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

Systemic Lupus Erythematosus Clinical Trial

— SLE  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05835310
• Other study ID #: D3461C00030
• Status: Recruiting
• Phase: Phase 3
• Start date: March 14, 2024
• Est. completion date: January 15, 2030

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: January 15, 2030
• Est. primary completion date: July 25, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Biological:
• Anifrolumab
Participants will receive a single dose of Anifrolumab via IV infusion.

Drug:
• Placebo
Participants will receive matching placebo via IV infusion

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Córdoba
Argentina	Research Site	Rosario
Brazil	Research Site	Botucatu
Brazil	Research Site	Curitiba
Brazil	Research Site	Ribeirão Preto
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Shanghai
China	Research Site	Suzhou
China	Research Site	Wenzhou
China	Research Site	Zhengzhou
Colombia	Research Site	Barranquilla
Colombia	Research Site	Medellin
France	Research Site	Bordeaux Cedex
France	Research Site	Bron
France	Research Site	Le Kremlin Bicetre
France	Research Site	LILLE Cedex
France	Research Site	Toulouse
Germany	Research Site	Berlin
Germany	Research Site	Freiburg
Germany	Research Site	Sankt Augustin
Italy	Research Site	Genova
Italy	Research Site	Milano
Italy	Research Site	Padova
Italy	Research Site	Roma
Mexico	Research Site	Guadalajara
Mexico	Research Site	Merida
Mexico	Research Site	Mexico
Mexico	Research Site	Monterrey
Poland	Research Site	Lodz
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Porto
South Africa	Research Site	Cape Town
Spain	Research Site	Esplugues de Llobregat
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Valencia
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Kayseri
Turkey	Research Site	Umraniye
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Southampton
United States	Research Site	Bethesda	Maryland
United States	Research Site	Bronx	New York
United States	Research Site	Chicago	Illinois
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	El Paso	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Los Angeles	California
United States	Research Site	New Hyde Park	New York
United States	Research Site	New York	New York
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Portland	Oregon
United States	Research Site	Saint Paul	Minnesota
United States	Research Site	Salt Lake City	Utah
United States	Research Site	Valhalla	New York
United States	Research Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  China,  Colombia,  France,  Germany,  Italy,  Mexico,  Poland,  Portugal,  South Africa,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	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)
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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