A Study to Investigate Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Anifrolumab in Pediatric Participants 5 to < 18 Years of Age With Systemic Lupus Erythematosus

Official title

A Multicenter, Open-Label, Phase II Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Anifrolumab in Pediatric Participants 5 to < 18 Years of Age With Systemic Lupus Erythematosus

Overview

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 product Anifrolumab + APFS
  Anifrolumab will be administered as a SC injection using an APFS.

Primary outcome measures

• Maximum observed serum (peak) concentration (Cmax) [Time frame: Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11]
• Area under the serum concentration-time curve (AUC) [Time frame: Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11]
• Time to maximum plasma concentration (tmax) [Time frame: Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11]
• Apparent total body clearance of drug from plasma (CL/F) [Time frame: Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11]
• Trough drug concentration at steady state (Ctrough,ss) [Time frame: At Week 12]

Secondary outcome measures (6)

• Suppression of type I IFN 21-gene signature [Time frame: At Week 12 and 52]
• Change from baseline in anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies [Time frame: At Week 12 and 52]
• Change from baseline in complement component 3 (C3) levels [Time frame: At Week 12 and 52]
• Change from baseline in complement component 4 (C4) levels [Time frame: At Week 12 and 52]
• Change from baseline in total hemolytic complement (CH50) levels [Time frame: At Week 12 and 52]
• Number and percentage of participants who develop anti drug antibody (ADA) against anifrolumab [Time frame: From Day 1 to Week 52]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07630714 · D3465C00008 · 2025-524578-41-00 · EMA/PE/0000246211

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗