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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Biological: Anifrolumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Lupus Erythematosus, SLE, Monoclonal Antibody, Anifrolumab, Parallel-group treatment, Pediatric participants, Standard of care therapy, Intravenous