Systemic Lupus Erythematosus
Conditions
Keywords
Human immunoglobulin (Ig) G1κ monoclonal antibody (mAb) directed against subunit 1 of the type I interferon (IFN) receptor, Accessorized pre-filled syringe, Pharmacokinetics, Pharmacodynamics
Brief summary
The purpose of this study is to characterize the pharmacokinetics (PK), pharmacodynamics (PD), and safety of subcutaneous (SC) anifrolumab in pediatric participants with moderate to severe systemic lupus erythematosus (SLE) while on background standard of care (SoC) therapy.
Detailed description
This is an open-label, multicenter study. The study includes - * Screening Period of up to 35 days * Period A (12-week, open-label treatment period) * Period B (a possible 12-week dosing regimen adjustment period, if required) * Treatment Extension Period (up-to-40-week, optional) * Period C (a 12-week safety follow-up period) The study intervention (anifrolumab) will be administered subcutaneously using an accessorized pre-filled syringe (APFS) in 2 cohorts.
Interventions
COMBINATION_PRODUCTAnifrolumab + APFS
Anifrolumab will be administered as a SC injection using an APFS.
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of SLE. * Must be receiving at least one of the following SoC regimens for ≥ 4 weeks: oral glucocorticoids (≤1.0 mg/kg/day or ≤ 40 mg/day prednisone equivalent), antimalarials (hydroxychloroquine, chloroquine, or quinacrine), or a single permitted immunosuppressant (azathioprine, mycophenolate mofetil/mycophenolic acid, methotrexate, mizoribine, or tacrolimus) within specified dose limits. * Participant must have moderate to severe active SLE disease defined as Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) ≥ 6 total points. * Body weight ≥ 15 kg. * Participants must agree to follow study specific contraception requirements as per local regulations.
Exclusion criteria
* Known diagnosis of an IFN mediated autoinflammatory interferonopathy. * History of, or current diagnosis of, clinically significant non-SLE related vasculitides. * Active, severe SLE-driven renal disease with significant proteinuria. * Active severe or unstable neuropsychiatric SLE including but not limited to aseptic meningitis; cerebral vasculitis; myelopathy; demyelination syndromes (ascending, transverse, acute inflammatory demyelinating polyradiculopathy); acute confusional state; impaired level of consciousness; psychosis; acute stroke or stroke syndrome; cranial neuropathy; status epilepticus; cerebellar ataxia; and mononeuritis multiplex. * In participants ≥ 11 years of age, a history or evidence of suicidal ideation (severity of 4 \[active: method and intent, but no plan\] or 5 \[active: method, intent, and plan\]) within the past 6 months; or any suicidal behavior within the past 12 months or recurrent suicidal behavior in the lifetime of the participant based on an assessment with the Columbia suicide severity rating scale (C-SSRS). * History of, or current diagnosis of, catastrophic antiphospholipid syndrome (APS). * History of recurrent or opportunistic infection requiring hospitalization and intravenous (IV) antibiotics. * Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection, or a positive result for human immunodeficiency virus (HIV) infection. * Active hepatitis B and C infection. * Any active or recent herpes zoster (HZ) infection that has not completely resolved within 12 weeks prior to study entry or that emerges between screening and Day 1. * Any history of severe or recurrent HZ, including non-cutaneous HZ, herpes encephalitis, ophthalmic herpes, or 2 or more prior HZ episodes. * Any cytomegalovirus (CMV) or Epstein Barr virus (EBV) infection that has not completely resolved. * History of cancer. * Prior receipt of anifrolumab. * Prior treatment with directly acting cytotoxic B-cell depleting therapeutics. * A known history of allergy or reaction to any component of the study intervention formulation or history of anaphylaxis to any human gamma globulin therapy, human proteins, or monoclonal antibodies (mAbs).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed serum (peak) concentration (Cmax) | Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11 | To characterize PK (Cmax) of anifrolumab in pediatric participants with SLE following SC administration. |
| Area under the serum concentration-time curve (AUC) | Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11 | To characterize PK (AUC) of anifrolumab in pediatric participants with SLE following SC administration. |
| Time to maximum plasma concentration (tmax) | Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11 | To characterize PK (tmax) of anifrolumab in pediatric participants with SLE following SC administration. |
| Apparent total body clearance of drug from plasma (CL/F) | Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11 | To characterize PK (CL/F) of anifrolumab in pediatric participants with SLE following SC administration. |
| Trough drug concentration at steady state (Ctrough,ss) | At Week 12 | To characterize PK (Ctrough,ss) of anifrolumab in pediatric participants with SLE following SC administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Suppression of type I IFN 21-gene signature | At Week 12 and 52 | To characterize PD of anifrolumab in pediatric participants with SLE following SC administration. |
| Change from baseline in anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies | At Week 12 and 52 | To characterize PD of anifrolumab in pediatric participants with SLE following SC administration. |
| Change from baseline in complement component 3 (C3) levels | At Week 12 and 52 | To characterize PD of anifrolumab in pediatric participants with SLE following SC administration. |
| Change from baseline in complement component 4 (C4) levels | At Week 12 and 52 | To characterize PD of anifrolumab in pediatric participants with SLE following SC administration. |
| Change from baseline in total hemolytic complement (CH50) levels | At Week 12 and 52 | To characterize PD of anifrolumab in pediatric participants with SLE following SC administration. |
| Number and percentage of participants who develop anti drug antibody (ADA) against anifrolumab | From Day 1 to Week 52 | To evaluate the immunogenicity of anifrolumab in pediatric participants with SLE following SC administration. |
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed