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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Combination product: Anifrolumab + APFS

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.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (body weight > 40 kg); Participants with body weight > 40 kg will receive anifrolumab as an injection in APFS.	Combination product: Anifrolumab + APFS; Anifrolumab will be administered as a SC injection using an APFS.; Other Names: MEDI-546; SAPHNELO™
Experimental: Cohort 2 (body weight ≥ 15 to ≤ 40 kg); Participants with body weight ≥ 15 to ≤ 40 kg will receive anifrolumab as an injection in APFS.	Combination product: Anifrolumab + APFS; Anifrolumab will be administered as a SC injection using an APFS.; Other Names: MEDI-546; SAPHNELO™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed serum (peak) concentration (Cmax)	To characterize PK (Cmax) of anifrolumab in pediatric participants with SLE following SC administration.	Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11
Area under the serum concentration-time curve (AUC)	To characterize PK (AUC) of anifrolumab in pediatric participants with SLE following SC administration.	Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11
Time to maximum plasma concentration (tmax)	To characterize PK (tmax) of anifrolumab in pediatric participants with SLE following SC administration.	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)	To characterize PK (CL/F) of anifrolumab in pediatric participants with SLE following SC administration.	Cohort 1: From Day 1 to Day 8; Cohort 2: From Day 1 to Day 11
Trough drug concentration at steady state (Ctrough,ss)	To characterize PK (Ctrough,ss) of anifrolumab in pediatric participants with SLE following SC administration.	At Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Suppression of type I IFN 21-gene signature	To characterize PD of anifrolumab in pediatric participants with SLE following SC administration.	At Week 12 and 52
Change from baseline in anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies	To characterize PD of anifrolumab in pediatric participants with SLE following SC administration.	At Week 12 and 52
Change from baseline in complement component 3 (C3) levels	To characterize PD of anifrolumab in pediatric participants with SLE following SC administration.	At Week 12 and 52
Change from baseline in complement component 4 (C4) levels	To characterize PD of anifrolumab in pediatric participants with SLE following SC administration.	At Week 12 and 52
Change from baseline in total hemolytic complement (CH50) levels	To characterize PD of anifrolumab in pediatric participants with SLE following SC administration.	At Week 12 and 52
Number and percentage of participants who develop anti drug antibody (ADA) against anifrolumab	To evaluate the immunogenicity of anifrolumab in pediatric participants with SLE following SC administration.	From Day 1 to Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number with participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs)	To evaluate the safety and tolerability of anifrolumab in pediatric participants with SLE following SC administration.	Up to follow-up visit (12 weeks post last dose of study intervention) (approximately 64 weeks)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Estimated): July 28, 2026
• Primary Completion (Estimated): September 3, 2030
• Study Completion (Estimated): September 5, 2031

Study Registration Dates

• First Submitted: June 2, 2026
• First Submitted That Met QC Criteria: June 2, 2026
• First Posted (Actual): June 5, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Pharmacodynamics; Human immunoglobulin (Ig) G1κ monoclonal antibody (mAb) directed against subunit 1 of the type I interferon (IFN) receptor; Accessorized pre-filled syringe
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Mycobacterium Infections, Nontuberculous; anifrolumab
• Other Study ID Numbers: D3465C00008; 2025-524578-41-00 (Ctis); EMA/PE/0000246211 (Other Identifier: Pediatric investigation plan [PIP])

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes