must not be added within 60 days of Day 0.

(For the full section on Inclusion criteria, please refer to the Protocol on Page 28-31)
Are the trial subjects under 18? yes
Number of subjects for this age range: 100
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Have received treatment with belimumab (BENLYSTA™) at any time
2. Have received any of the following within 364 days of Day 0:
•Treatment with any B-cell targeted therapy (e.g., rituximab, other anti-CD20 agents, anti- CD22 [epratuzumab], anti-CD52 [alemtuzumab], BLyS-receptor fusion protein [BR3], TACI-Fc)
•Abatacept.
A biologic investigational agent
3. Have required 3 or more courses of systemic corticosteroids for concomitant conditions (e.g., asthma, atopic dermatitis) within 364 days of Day 0 (Topical or inhaled steroids are permitted).
4. Have received intravenous IV cyclophosphamide within 90 days of Day 0.
5. Have received any of the following within 90 days of Day 0:
• Anti-TNF therapy (e.g., adalimumab, etanercept, infliximab).
• Interleukin-1 receptor antagonist (anakinra).
• Intravenous immunoglobulin (IVIG).
• Plasmapheresis.
6. Have received any of the following within 60 days of Day 0:
• A non-biologic investigational agent
• Any new immunosuppressive/immunomodulatory agent, anti-malarial, NSAID, (See Inclusion Criteria #5)
Note: New inhaled steroids and new topical immunosuppressive agents (e.g., eye drops, topical creams) are allowed. Any NSAID use for < 1 week is allowed
• High dose prednisone (> 1.5 mg/kg/day) or equivalent or any steroid injection (IM, IA, IV)
7. Have received any of the following within 30 days of Day 0:
• A live vaccine.
•A change in dose of a corticosteroid, other immunosuppressive/ immunomodulatory agent, anti-malarial, NSAID, (See Inclusion Criteria #5)
8. Have active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident [CVA], cerebritis or CNS vasculitis) requiring therapeutic intervention within 60 days of Day 0.
9. Have required renal replacement therapy (e.g. hemodialysis, peritoneal dialysis) within 90 days of Day 0 or be currently on renal replacement therapy
10. Have an estimated glomerular filtration rate (eGFR) as calculated by Schwartz Formula of less than 30 ml/min.
11. Have severe nephritis defined as a significant worsening of renal disease manifested by the presence of urinary sediments and other lab abnormalities that, in the opinion of the study investigator, may lead to the subject requiring IV cyclophosphamide, MMF or high dose IV corticosteroids during the first 6 months of the trial.View protocol for further information.
12. Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or
hematopoetic stem cell/marrow transplant.
13. Have clinical evidence of significant, unstable or uncontrolled, acute or chronic
diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases) which, in the opinion of the principal investigator, could confound the results of the
study or put the subject at undue risk.
14. Have a planned surgical procedure or a history of any other medical disease (e.g. cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion of the principal investigator, makes the subject unsuitable for the study.
15. Have a history of malignant neoplasm within the last 5 years.
16. Subjects => 12 years of age who have evidence of serious suicide risk including any
history of suicidal behaviour in the last 6 months and/or any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (Refer to Appendix 12 w

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus
MedDRA version: 21.1 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name: BENLYSTA™ (belimumab)
Product Name: Benlysta (belimumab)
Product Code: GSK1550188
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: belimumab
CAS Number: 356547-88-1
Current Sponsor code: GSK1550188
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 80-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: • Evaluate the safety and tolerability of belimumab in the pediatric SLE population
• Evaluate the pharmacokinetics of belimumab in the pediatric SLE population.
• Evaluate the efficacy of belimumab in the pediatric SLE population
• Evaluate the effects of belimumab on the quality of life in the pediatric SLE population.

Primary end point(s): The primary efficacy endpoint is SLE
Responder Index (SRI) response rate at
Week 52 which is defined as:
= 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 Objective: •To evaluate the sustained efficacy and safety of belimumab in the pediatric SLE population
•Evaluate the pharmacokinetics of belimumab in the pediatric SLE population
•Evaluate the effects of belimumab on the quality of life and fatigue in the pediatric SLE population

Timepoint(s) of evaluation of this end point: 52 weeks

Secondary Outcome(s)

Secondary end point(s): 1. 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 below and no more than 1 of the remaining worsening by more than 30%
b. At least 30% improvement in 3 of 5endpoints below and no more than of the remaining worsening more than 30%.
I. Percent change in Parent’s Global Assessment (ParentGA) at Week 52.
II. Percent change in Physician’s Global Assessment (PGA) at Week 52.
III. Percent change in SELENA SLEDAI score at Week 52.
IV. Change in PedsQL physical functioning domain at Week 52
V. Percent change in 24 hour proteinuria at Week 52 (g/24hour equivalent by spot urine protein to creatinine ratio).
2. Proportion of subjects with a sustained SRI response
3. Proportion of subjects with a sustained ParentGA response
4. Safety of belimumab
5. PK comparison with Adult PK
6. PedsQL Multidimensional Fatigue Scale

Timepoint(s) of evaluation of this end point: 52 weeks

Secondary ID(s)

BEL114055

Source(s) of Monetary Support

GlaxoSmithKline, Research and Development Ltd

Ethics review

Status: Approved
Approval date: 13/06/2012
Contact:

Results

• Results available: Yes
• Date Posted: 08/08/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-000368-88/results