Randomized, Double-Blind, Placebo-Controlled Study of Tezepelumab in Adults with Eosinophilic Granulomatosis with Polyangiitis (EGPA)
- Trial ID
- 2024-514794-22-01
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to explore the **efficacy** and mechanism of action of Tezepelumab in adults with **eosinophilic granulomatosis with polyangiitis (EGPA)**. The study aims to compare the proportion of patients with EGPA who maintain remission over a 24-week period in a randomised, double-blind, multi-centre, placebo-controlled trial, comparing Tezepelumab to placebo. This is clinically relevant as maintaining remission in EGPA is crucial for improving patient outcomes and quality of life.
Secondary objectives include evaluating the impact of Tezepelumab relative to placebo on a range of secondary clinical and biomarker endpoints that capture airways disease and vasculitis activity. These evaluations are important for understanding the broader effects of Tezepelumab on disease activity and potential biomarkers associated with EGPA.
Participants
The clinical trial involves a total of **56 participants** diagnosed with **eosinophilic granulomatosis with polyangiitis (EGPA)**. The study population comprises adults aged between **18 and 75 years**, inclusive of both **male and female** subjects. Participants were selected based on specific criteria, including a history of asthma and a blood eosinophil level indicative of EGPA. The trial does not include healthy volunteers, and individuals with severe manifestations of EGPA are excluded. Participants are required to have a stable dose of prednisolone and, if applicable, a stable regimen of immunomodulatory therapy prior to the baseline visit. The trial does not involve a vulnerable population, and lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The study aims to evaluate the efficacy of Tezepelumab in maintaining remission in EGPA patients over a 24-week period.
Plans and Procedures
The clinical trial is a **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the efficacy and mechanism of action of **Tezepelumab** in adults with **eosinophilic granulomatosis with polyangiitis (EGPA)**. The trial is classified as a Phase IIb study and is expected to span a duration from January 2025 to May 2026. Participants will be randomly assigned to receive either Tezepelumab or a placebo, both administered as a **solution for injection** via **subcutaneous injection**. The primary endpoint is the proportion of patients achieving remission at week 24, defined by a Birmingham Vasculitis Score (BVAS) of 0 and a prednisolone dose of ≤4 mg daily without exceeding the baseline dose in the four weeks prior to week 24.
The study will commence with an inclusion (screening) visit to assess eligibility based on criteria such as age, medical history, and current health status. Participants must have a history of asthma, specific blood eosinophil levels, and meet additional criteria related to EGPA symptoms and treatment history. Following the screening, eligible participants will undergo a baseline visit where they will be randomized into treatment groups. Subsequent follow-up visits will occur at regular intervals to monitor the participants' health, treatment adherence, and response to the intervention. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the primary and secondary endpoints, including time to first EGPA flare and total accrued weeks of remission.
Participant involvement is expected to last up to 24 weeks, with the possibility of early termination if specific conditions arise, such as adverse reactions, non-compliance with the study protocol, or withdrawal of consent. The trial aims to maintain a stable dose of prednisolone and any immunomodulatory therapy for at least four weeks before the baseline visit. Participants on background anti-IL-5/5R therapy will be capped at no more than 50% of the total sample size. The study is not open to healthy volunteers, and all participants must provide written informed consent prior to enrollment.
Treatment
The clinical trial involves the administration of **Tezepelumab**, marketed under the name Tezspire, which is a **solution for injection** in a pre-filled syringe. The active substance, **Tezepelumab**, is a protein of other origin, specifically designed for subcutaneous injection. Each dose contains 210 mg of Tezepelumab, and the maximum daily and total dose is 210 mg. The treatment period for Tezepelumab is set at 7 days, with the administration occurring once weekly. The pharmaceutical form is a solution for injection, and the product is authorized under the marketing authorization number EU/1/22/1677/002. The product is manufactured by AstraZeneca AB and is identified by the EU medicinal product number PRD10215100.
The trial also includes a **placebo** as a comparator treatment, which is a **solution for injection** administered via subcutaneous injection. The placebo is chemically derived and is used to compare against the effects of Tezepelumab. The placebo is administered in the same manner as Tezepelumab, with a maximum daily and total dose of 210 mg, and a treatment period of 28 days. The placebo is identified by the EU medicinal product number SUB21402. The use of a placebo allows for a double-blinded, placebo-controlled study design, ensuring the efficacy and mechanism of action of Tezepelumab can be accurately assessed in patients with eosinophilic granulomatosis with polyangiitis (EGPA).
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the primary and secondary endpoints related to the treatment of **eosinophilic granulomatosis with polyangiitis (EGPA)**. The primary endpoint is the proportion of patients who achieve remission at week 24. Remission is defined as a Birmingham Vasculitis Activity Score (BVAS) version 3 score of 0, with a prednisolone dose of ≤ 4 mg daily, and no receipt of oral steroids above the baseline dose in the 4 weeks prior to week 24.
Secondary endpoints include the time to the first EGPA flare and the total accrued weeks of remission. Remission for secondary endpoints is similarly defined as a BVAS version 3 score of 0, with a maintenance oral corticosteroid (mOCS) dose of prednisolone/prednisone ≤ 4 mg/day and a BVAS of 0. These efficacy parameters will be measured and collected at specified timepoints throughout the trial, with the primary endpoint being assessed at week 24. The BVAS is a validated tool used to quantify disease activity in patients with vasculitis, ensuring a standardized approach to efficacy assessment.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Yet Recruiting | 01 Jan 2025 | 10 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
PLACEBO | Test | — | SUBCUTANEOUS INJECTION | 210 | 28 | SUB21402 |
Tezspire 210 mg solution for injection in pre-filled syringe | Test | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS INJECTION | 210 | 7 | PRD10215100 |