Primary: safety and tolerability of belimumab in a pediatric population (5-17 y) with SLE.Secondary: PK, efficacy, quality of life.
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety and tolerability.
Secondary outcome
PK, efficacy (main: >=4 point reduction from baseline in SELENA SLEDAI score, No
worsening (increase of < 0.30 points from baseline) in Physician*s Global
Assessment, No new BILAG A organ domain score or 2 new BILAG B organ domain
scores compared with baseline) and quality of life.
Background summary
Recent and past studies consistently show that adult and pediatric SLE patients
have increased serum BLyS levels. In SLE, the elevation of BLyS may contribute
to the persistence of B-cell subsets that produce pathogenic auto-antibodies or
promote inflammation that would otherwise be subject to down regulation. Thus a
therapeutic strategy that involves an antagonist to BLyS may have therapeutic
benefit in SLE. Belimumab is a BLyS specific inhibitor and has been registered
for the treatment of adults with active SLE.
In general, pediatric SLE patients have more severe disease and thus higher
disease activity index on average than adults. Adult SLE subjects who presented
with more active disease performed better with belimumab. It is theorized based
on this, that belimumab will have a beneficial effect in the pediatric SLE
population.
The aim of the present study is to generate data on the effects of belimumab in
children with active SLE.
Study objective
Primary: safety and tolerability of belimumab in a pediatric population (5-17
y) with SLE.
Secondary: PK, efficacy, quality of life.
Study design
Multi-center, Randomized Parallel Group, Placebo-Controlled Double-Blind
Trial.
Part A: comparison between belimumab and placebo. Cohort 1 (12 subjects 12-17
y, belimumab:placebo=5:1) No further inclusion until PK is known. Thereafter
cohort 2 starts (similar to cohort 1, but 5-11 y) as well as cohort 3 (subjects
12-17 y, randomization 1:1). When PK and safety of cohort 2 is known: inclusion
of additional subjects 5-11 y in cohort 3.
Starting dose belimumab 10 mg/kg i.v. infusion (minimal duration 1 h), First 3
infusions every 2 weeks, thereafter every 4 weeks. Duration 48 weeks. Existing
anti-SLE treatment will be continued.
Part B: long-term open-label follow-up study for those who have completed part
A. All subjects treated with belimumab. Duration up to 10 y.
Part C: follow-up for those who did not complete part A. No study treatment.
Duration up to 10 y.
Approx. 100 patients.
Interim-analyses, see protocol page 81.
IDMC, see protocol page 91.
Intervention
Treatment with belimumab or (in part A) placebo.
Study burden and risks
Risk: adverse events of study treatment.
Burden: Study visits part A-B: every 2 weeks (3x), thereafter every 4 weeks.
Part C; every month (3x), yearly thereafter. Duration part A: approx. 1 year.
Part B and C: up to 10 years.
Belimumab infusions (or placebo in part A) every 2 weeks (3x) and thereafter
every 4 weeks. Duration at least 1 h.
Physical examination every 4 weeks.
Blood tests every 4 weeks, up to 10 ml/visit. 4x serial PK, 3 samples in 2-4 h.
Urine tests every visit.
ECG during screening.
Completion questionnaires (incl. suicidal thoughts).
Optional pharmacogenetic research (saliva).
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Listed location countries
Age
Inclusion criteria
• 5 to 17 years of age
• Have or have had in series, 4 or more of the ACR 11 criteria for the classification of SLE.
• Active SLE disease defined as a SELENA SLEDAI score >= 6 at screening.
• 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. See protocol page 29 for details.
• On a stable SLE treatment regimen. See protocol page 29 for details.
• Sexually active females: adequate method of contraception. See protocol page 30 for details.
Exclusion criteria
• Treatment with belimumab any time.
• Any B-cell targeted therapy, Abatacept or biologic investigational agent during the last year.
• 3 or more courses of systemic corticosteroids for concomitant conditions in the last year.
• Forbidden treatments within the last 30/60/90 days; see protocol pages 32-33for details.
• Active central nervous system lupus requiring therapeutic intervention within last 60 days.
• eGFR as calculated by Schwartz Formula <30 ml/min
• Subjects >= 12 years who have evidence of serious suicide risk. See protocol page 33 for details.
• Pregnancy or breastfeeding
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov; registratienummer n.n.b. |
| EudraCT | EUCTR2011-000368-88-NL |
| CCMO | NL40462.078.12 |