An Efficacy and Safety Study of Intravenous Anifrolumab to Treat Systemic Lupus Erythematosus in Pediatric Participants (SLE)

A Phase III, Randomized, Double-blind, Parallel-group, Placebo Controlled Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of IV Anifrolumab in Pediatric Participants 5 to < 18 Years of Age With Moderate to Severe Active Systemic Lupus Erythematosus (SLE) While on Background Standard of Care Therapy

A Study to evaluate the PK, PD, efficacy, and safety of Anifrolumab in children with moderate to severe active SLE

Study Overview

• Status: Not yet recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Biological: Anifrolumab; Drug: Placebo

Detailed Description

This study aims to characterize the pharmacokinetics, pharmacodynamics, efficacy, and safety of Anifrolumab solution for infusion compared with placebo solution for infusion in pediatric participants with severe active systemic lupus erythematosus who are on background standard of care therapy.

The study duration for a participant will be approximately 120 weeks, which includes:

• Screening period of up to 30 days.
• Part A consists of a four-week, double-blind, placebo-controlled, randomised, pharmacokinetic period.
• Part B is a double-blind, placebo-controlled, randomised, safety/efficacy period lasting 48 weeks (for rollover participants from Part A) or 52 weeks (for de novo participants).
• Part C is a 52-week open-label extension period.
• Part D is a 12-week, safety follow-up period.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participant's parent/caregiver/legally authorized representative and participant (if required per local country regulation) capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Informed assent is to be provided by the participant per local country regulation.
• Diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria.
• Participant should meet all of following tuberculosis (TB) criteria:

A. No signs or symptoms of active TB B. No medical history or past physical examinations suggestive of active TB C. No recent contact with a person with active TB or if there has been such contact, referral to a TB specialist for evaluation and initiation of treatment for latent TB, if warranted, prior to the first administration of study intervention in accordance with local SoC D. No history of latent TB without documented completion of treatment prior to initial screening visit

• Female participants of childbearing potential must have a negative pregnancy test at Screening.
• Female participants of childbearing and non-childbearing potential and male participants must adhere to the contraception methods.
• At screening, negative SARS-CoV-2 RT-PCR or antigen test result and no known or suspected COVID-19 infection or exposure between screening and randomization visits.

Exclusion Criteria:

• Known diagnosis of a monogenic form of SLE.
• History of, or current diagnosis of, clinically significant non-SLE-related vasculitides.
• History or evidence of suicidal ideation.
• History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to signing the ICF.
• Any positive result on Screening for human immunodeficiency virus.
• Active hepatitis B surface antigen OR hepatitis B core antibody (HBcAb), hepatitis C virus (HCV) antibody and detectable HCV ribonucleic acid (RNA) or any severe case of Herpes Zoster infection.
• Any clinical cytomegalovirus or Epstein-Barr virus infection that has not completely resolved within 12 weeks prior to signing the ICF.
• History of severe COVID-19 infection requiring hospitalization, intensive care unit care, or assisted ventilation or any prior COVID-19 infection with unresolved sequelae. Any mild/asymptomatic COVID-19 infection (laboratory confirmed or suspected based on clinical symptoms).
• Prior use of Anifrolumab.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anifrolumab; Randomized participants will receive a single dose of Anifrolumab via IV infusion every 4 weeks	Biological: Anifrolumab; Participants will receive a single dose of Anifrolumab via IV infusion.; Other Names: (MEDI-546)
Placebo Comparator: Placebo; Randomized participants will receive matching placebo via IV infusion	Drug: Placebo; Participants will receive matching placebo via IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A - Maximum observed serum (peak) drug concentration (Cmax)	The PK will be characterised and the dose of Anifrolumab will be defined in pediatric participants with moderate to severely active SLE.	Up to Day 29
Part A - Area under the serum concentration curve (AUC)	The PK will be characterised and the dose of Anifrolumab will be defined in pediatric participants with moderate to severe active SLE.	Up to Day 29
Part A - Minimum observed serum concentration (Cmin)	Evaluation of Cmin following single dose or after dose adjustment of IV Anifrolumab or matching placebo will be done in pediatric participants with moderate to severely active SLE.	Up to Day 29
Part A - Maximum observed serum (peak) concentration at steady-state (Css, max)	Evaluation of Css, max following single dose or after dose adjustment of IV Anifrolumab or matching placebo will be done in pediatric participants with moderate to severely active SLE.	Up to Day 29
Part A - Area under the serum concentration-time curve at steady-state (AUCss)	Evaluation of AUCss following single dose or after dose adjustment of IV Anifrolumab or matching placebo will be done in pediatric participants with moderate to severely active SLE.	Up to Day 29
Part A - Average serum concentration at steady-state (Css, avg)	Evaluation of Css, avg following single dose or after dose adjustment of IV Anifrolumab or matching placebo will be done in pediatric participants with moderate to severely active SLE.	Up to Day 29
Part B - Number of participants who are British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) responders (yes/no)	BICLA response is defined as: Reduction of all baseline British Isles Lupus Assessment Group BILAG-2004 A to B/C/D and B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by ≥ 1 new BILAG-2004 A or ≥ 2 new BILAG- 2004 B.; No worsening from baseline in SLEDAI-2K, defined as an increase from baseline of > 0 points.; No worsening from baseline in participant's lupus disease activity, defined by an increase ≥ 0.30 points on a PGA 3-point visual analogue scale (VAS).	At Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part B - Number of participants who are Systemic Lupus Erythematosus Responder Index of ≥ 4 SRI(4) responders (yes/no)	SRI-4 response is defined as: ≥ 4-point reduction from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score.; No new organ systems affected as defined by ≥ 1 new BILAG-2004 A or ≥ 2 new BILAG-2004 B items compared to baseline.; No worsening from baseline in participant's lupus disease activity, defined by an increase ≥ 0.30 points on a PGA 3-point VAS.	At Week 52
Part B - Time to first flare in pediatric participants with moderate to severe active SLE	Time to first flare, where flare is defined as either ≥ 1 new BILAG-2004 A, or ≥ 2 new BILAG-2004 B items compared with the previous visit.	Through Week 52
Part - B Change from baseline through Week 52 in Anifrolumab serum concentration	The PK of Anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.	Baseline, Week 52
Part - B Change from baseline through Week 52 in antidrug antibody (ADA)	The immunogenicity of Anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.	Baseline, Week 52
Part - B Change from baseline through Week 52 in anti-dsDNA antibodies	The PD of Anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.	Baseline, Week 52
Part - B Change from baseline through Week 52 in complement components and CH50	The PD of Anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.	Baseline, Week 52
Number of participants who are Pediatric Rheumatology International Trials Organization/American College of Rheumatology (PRINTO/ACR) childhood-onset systemic lupus erythematosus (cSLE) responders (yes/no)	PRINTO/ACR cSLE responders are defined as participants with at least 50% improvement in 2 of 5 core set outcome measures and no more than one of the remaining worsening more than 30%, where the core set measures are: ParentGA 21-circle VAS; PGA 3-point VAS; SLEDAI-2K; PedsQL Generic Core (Physical Functioning Domain); Proteinuria	At Week 52
Part B - The mean percentage reduction from Baseline through Week 52 in oral corticosteroid(s) (OCS) background dose	The efficacy of Anifrolumab vs placebo on OCS background dose in pediatric participants with moderate to severe active SLE will be characterized.	Baseline, Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
All parts - Number of participants reporting suicidal ideation and/or suicidal behavior as per Columbia Suicide Severity Rating Scale (C-SSRS)	The safety and tolerability of Anifrolumab in pediatric participants with moderate to severe active SLE will be assessed.	From Week 0 until the follow-up visit (12 weeks post-last dose)
All parts - Number of participants with adverse events	The safety and tolerability of Anifrolumab in pediatric participants with moderate to severe active SLE will be assessed.	From Week 0 until the follow-up visit (12 weeks post-last dose)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Anticipated): June 21, 2023
• Primary Completion (Anticipated): October 9, 2029
• Study Completion (Anticipated): October 9, 2029

Study Registration Dates

• First Submitted: April 18, 2023
• First Submitted That Met QC Criteria: April 18, 2023
• First Posted (Actual): April 28, 2023

Study Record Updates

• Last Update Posted (Actual): April 28, 2023
• Last Update Submitted That Met QC Criteria: April 18, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: SLE; Systemic Lupus Erythematosus; Monoclonal Antibody; Intravenous; Standard of care therapy; Anifrolumab; Pediatric participants; Parallel-group treatment
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: D3461C00030

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. 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 Pharma Data Sharing Principles. For details of our timelines, please refer 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 de-identified individual patientlevel data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at:

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

• 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: No