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).
RACEMATE is a randomised double-blind placebo-controlled experimental medicine study designed to explore both the efficacy and mechanism of action of tezepelumab (210 milligram \[mg\] administered subcutaneously \[SC\] every 4 weeks) compared with placebo over a 24-week study treatment period in subjects with active (non-severe) Eosinophilic Granulomatosis with Polyangiitis (EGPA) receiving standard of care therapy including background corticosteroid therapy with or without immunomodulatory therapy. This study will take place across 16 centres in the United Kingdom. Corticosteroid dose will be tapered during the treatment period in accordance with standard of care. The key outcome of this study focuses on evaluation of clinical remission, defined as a Birmingham Vasculitis Activity Score (BVAS) version 3 of 0 and receipt of prednisolone ≤ 4mg daily and no receipt of oral corticosteroids above baseline during the treatment period. Secondary outcomes will include reduction in disease flare, improvement in scores for asthma control, sino-nasal disease and spirometry amongst others.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
66
Tezepelumab subcutaneous injection
Placebo subcutaneous injection
Aberdeen Royal Infirmary - NHS Grampian
Aberdeen, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
Proportion of participants who are in remission at week 24
The proportion of patients who achieve remission at week 24 (defined as a Birmingham Vasculitis Activity 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). BVAS is a validated tool for assessment of disease activity in patients with vasculitis with potential scores ranging from 0-63, with higher scores indicating worse disease activity.
Time frame: Week 24
Time to first EGPA flare
EGPA flare was defined as worsening or recurrence of active disease since the last visit characterised by active vasculitis (BVAS \>0) or active asthma symptoms and/or signs with a corresponding worsening in Asthma Control Questionnaire-6 (ACQ-6) score or active nasal and/or sinus disease, with a corresponding worsening in at least one of the sino-nasal symptom questions warranting: (i) rescue use of prednisolone/equivalent systemic steroid for 3 or more days OR an increase in background prednisolone/equivalent systemic steroid dose by at least 5 mg daily of prednisolone equivalents for at least three days OR (ii) an increased dose or addition of immunosuppressive therapy; OR (iii) hospitalization related to EGPA worsening. The number of participants with at least one EGPA flare during the planned study treatment period are presented.
Time frame: Up to Week 24
Total accrued duration of remission
Total accrued weeks of remission defined as defined as a Birmingham Vasculitis Activity Score (BVAS) - version 3, score of 0 with mOCS dose of prednisolone/prednisolone ≤ 4mg/day and BVAS of 0.
Time frame: Up to Week 24
Proportion of participants that demonstrate sustained remission
The proportion of patients that demonstrate sustained remission at both weeks 20 and 24 (defined as a BVAS version 3 score of 0 and receipt of prednisolone of ≤ 4 mg daily and no receipt of oral steroids above baseline dose between weeks 16 and 24)
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Cambridge, United Kingdom
University Hospitals of Leicester NHS Trust
Leicester, United Kingdom
Liverpool University Hospitals NHS Foundation Trust
Liverpool, United Kingdom
Barts Health NHS Trust
London, United Kingdom
Royal Free London NHS Trust
London, United Kingdom
Guy's Hospital - Guy's and St Thomas' NHS Foundation Trust
London, United Kingdom
Royal Brompton Hospital - Guy's and St Thomas' NHS Foundation Trust
London, United Kingdom
Imperial College Healthcare NHS Trust
London, United Kingdom
...and 3 more locations
Time frame: Up to Week 24
Proportion of participants that tapered mOCS by at least 2.5 mg/day
Proportion of patients that tapered their maintenance oral corticosteroids (mOCS) by at least 2.5 mg/day of prednisolone equivalent during the OCS tapering period, who remained in remission
Time frame: Up to Week 24
Change in SinoNasal Outcome Test-22 (SNOT-22)
Change from baseline (week 0) to weeks 12 \& 24 in the SinoNasal Outcome Test-22 questionnaire score (SNOT-22). SNOT-22 is a validated assessment of the burden of chronic rhinosinusitis with potential scores ranging from 0-110, with higher scores indicating a worse impact on health-related quality of life.
Time frame: Between Week 0 and/or Week 12 and Week 24
Change in European Quality of Life 5 Dimensions 5 Level (EuroQoL-5D-5L)
Change from baseline (week 0) to week 24 in the European Quality of Life 5 Dimensions 5 Level (EuroQoL-5D-5L) questionnaire score. The EuroQoL-5D-5L is a validated standardised descriptive measure of health-related quality of life with potential scores ranging from "no problems" to "extreme problems" in all domains. The questionnaire also asks the participant to indicate their overall health that day on a scale of 0-100, with lower scores indicating worse health.
Time frame: Up to Week 24
Change in Juniper 6-item Asthma Control Questionnaire (ACQ-6)
Change from baseline to week 12 and 24 in Juniper 6-item Asthma Control Questionnaire (ACQ-6) score. The ACQ-6 is a validated assessment of asthma symptom control, with potential scores ranging from 0-6, with higher scores indicating worse asthma symptom control.
Time frame: Between Week 0 and/or Week 12 and Week 24
Change in blood eosinophil level
Change from baseline (week 0) to week 12 and 24 in blood eosinophil level
Time frame: Between Week 0 and/or Week 12 and Week 24
Change in spirometry
Change from baseline (week 0) to weeks 12 and 24 in pre-bronchodilator FEV1% predicted and FEV1/FVC ratio.
Time frame: Between Week 0 and/or Week 12 and Week 24
Change in FeNO
Change from baseline (week 0) to weeks 12 and 24 in Fractional Exhaled Nitric Oxide level (FeNO).
Time frame: Between Week 0 and/or Week 12 and Week 24
Change in eGFR
Change from baseline (week 0) to weeks 12 and 24 in estimated glomerular filtration rate (eGFR).
Time frame: Between Week 0 and/or Week 12 and Week 24