Systemic Lupus Erythematosus
Conditions
Keywords
Systemic Lupus Erythematosus, SLE, Monoclonal Antibody, Anifrolumab, Parallel-group treatment, Pediatric participants, Standard of care therapy, Intravenous
Brief summary
A Study to Evaluate the Pharmacokinetics (PK), Pharmacodynamics (PD), Efficacy, and Safety of Anifrolumab in Children with Moderate to Severe Active Systemic Lupus Erythematosus (SLE)
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 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.
Interventions
BIOLOGICALAnifrolumab
Participants will receive anifrolumab via IV infusion.
DRUGPlacebo
Participants will receive matching placebo via IV infusion
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
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 for at least 3 months prior to signing the ICF. * At Screening, participant must have moderate to severe active SLE disease, as adjudicated by the Central Adjudication Committee, defined as: (a) SLEDAI-2K activity of: (i) ≥ 6 points with at least 4 points (≥ 4 points) coming from the following clinical components ('Clinical' SLEDAI-2K score): arthritis, myositis, rash, alopecia, mucosal ulcers, pleurisy, pericarditis, or vasculitis and excluding points attributed to a fever, SLE headache, and organic brain syndrome (ii) Clinical SLEDAI score of ≥ 4 points verified at Day 1 (b) BILAG-2004 activity of: (i) ≥ 1 BILAG A score; or (ii) ≥ 2 BILAG B scores (c) PGA score ≥ 1.0 on a 0 to 3 VAS * 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 serum pregnancy test at screening and negative urine pregnancy test at randomization. * Female participants of childbearing and male participants must adhere to the contraception methods.
Exclusion criteria
* Known diagnosis of an IFN-mediated autoinflammatory interferonopathy. * History of, or current diagnosis of, clinically significant non-SLE-related vasculitides. * In participants aged 11 years and above: 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 active or recent 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. * Prior treatment with directly acting cytotoxic B-cell depleting therapeutics (eg, rituximab) \< 26 weeks prior to ICF signature. * Blood transfusion or receipt of blood products except albumin within 4 weeks prior to signing the ICF.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A- Anifrolumab serum concentration | Pre-dose Day 29 | The serum concentration will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severely active SLE. |
| Part A - Maximum observed serum (peak) drug concentration (Cmax) | Up to Day 29 | The serum PK will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severely active SLE. |
| Part A - Area under the serum concentration curve (AUC) | Up to Day 29 | The serum PK will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severe active SLE. |
| Part A - Minimum observed serum concentration (Cmin) | Up to Day 29 | The serum PK will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severe active SLE. |
| Part B - Number of participants who are British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) responders (yes/no) | At Week 52 | 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 Systemic Lupus Erythematosus Disease Activity Index 2000 (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 Physician's Global Assessment (PGA) 3-point visual analogue scale (VAS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B - Number of participants who are Systemic Lupus Erythematosus Responder Index of ≥ 4 SRI(4) responders (yes/no) | At Week 52 | SRI-4 response is defined as: * ≥ 4-point reduction from baseline in 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. |
| Part B - Time to first flare | Through Week 52 | 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. |
| Part B - Anifrolumab serum concentration | Pre-dose Week 12, Pre-dose Week 24, Pre-dose Week 52 | The PK of anifrolumab in pediatric participants with moderate to severe active SLE will be characterized. |
| Part - B Change from baseline through Week 52 in antidrug antibody (ADA) | Up to Week 52 | The immunogenicity of anifrolumab in pediatric participants with moderate to severe active SLE will be characterized. |
| Part - B Change from baseline in anti-double stranded deoxyribonucleic acid antibodies | At Week 12 and Week 52 | The PD of anifrolumab in pediatric participants with moderate to severe active SLE will be characterized. |
| Part - B Change from baseline in total hemolytic complement (CH50) | At Week 12 and Week 52 | The PD of anifrolumab in pediatric participants with moderate to severe active SLE will be characterized. |
| Part - B Change from baseline in complement component (C3) | At Week 12 and Week 52 | The PD of anifrolumab in pediatric participants with moderate to severe active SLE will be characterized. |
| Part - B Change from baseline in complement component (C4) | At Week 12 and Week 52 | The PD of anifrolumab in pediatric participants with moderate to severe active SLE will be characterized. |
| 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) | At Week 52 | 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 |
| Part B - The mean percentage reduction from Baseline through Week 52 in oral corticosteroid(s) (OCS) background dose | At Week 52 | The efficacy of anifrolumab vs placebo on OCS background dose in pediatric participants with moderate to severe active SLE will be characterized. |
| Part B - Change from baseline through Week 52 in type I interferon (IFN) 21-gene signature | At Week 52 | Type 1 IFN 21 gene signatures in pediatric patients with moderate to active SLE will be characterized. |
Countries
Argentina, Brazil, Canada, China, Colombia, France, Germany, Italy, Japan, Mexico, Poland, Portugal, South Africa, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed