Clinical trial NCT05835310: An Efficacy and Safety Study of Intravenous Anifrolumab to Treat Systemic Lupus Erythematosus in Pediatric Participants
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Systemic Lupus Erythematosus
Keywords: Systemic Lupus Erythematosus
SLE
Monoclonal Antibody
Anifrolumab
Parallel-group treatment
Pediatric participants
Standard of care therapy
Intravenous
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-04-28
Enrollment: 100
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Study to evaluate the PK, PD, efficacy, and safety of Anifrolumab in children with moderate to severe active 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, 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.

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.

Primary outcomes:
measure: Part A - Maximum observed serum (peak) drug concentration (Cmax)
timeFrame: Up to Day 29
measure: Part A - Area under the serum concentration curve (AUC)
timeFrame: Up to Day 29
measure: Part A - Minimum observed serum concentration (Cmin)
timeFrame: Up to Day 29
measure: Part A - Maximum observed serum (peak) concentration at steady-state (Css, max)
timeFrame: Up to Day 29
measure: Part A - Area under the serum concentration-time curve at steady-state (AUCss)
timeFrame: Up to Day 29
measure: Part A - Average serum concentration at steady-state (Css, avg)
timeFrame: Up to Day 29
measure: Part B - Number of participants who are British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) responders (yes/no)
timeFrame: At Week 52
Secondary outcomes:
measure: Part B - Number of participants who are Systemic Lupus Erythematosus Responder Index of ≥ 4 SRI(4) responders (yes/no)
timeFrame: At Week 52
measure: Part B - Time to first flare in pediatric participants with moderate to severe active SLE
timeFrame: Through Week 52
measure: Part - B Change from baseline through Week 52 in Anifrolumab serum concentration
timeFrame: Baseline, Week 52
measure: Part - B Change from baseline through Week 52 in antidrug antibody (ADA)
timeFrame: Baseline, Week 52
measure: Part - B Change from baseline through Week 52 in anti-dsDNA antibodies
timeFrame: Baseline, Week 52
measure: Part - B Change from baseline through Week 52 in complement components and CH50
timeFrame: Baseline, Week 52
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)
timeFrame: At Week 52
measure: Part B - The mean percentage reduction from Baseline through Week 52 in oral corticosteroid(s) (OCS) background dose
timeFrame: Baseline, Week 52
measure: Part B - Change from baseline through Week 52 in type I interferon (IFN) 21-gene signature
timeFrame: Baseline, Week 52
Other outcomes:
measure: All parts - Number of participants reporting suicidal ideation and/or suicidal behavior as per Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: From Week 0 until the follow-up visit (12 weeks post-last dose)
measure: All parts - Number of participants with adverse events
timeFrame: From Week 0 until the follow-up visit (12 weeks post-last dose)
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Saint Paul
country: United States
facility: Research Site
state: Minnesota
city: Bronx
country: United States
facility: Research Site
state: New York
city: New Hyde Park
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Valhalla
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: El Paso
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Córdoba
country: Argentina
facility: Research Site
city: Rosario
country: Argentina
facility: Research Site
city: Botucatu
country: Brazil
facility: Research Site
city: Curitiba
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Ribeirão Preto
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Suzhou
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Barranquilla
country: Colombia
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Bron
country: France
facility: Research Site
city: Le Kremlin-Bicêtre
country: France
facility: Research Site
city: LILLE Cedex
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Freiburg
country: Germany
facility: Research Site
city: Sankt Augustin
country: Germany
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Chiba
country: Japan
facility: Research Site
city: Fuchu-shi
country: Japan
facility: Research Site
city: Kawasaki-shi
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
facility: Research Site
city: Obu-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Merida
country: Mexico
facility: Research Site
city: Mexico
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: Toluca
country: Mexico
facility: Research Site
city: Lodź
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Esplugues de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Kayseri
country: Turkey
facility: Research Site
city: Umraniye
country: Turkey
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Southampton
country: United Kingdom
facility: Research Site
Study officials:
References: