Predictive Signature of Benralizumab Response

Обзор

The objective of the study is to establish the predictive value of early blood gene expression signature of Benralizumab response associated with a significant reduction of the number of exacerbations in treated severe asthmatic patients. This trial is a French, multicenter and no-randomized trial. Patients enrolled will be clinically followed for 16 months (the treatment period: 12 months and 1 month follow-up; 6 clinical visit on site and in phone call at 13 months)

Вмешательства

• Препарат Benralizumab Prefilled Syringe
  Patients receive BENRALIZUMAB if they meet the criteria for inclusion and non-inclusion at the inclusion visit. Injections take place at the inclusion visit, at 1 month, 2 months, 4 months, 6 months, 8 months, 10 months and 12 months.

Первичные конечные точки

• Predictive value of early blood gene expression signature of Benralizumab [Срок оценки: 12 months]

Вторичные конечные точки (6)

• Molecular signature predictive of stabilization [Срок оценки: 12 months]
• The stability of the signature over time [Срок оценки: 0 month, 3 months, 6 months and 9 months]
• The association of gene expression patterns [Срок оценки: 12 months]
• Association of gene expression patterns and clinical characteristics [Срок оценки: 0 months]
• Stratification value of gene expression in severe asthma [Срок оценки: 12 months]
• Scenario-based cost-utility analysis [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Patients between 18 and 75 years old.
• Patients diagnosed with severe asthma (Chung and al, Eur Respir J 2014), i.e.:

• asthma requiring high doses of ICS (>1000 microgram per day of Beclomethasone or equivalent) associated with LABA and/or systemic corticosteroids to be controlled over one year,
• and/or uncontrolled asthma despite the later medications,
• and/or a controlled asthma worsening after decreasing medications,
• Documented historical reversibility of FEV1 ≥12% and FEV1 gain ≥ 200 milliliter
• ACQ-7 score ≥ 1,5 at M0.
• ≥ 3 exacerbations in the 12 months prior to screening visit M-1.
• Eosinophil blood count ≥ 0,3 G/L at inclusion visit or in the 12 months prior to the inclusion visit. If eosinophil blood count is ≥ 0,15 G/L and < 0,3 G/L, an eosinophilic phenotype defined by at least 1 of the following criteria will be required:

• Fractional Exhaled Nitric Oxide (FeNO) > 25 ppm at inclusion visit or in the 12 months prior to the inclusion visit.
• Sputum eosinophils ≥ 3% at inclusion visit or in the 12 months prior to the inclusion visit.
• Patients who provide written informed consent prior to participation in the study

Критерии исключения

• Patients diagnosed with difficult-to-treat asthma and/or with uncontrolled asthma differential diagnosis according to the judgment of the investigator (e.g., vocal cord dysfunction, gastroesophageal reflux disease, granulomatous eosinophilic vasculitis, obstructive sleep apnea syndrome, hyperventilation syndrome, allergic broncho-pulmonary aspergillosis, Carrington disease, DIPNECH, asthma/COPD overlap syndrome).
• Non-adherent patients to inhaled treatment (ICS + LABA).
• Active smokers or former smokers exceeding 20 packs year.
• Exacerbation at inclusion visit M0.
• Active malignancy or malignancy in remission over less than 5 years.
• Active parasitic infection or parasitic infection in the past 24 weeks.
• Hypersensitivity to Benralizumab or to any of the excipients of Fasenra® (histidine, histidine hydrochloride monohydrate, trehalose dihydrate, polysorbate 20)
• Patients requiring other immunosuppressive and immunomodulator drugs
• Patients requiring other biotherapy than Benralizumab, with or without French's marketing authorisation in severe asthma
• Patients requiring other biotherapy than Benralizumab that affects the immune system
• SARS-COV2 infection
• Pregnancy, lactation, or patients with childbearing potential refusing efficient contraceptive method.
• Patients under psychiatric condition altering their comprehension and their ability to give informed consent.
• Patients already enrolled in a clinical interventional research.
• Patients not affiliated to a health insurance plan
• Patients under guardianship, curators or safeguard of justice

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Франция · 20 центров

• Centre hospitalier Intercommunal Aix-en-Provence — Aix-en-Provence
• CHU Angers — Angers
• CHU Bordeaux — Bordeaux
• CHRU Brest — Brest
• CHU Dijon — Dijon
• CHU Grenoble — Grenoble
• Hôpital Bicêtre - AP-HP — Le Kremlin-Bicêtre
• CH Mans — Le Mans
• … и ещё 12 центров

Идентификаторы

NCT: NCT04565483 · RC19_0292

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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