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 While on Background Standard of Care Therapy

Overview

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

• Biological Anifrolumab
  Participants will receive anifrolumab via IV infusion.
• Drug Placebo
  Participants will receive matching placebo via IV infusion

Primary outcome measures

• Part A- Anifrolumab serum concentration [Time frame: Pre-dose Day 29]
• Part A - Maximum observed serum (peak) drug concentration (Cmax) [Time frame: Up to Day 29]
• Part A - Area under the serum concentration curve (AUC) [Time frame: Up to Day 29]
• Part A - Minimum observed serum concentration (Cmin) [Time frame: Up to Day 29]
• Part B - Number of participants who are British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) responders (yes/no) [Time frame: At Week 52]

Secondary outcome measures (11)

• Part B - Number of participants who are Systemic Lupus Erythematosus Responder Index of ≥ 4 SRI(4) responders (yes/no) [Time frame: At Week 52]
• Part B - Time to first flare [Time frame: Through Week 52]
• Part B - Anifrolumab serum concentration [Time frame: Pre-dose Week 12, Pre-dose Week 24, Pre-dose Week 52]
• Part - B Change from baseline through Week 52 in antidrug antibody (ADA) [Time frame: Up to Week 52]
• Part - B Change from baseline in anti-double stranded deoxyribonucleic acid antibodies [Time frame: At Week 12 and Week 52]
• Part - B Change from baseline in total hemolytic complement (CH50) [Time frame: At Week 12 and Week 52]
• Part - B Change from baseline in complement component (C3) [Time frame: At Week 12 and Week 52]
• Part - B Change from baseline in complement component (C4) [Time frame: At Week 12 and Week 52]
• 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) [Time frame: At Week 52]
• Part B - The mean percentage reduction from Baseline through Week 52 in oral corticosteroid(s) (OCS) background dose [Time frame: At Week 52]
• Part B - Change from baseline through Week 52 in type I interferon (IFN) 21-gene signature [Time frame: At Week 52]

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 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 22 centers

• Research Site — Phoenix
• Research Site — Los Angeles
• Research Site — Washington D.C.
• Research Site — Chicago
• Research Site — Chicago
• Research Site — New Orleans
• Research Site — Bethesda
• Research Site — Saint Paul
• … and 14 more centers

China · 10 centers

• Research Site — Beijing
• Research Site — Beijing
• Research Site — Beijing
• Research Site — Changchun
• Research Site — Changsha
• Research Site — Nanjing
• Research Site — Shanghai
• Research Site — Suzhou
• … and 2 more centers

Japan · 10 centers

• Research Site — Bunkyō City
• Research Site — Bunkyō City
• Research Site — Chiba
• Research Site — Fuchu-shi
• Research Site — Kawasaki-shi
• Research Site — Kobe
• Research Site — Obu-shi
• Research Site — Shinjuku-ku
• … and 2 more centers

Spain · 7 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 7 centers

Center list to be confirmed — check the primary protocol.

Brazil · 5 centers

• Research Site — Belo Horizonte
• Research Site — Porto Alegre
• Research Site — Ribeirão Preto
• Research Site — São Paulo
• Research Site — São Paulo

France · 5 centers

• Research Site — Bordeaux
• Research Site — Bron
• Research Site — Le Kremlin-Bicêtre
• Research Site — Lille
• Research Site — Toulouse

Italy · 5 centers

• Research Site — Genova
• Research Site — Milan
• Research Site — Milan
• Research Site — Padova
• Research Site — Roma

Mexico · 5 centers

• Research Site — Atizapán de Zaragoza
• Research Site — Guadalajara
• Research Site — Mérida
• Research Site — México
• Research Site — Monterrey

Argentina · 4 centers

• Research Site — Buenos Aires
• Research Site — Córdoba
• Research Site — Rosario
• Research Site — San Miguel de Tucumán

Turkey (Türkiye) · 4 centers

Center list to be confirmed — check the primary protocol.

Canada · 3 centers

• Research Site — Calgary
• Research Site — Vancouver
• Research Site — Toronto

Germany · 3 centers

• Research Site — Berlin
• Research Site — Freiburg im Breisgau
• Research Site — Sankt Augustin

Poland · 3 centers

• Research Site — Lodź
• Research Site — Warsaw
• Research Site — Wroclaw

Portugal · 3 centers

• Research Site — Lisbon
• Research Site — Lisbon
• Research Site — Porto

Colombia · 2 centers

• Research Site — Barranquilla
• Research Site — Medellín

South Africa · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT05835310 · D3461C00030 · 2022-502289-25-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗