The primary objective is to characterize the PK profile of belimumab 200 mg SC in pediatric SLE participants.The secondary objectives are to evaluate the safety and tolerability of belimumab 200 mg SC in pediatric SLE participants and to…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Observed belimumab concentrations at Week 12.
• Steady-state PK parameters: Cavg (AUC), Cmax, Cmin (based on population PK
estimates).
Secondary outcome
• Incidence of adverse events, serious adverse events and adverse events of
special interest through Week 52.
• Change from baseline in biomarkers (C3/C4, anti-dsDNA, B cell subsets, and
immunoglobulins) at Weeks 12 and 52.
• Percent of subjects with a >= 4 point reduction from baseline in SELENA SLEDAI
at Weeks 12 and 52.
Background summary
The purpose of this study is to evaluate the pharmacokinetics (PK), safety, and
pharmacodynamics (PD) of repeat doses of 200 mg belimumab administered
subcutaneously (SC) in pediatric participants 5 to 17 years of age with
systemic lupus erythematosus (SLE) on a background of standard of care therapy.
This bridging PK study is part of an extrapolation strategy to support the use
of SC belimumab in pediatric SLE patients, based on the completed adult SLE
study with SC belimumab and the pediatric SLE study with IV belimumab, and is a
component of a post-approval commitment to EMA (EMA-000520-PIP02-13-M01) and
FDA (postmarketing requirement 3239-1 under BLA 761043)
Study objective
The primary objective is to characterize the PK profile of belimumab 200 mg SC
in pediatric SLE participants.
The secondary objectives are to evaluate the safety and tolerability of
belimumab 200 mg SC in pediatric SLE participants and to characterize the
pharmacodynamic profile of SC belimumab 200 mg SC in pediatric SLE
participants. Another objective is to characterize the impact on disease
activity of belimumab 200 mg SC in pediatric SLE participants.
Study design
This is a single arm, multi-center open-label study to evaluate the PK, safety,
and PD of SC belimumab plus background standard therapy in approximately 24
pediatric participants ages 5 to 17 years of age and weighing at least 5 kg
with active SLE. The study will include:
• Part A: Open-label, 12-week treatment phase.
• Part B: Optional 40-week open-label continuation phase for any participant
who completes Part A.
• Post-treatment follow-up assessments at 8 and 16 weeks after the last dose of
SC belimumab.
• Optional Access Extension Phase: Optional post-Week 52 extension phase
exclusively for eligible participants who complete Part B (e.g., participants
from countries where the IV formulation is not approved for pediatric use; or
participants in whom IV Benlysta is not suitable due to medical reasons or
significant logistical challenges).
Intervention
The total maximum duration of study participation for each participant is 73
weeks (screening:5 weeks, treatment: up to 52 weeks [12 weeks Part A plus 40
weeks extension phase] and follow-up: 16 weeks).
Cohort 1 will include participants >50 kg body weight, Cohort 2 will include
participants <30 to <50 kg body weight and Cohort 3 will include participants
<30 kg body weight at baseline. In Part A Cohort 1 will receive weekly doses of
belimumab 200 mg SC, Cohort 2 will receive belimumab 200 mg SC every 10 days
and Cohort 3 will receive belimumab 200 mg SC every 2 weeks.
In Part B, the dosing frequency may change according to pre-defined criteria
based on changes in body weight of the participant.
The optional access extension phase is to provide a mechanism for continued
access to belimumab SC from Week 52 onwards. The duration of this optional
access extension phase will depend on age of the participants and the
conditions for eligibility. During the access extension phase, the dosing
frequency may change based on changes in body weight of the participant.
Participants who are
enrolled into the optional access extension phase will be withdrawn from
treatment if they reach the age of 18 years, if Belimumab SC or IV becomes
licensed and commercially available for pediatric use in the Netherlands.
Study burden and risks
The study is using belimumab SC in the pediatric population, thereby allowing
patients the potential to administer their medication at home, and decreasing
the burden of visits to an infusion center.
Risk: Adverse events of the study medication.Overall, the positive benefit/risk
profile of IV belimumab in the BEL114055 pediatric SLE population appears
consistent with that of adult IV and SC study populations.
Burden:
Screening period: one (cohort 1&2) or two (cohort 3) visits to the clinic
including • blood (27 ml) and urine collection, • pregnancy test (if
appropriate), • lupus disease activity assessment, • general health status
evaluation incl. physical examination and ECG, • training in use auto-injector.
Part A 12 weeks treatment: 6 visits to the clinic over a 12-week period
including • blood (all visits, often 7 or 20 ml per visit and at day 1 21 ml)
and urine (most visits) collection for safety testing, measuring the quantity
of belimumab in the blood and/or evaluation of the effects of belimumab, •
pregnancy test (all visits, if appropriate), general health status evaluation
incl. physical examination (all visits), • lupus disease activity assessment
(once at the beginning and once at the end). Depending on weight: weekly, every
10 days or bi-weekly injections (1 ml using auto-injector) and completion of
injection diary.
Part B optional 40 weeks treatment: 7 visits to the clinic over a 40-week
period including • blood (all visits, often 7 or 20 ml per visit) and urine
(most visits) collection for safety testing, measuring the quantity of
belimumab in the blood and/or evaluation of the effects of belimumab, •
pregnancy test (all visits, if appropriate), general health status evaluation
incl. physical examination (all visits), • lupus disease activity assessment
(once at the end). Depending on weight: weekly, every 10 days or bi-weekly
injections and completion of injection diary.
8 weeks post treatment visit to the clinic: • blood (20 ml) and urine
collection, • pregnancy test (if appropriate), • general health status
evaluation incl. physical examination
16 weeks post treatment phone call from the clinic: • pregnancy test (if
appropriate), • general health status evaluation
In the optional extension phase, after the week 52 visit, participants will
return to the clinic every 12 weeks for weight measurement, pregnancy test (if
applicable), and finally general health status evaluation. At the 8- and
16-week follow-up visits, SAEs and the results of home urine pregnancy test
will be collected by phone (if applicable). The 8-week and 16-week follow-up
may be performed at a clinic visit, per local requirement.
Van Asch van Wijckstraat 55H
Amersfoort 3811 LP
NL
Van Asch van Wijckstraat 55H
Amersfoort 3811 LP
NL
Listed location countries
Age
Inclusion criteria
For parts A and B of the study
1. Participants between 5 and 17 years of age inclusive, at the time of Day 1.
2. SLE according to the ACR criteria (at least 4/11 criteria). (Appendix 9 of
the protocol)
3. Screening SLEDAI-2K score >=6 (total score). (Appendix 10 of the protocol.)
4. Have unequivocally documented positive autoantibody test results. See
protocol page 48 for details.
5. Stable SLE treatment regimen consisting of any of the following medications
(alone or in combination) for a period of at least 30 days prior to Day 1:
corticosteroids, immunosuppressants, anti-malarials, NSAIDs. See protocol page
48-49 for details.
6. Body weight >=15 kg.
7. Male and/or female participants. Female participant of childbearing
potential who agrees to follow the contraceptive guidance in appendix 4 of the
protocol during the treatment period and for at least 16 weeks after the last
dose of belimumab.
8. Participant signs and dates a written age appropriate assent form/ informed
consent form and the parent(s) or legal guardian provides written informed
consent for minors between 5 and 16 year old.
Optional Access Extension
1. Male or female participants who complete Week 52 visit of the 200908 study.
2. Age <18 years at completion of Week 52.
3. Documented evidence of clinical benefit in 200908 study per investigator*s
judgement.
4. Able to comply with clinic visits and required assessments.
5. Intravenous (IV) Benlysta not currently licensed for the pediatric use in
the participant*s country; OR documented evidence of the rationale for IV
Benlysta not being suitable for this participant requiring continued treatment
with belimumab SC.
6. Participant eligibility agreed with the Medical Monitor prior to enrolling
the participant into the optional access extension phase.
7. Participant signs and dates a written age appropriate assent form specific
for the access extension phase and the parent or legal guardian (or emancipated
minor), provides written informed consent specific to the access extension.
Exclusion criteria
For parts A + B of the study
1. eGFR of less than 30 mL/min
2. Acute severe nephritis defined as significant renal disease. See protocol
page 50 for details.
3. History of a major organ transplant or hematopoetic stem cell/marrow
transplant.
4. Clinical evidence of significant, unstable or uncontrolled, acute or
chronic diseases not due to SLE. See protocol page 50 for details.
5. Planned surgical procedure or a history of any other medical disease ,
laboratory abnormality, or condition that, in the opinion of the investigator,
makes the participant unsuitable for the study.
6. History of malignant neoplasm within the last 5 years.
7. Evidence of serious suicide risk including any history of suicidal behavior
in the last 6 months, or who in the investigator*s opinion, pose a significant
suicide risk.
8. History of a primary immunodeficiency.
9. IgA deficiency (IgA level <10 mg/dL).
10. Acute or chronic infections requiring management, See protocol page 44 for
details.
11. Grade 3 or greater laboratory abnormality (Page 51 and Appendix 2, Section
10.2.1 of the protocol).
12. History of an anaphylactic reaction to parenteral administration of
contrast agents, human or murine proteins or monoclonal antibodies,or to any of
the excipients of the study drug
13. Ever received treatment with belimumab (BENLYSTA).
14. Received any of the following within 364 days of Day 1: - Treatment with
any B-cell targeted therapy, - Abatacept, - Any biologic investigational agent.
See protocol page 51/60 for details.
15. 3 or more courses of systemic corticosteroids for concomitant conditions
within 90 days of Day 1
16. Received any of the following within 90 days of Day 1: - Anti-TNF therapy,
- Interleukin-1 receptor antagonist, - IV immunoglobulin, - Plasmapheresis.
17. Received any of the following within 30 days of Day 1: - IV
cyclophosphamide, - A non-biologic investigational agent, - Any new
immunosuppressive/immunomodulatory agent, - High dose prednisone or equivalent
(>1.5 mg/kg/day) or any i.m.or i.v. steroid injection.
18. Have received a live or live-attenuated vaccine within 30 days of Day 1.
19. Have active CNS lupus requiring therapeutic intervention within 60 days of
Day 1.
20. Have required renal replacement therapy within 90 days of Day 1 or are
currently on renal replacement therapy.
21. Participation in an interventional clinical study either concurrently or
within 6 months of screening. Participation in an observational study may be
permitted.
22/23/24. Positive HIV, hepatitis B or C test. See protocol p 45 for details
25. Have current drug or alcohol abuse or dependence, or a history of drug or
alcohol abuse or dependence within 364 days prior to Day 1.
26. Are unable or unlikely, in the opinion of the investigator, to administer
belimumab by SC injection and have no reliable source to administer the
injection.
27. Children in Care. See protocol page 53 for details.
- Pregnancy/breastfeeding
Optional Access Extension
1. Female participant has positive urine pregnancy test at Week 52 visit.
2. Female participant wishes to become pregnant at or within 4 months of Week
52 visit.
3. Participant has experienced any change in his/her medical history that, per
the investigator*s judgement, continued administration of belimumab therapy
would be contraindicated.
4. Participant received a live vaccine within 30 days prior to Week 52
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 |
|---|---|
| EudraCT | EUCTR2018-004645-16-NL |
| CCMO | NL71295.078.19 |
| Other | www.gsk-clinicalstudyregister.com; 200908 |