A RAndomised Placebo Controlled Trial - to Explore the Efficacy and Mechanism of Action of Tezepelumab in EGPA- RACE-MATE

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Imperial College London Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2025-05-02

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

AstraZeneca

External identifiers

EU CT number

2024-514794-22-01

ClinicalTrials.gov

NCT06230354

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

RACEMATE is a phase 2b, multicentre, randomised, double-blinded, placebo-controlled study designed to explore the efficacy and mechanism of action of Tezepelumab in adults with eosinophilic granulomatosis with polyangiitis (EGPA). To compare the proportion of patients with EGPA that maintain remission over 24 weeks, in a randomised, double blind, multi-centre, placebo-controlled trial - comparing Tezepelumab to placebo.

Secondary objectives 1

1. To evaluate the impact of Tezepelumab relative to placebo on a range of secondary clinical and biomarker endpoints capturing airways disease and vasculitis activity.

Conditions and MedDRA coding

Eosinophilic granulomatosis with polyangiitis (EGPA)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Health Research Authority, Medicines And Healthcare Products Regulatory Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Minimum Age: 18 Years Maximum Age: 75 Years Sex: All Gender Based: Accepts Healthy Volunteers: No Criteria: Inclusion Criteria: Capable of providing written informed consent Eosinophilic granulomatosis with polyangiitis is defined as a history of asthma, a blood eosinophil level of 10% or an absolute eosinophil count of more than 1.0 x10^9/L, and the presence of two or more criteria: - Histopathological evidence of eosinophilic vasculitis - Perivascular eosinophilic infiltration, or eosinophil-rich granulomatous inflammation - Neuropathy - Pulmonary infiltrate Sino-nasal abnormality Cardiomyopathy Glomerulonephritis Alveolar haemorrhage Palpable purpura Anti-neutrophil cytoplasmic antibody [ANCA] positivity History of one or more flares of EGPA in 24 months prior to screening. EGPA flares will be defined as worsening or persistence of active disease characterised by: - Active vasculitis (BVAS >0); OR - An asthma exacerbation/asthma worsening OR - Active nasal and/or sinus disease Warranting: - Rescue use of prednisolone for 3 or more days OR an increase in background prednisolone dose by at least 5 mg daily for at least three days OR - An increased dose or addition of immunosuppressive therapy; OR Hospitalisation related to EGPA worsening Blood eosinophil level at screening (visit 1) of ≥ 0.2 x10^9/L (participants can be re screened once within 2 weeks if the BEC is < 0.2 x10^9/L at the initial screening assessment). n.b. This criterion is not relevant for participants taking background anti-IL-5/5R biological agents mepolizumab (MEPO) or benralizumab (BRZ) in which any baseline blood eosinophil count (BEC) permitted. Non severe EGPA according to the American College of Rheumatology 2021 definition. Non-Severe EGPA: Vasculitis without life- or organ-threatening manifestations (e.g., rhinosinusitis, asthma, mild systemic symptoms, uncomplicated cutaneous disease, mild inflammatory arthritis). 6. Stable dose of prednisolone (≥5.0 to ≤30.0 mg per day, with or without additional Immunomodulatory therapy) for at least 4 weeks before the baseline visit. 7. Immunomodulatory therapy: (i) If receiving non-biologic immunomodulatory therapy, the dosage must be stable for the 4 weeks prior to baseline visit. (ii) Patients on background anti-IL-5/5R therapy (either MEPO or BRZ) at any licensed dose for the current clinical indications of severe asthma and EGPA in the UK and Europe respectively AND have been on treatment for at least 6 months. n.b. participants on background anti-IL-5/5R therapy will be capped to no more than 50% of the total sample size.

Exclusion criteria 1

1. Diagnosis of Granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Pregnancy or unable to use a highly effective method of birth control (confirmed by the Investigator) from randomisation throughout the study duration and within 8 weeks after last dose of IMP. Active life- or organ-threatening manifestations of EGPA within 6 months prior to screening, defined as: Severe alveolar haemorrhage Rapidly progressive glomerulonephritis Severe gastrointestinal or central nervous system involvement requiring intensification of immunosuppression or surgery Severe cardiac involvement including life threatening arrhythmia, heart failure with an ejection fraction < 20% or acute myocardial infarction or active myocarditis Current active malignancy. Immunodeficiency including HIV Helminth infection within 6-months of screening that has not been treated or remains refractory to treatment. Unstable liver disease with the exception of Gilberts syndrome or asymptomatic gallstones. Use of a prohibited concurrent medication as listed below: Biologic therapy for severe asthma (except MEPO or BRZ) within 4 months or 5 half-lives (whichever is longer) prior to Visit 1 or receipt of any investigational non-biologic agent within 30 days or 5 half-lives (whichever is longest) prior to Visit 1. Biologic therapies for EGPA including Rituximab and Alemtuzumab within 6 months of visit 1. IV or SC immunoglobulin therapy within 3 months of visit 1. Oral cyclophosphamide within 6 weeks of screening or IV cyclophosphamide within 4 months of visit 1. IM or IV corticosteroids within 6 weeks of visit 1. Known adrenal insufficiency (primary or secondary), that in the opinion of the investigator and clinical care team preclude maintenance oral steroid tapering

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the proportion of patients, who achieve remission at week 24 (defined as a Birmingham Vasculitis Score (BVAS) version 3 score of 0 and receipt of prednisolone of ≤ 4mg daily and no receipt of oral steroids above baseline dose in the 4 weeks prior to week 24).

Secondary endpoints 1

1. (I) Time to first EGPA flare. (II) Total accrued weeks of remission defined as defined as a Birmingham Vasculitis Activity Score (BVAS) – version 3(11), score of 0 with mOCS dose of prednisolone/prednisolone ≤ 4mg/day and BVAS of 0.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Imperial College London Limited

Sponsor organisation

Imperial College London Limited

Address

Paddington, Norfolk Place Norfolk Place

City

London

Postcode

W2 1PG

Country

United Kingdom

Scientific contact point

Organisation

Imperial College London Limited

Contact name

Prof Salman Siddiqui

Public contact point

Organisation

Imperial College London Limited

Contact name

Prof Salman Siddiqui

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications