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

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 116 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 safety follow-up period. One safety visit at 12 weeks post last dose.

Primary Outcome Measures

1. Part A- Anifrolumab serum concentration
   The serum concentration will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severely active SLE.
2. Part A - Maximum observed serum (peak) drug concentration (Cmax)
   The serum PK will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severely active SLE.
3. Part A - Area under the serum concentration curve (AUC)
   The serum PK will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severe active SLE.
4. Part A - Minimum observed serum concentration (Cmin)
   The serum PK will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severe active SLE.
5. 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).

Secondary Outcome Measures

1. 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.
2. Part B - Time to first flare
   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.
3. Part B - Anifrolumab serum concentration
   The PK of anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.
4. 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.
5. Part - B Change from baseline in anti-double stranded deoxyribonucleic acid antibodies
   The PD of anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.
6. Part - B Change from baseline in total hemolytic complement (CH50)
   The PD of anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.
7. Part - B Change from baseline in complement component (C3)
   The PD of anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.
8. Part - B Change from baseline in complement component (C4)
   The PD of anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.
9. 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 from baseline in any 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
10. 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.
11. Part B - Change from baseline through Week 52 in type I interferon (IFN) 21-gene signature
    Type 1 IFN 21 gene signatures in pediatric patients with moderate to active SLE will be characterized.