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

Brief Summary
A Study to evaluate the PK, PD, efficacy, and safety of Anifrolumab in children with moderate to severe active SLE
Brief Title
An Efficacy and Safety Study of Intravenous Anifrolumab to Treat Systemic Lupus Erythematosus in Pediatric Participants
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, single-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.
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-877-240-9479
Central Contact Email
information.center@astrazeneca.com
Completion Date
Completion Date Type
Estimated
Conditions
Systemic Lupus Erythematosus
Eligibility Criteria
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 6 months prior to signing the ICF.
* 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 rapid antigen test result and no known or suspected COVID-19 infection or exposure between screening and randomization visits.

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 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.
* 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.
Inclusion Criteria
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 6 months prior to signing the ICF.
* 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 rapid antigen test result and no known or suspected COVID-19 infection or exposure between screening and randomization visits.

Gender
All
Gender Based
false
Keywords
Systemic Lupus Erythematosus
SLE
Monoclonal Antibody
Anifrolumab
Parallel-group treatment
Pediatric participants
Standard of care therapy
Intravenous
Healthy Volunteers
No
Last Update Submit Date
Maximum Age
17 Years
Minimum Age
5 Years
NCT Id
NCT05835310
Org Class
Industry
Org Full Name
AstraZeneca
Org Study Id
D3461C00030
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
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
Primary Outcomes
Outcome Description
The PK will be characterised and the dose of Anifrolumab will be defined in pediatric participants with moderate to severely active SLE.
Outcome Measure
Part A - Maximum observed serum (peak) drug concentration (Cmax)
Outcome Time Frame
Up to Day 29
Outcome Description
The PK will be characterised and the dose of Anifrolumab will be defined in pediatric participants with moderate to severe active SLE.
Outcome Measure
Part A - Area under the serum concentration curve (AUC)
Outcome Time Frame
Up to Day 29
Outcome Description
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.
Outcome Measure
Part A - Minimum observed serum concentration (Cmin)
Outcome Time Frame
Up to Day 29
Outcome Description
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.
Outcome Measure
Part A - Maximum observed serum (peak) concentration at steady-state (Css, max)
Outcome Time Frame
Up to Day 29
Outcome Description
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.
Outcome Measure
Part A - Area under the serum concentration-time curve at steady-state (AUCss)
Outcome Time Frame
Up to Day 29
Outcome Description
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.
Outcome Measure
Part A - Average serum concentration at steady-state (Css, avg)
Outcome Time Frame
Up to Day 29
Outcome Description
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).
Outcome Measure
Part B - Number of participants who are British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) responders (yes/no)
Outcome Time Frame
At Week 52
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
At Week 52
Outcome Measure
Part B - Number of participants who are Systemic Lupus Erythematosus Responder Index of ≥ 4 SRI(4) responders (yes/no)
Outcome Description
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.
Outcome Time Frame
Through Week 52
Outcome Measure
Part B - Time to first flare in pediatric participants with moderate to severe active SLE
Outcome Description
The PK of Anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Part - B Change from baseline through Week 52 in Anifrolumab serum concentration
Outcome Description
The immunogenicity of Anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Part - B Change from baseline through Week 52 in antidrug antibody (ADA)
Outcome Description
The PD of Anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Part - B Change from baseline through Week 52 in anti-dsDNA antibodies
Outcome Description
The PD of Anifrolumab in pediatric participants with moderate to severe active SLE will be characterized.
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Part - B Change from baseline through Week 52 in complement components and CH50
Outcome Description
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
Outcome Time Frame
At Week 52
Outcome Measure
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)
Outcome Description
The efficacy of Anifrolumab vs placebo on OCS background dose in pediatric participants with moderate to severe active SLE will be characterized.
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Part B - The mean percentage reduction from Baseline through Week 52 in oral corticosteroid(s) (OCS) background dose
Outcome Description
Type 1 IFN 21 gene signatures in pediatric patients with moderate to active SLE will be characterized.
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Part B - Change from baseline through Week 52 in type I interferon (IFN) 21-gene signature
Start Date
Start Date Type
Actual
Status Verified Date
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
17
Minimum Age Number (converted to Years and rounded down)
5
Investigators
Investigator Type
Principal Investigator
Investigator Name
Dawn Wahezi
Investigator Email
dwahezi@montefiore.org
Investigator Phone
718-696-2405