Potency of HDM Sublingual AIT Tablets in Assuring the Persistency of Asthma Control in HDM Allergic Patients With Severe Asthma, Treated With Tezepelumab

Обзор

The aim of this drug trial is to evaluate the annualized asthma exacerbation rate under treatment with Acarizax versus placebo. The trial is intended for adults aged 18 to 65 with severe uncontrolled asthma and a house dust mite allergy. The study will involve 32 patients (up to 38 with study dropouts) recruited from French hospitals, in pulmonology and allergology departments. Initially, all participants will receive Tezepelumab for 3 to 6 months (M-3/-6) to control asthma symptoms. If asthma is not controlled after 6 months, the participant will be excluded from the study and will continue on standard treatment. Once their asthma is controlled, patients will be randomized in two groups: * Group A: Tezepelumab + Acarizax® * Group B: Tezepelumab + Placebo After 6 months of treatment with Acarizax or placebo (M6), Tezepelumab will be stopped and participants will continue treatment with Acarizax or placebo alone for a further 12 months (up to M18/End of search). The study will include 5 visits during regular consultations (M-3/M-6, D0, M6, M12 and M18), as well as 2 follow-up telephone calls M3 and M9).

Подробное описание

The TEZEPAIT study is a prospective, multicentre, 2-parallel-arms, placebo-controlled, double-blind, randomized (1:1) trial.

PHASE 1: Patients will be included in the study after verification of eligibility criteria and signing of informed consent. All patients will be treated with Tezepelumab for 3-6 months and randomized in two groups:

* Group A: Tezepelumab + Acarizax® * Group B: Tezepelumab + Placebo If patients are not controlled (ACT ≥ 20/25) after 3 months of Tezepelumab, they will be re-assessed monthly, for 3 consecutive months, until asthma symptoms are controlled or they will be excluded from the rest of the study. If they are not controlled after 6 months, they will be excluded from the study.

PHASE 2: After the phase 1, if asthma symptoms are controlled (Asthma Control Test, ACT ≥20/25), patients in Group A will start Acarizax®, in addition to Tezepelumab, while patients in Group B will continue Tezepelumab plus a placebo. Patients will all receive a 6-month treatment of Acarizax® or placebo, before stopping Tezepelumab (M6), to assure an optimal effect of AIT, as shown in Phase 3 trials.

Patients will all receive an additional 6 months of Tezepelumab starting at D0 (Start of Acarizax®/placebo), before stopping it.

PHASE 3: After stopping Tezepelumab, patients will receive an additional 12-month treatment of Acarizax® or placebo. Patients will receive an 18-month course of Acarizax® or placebo.

For safety and ethical reasons, between M6 and M18 (Tezepelumab treatment will be suspended), in case of reappearance of uncontrolled severe asthma, Tezepelumab will be re-prescribed to patients.

At the end of the study, patients on placebo, if their asthma is controlled, will be offered Acarizax® treatment (as a regular prescription and paid / reimbursed as proposed by the National French HealthCare system) and patients on Acarizax® treatment and controlled will be able to continue it as routine care.

Вмешательства

• Препарат Tezepelumab
  Patients will take Tezepelumab for 3 to 6 months (M-3/-6) to control asthma symptoms. Once asthma symptoms are controlled (D0), patients will take an additionnal of 18 months of Tezepelumab
• Препарат Acarizax
  Once asthma symptoms are controlled (D0), patients will take 18 months of Acarizax.
• Препарат Placebo
  Once asthma symptoms are controlled (D0), patients will take 18 months of Placebo.

Первичные конечные точки

• Annualized total number of asthma exacerbations under acarizax/placebo treatment [Срок оценки: Between Day 0 and Month 18]

Вторичные конечные точки (12)

• Annualized total number of asthma exacerbations without Tezepelumab [Срок оценки: Between Month 6 and Month 18 (during 21 to 24 months)]
• ACT score [Срок оценки: At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 3, Month 6, Month 9, Month 12 and Month 18]
• ARCT score only for patients suffering from allergic rhinitis [Срок оценки: At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 3, Month 6, Month 9, Month 12 and Month 18]
• Forced Expiratory Volume (FEV1) [Срок оценки: At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 6, Month 12 and Month 18]
• Forced vital capacity (FVC) [Срок оценки: At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 6, Month 12 and Month 18]
• Modified Tiffeneau-Pinelli index [Срок оценки: At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 6, Month 12 and Month 18]
• Rate of Eosinophils [Срок оценки: At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 6, Month 12 and Month 18]
• Total and Specific IgE levels [Срок оценки: At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 6, Month 12 and Month 18]
• Specific IgG4 levels [Срок оценки: At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 6, Month 12 and Month 18]
• Eosinophil-Derived Neurotoxin (EDN) levels [Срок оценки: At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 6, Month 12 and Month 18]
• Cytokines IL-4, IL-5, IL-13 [Срок оценки: At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 6, Month 12 and Month 18]
• SGRQ score [Срок оценки: Month 3, Month 6, Month 9, Month 12 and Month 18]

Критерии участия

Критерии включения

• Patients aged ≥ 18 years and ≤ 65 years.
• Patient followed by a specialist in allergy and/or respiratory diseases working at one of the investigating sites in France.
• Patient allergic to HDM and with a clinical history of HDM-allergic asthma.
• Positive specific IgE (≥ 0.35 kUA/L, ImmunoCAP®) and positive skin prick test for Dermtophagoides pteronyssinus and/or Dermtophagoides farinae at screening.
• Patients satisfying diagnostic criteria for severe asthma, according to GINA international guidelines.
• A clinical history of asthma exacerbations in the past two years.
• A history of at least 2 asthma exacerbations during the previous 12 months.
• Uncontrolled asthma (ACT <20/25)
• Lung function measured by FEV1 ≥ 70% of predicted value or according to local requirements.
• Patients with persistent severe asthma who meet the Marketing Authorization criteria for Tezspire® (Tezepelumab) and Acarizax® prescriptions.

Критерии исключения

• Patients sensitized and regularly exposed to animal dander, molds, and/or cockroach or any another perennial allergen.
• Patients treated with a monoclonal antibody for asthma within the previous 3 months or 5 half-lives.
• Patients who have received Sublingual immunotherapy (SLIT) or Sub-Cutaneous Immunotherapy (SCIT) treatment with DermatophagoIdes pteronyssinus and/or Dermatophagoïdes farinae within the previous 5 years.
• Patients received any education provided by a medical indoor environment counselor during the 12 months before the study, or and educational program is programmed during the study.
• Patients with acute respiratory tract infections.
• The patient who have performed any specific measure for mites' avoidance during the 12 months before the study or plan to implement such measures during the study.
• Pregnant, breastfeeding or lactating women.
• Patients with a history of tumor, autoimmune, or immune deficiency pathology.
• Patients with hematological pathology (coagulation disorders, anemia) that could interfere with the blood test.
• The patient reports any previous hypersensitivity reaction to the active substance or excipients present in Tezspire® or Acarizax®.
• Patients unable to read and/or write French language.
• Absence of signed consent.
• Patients who are not beneficiaries of the French social security system.
• Presence of any condition (physical, psychological or other) that might, in the investigator's opinion, hinder study performance.
• The patient is unavailable or unwilling to participate in future visits or is unable to comply with trial protocol.
• Women of childbearing potential and fertile men not using effective contraception.
• The patient is participating in another study for asthma and/or allergy treatment.
• Patients in an exclusion period determined by a previous study or is currently participating to any other allergy/asthma trial.
• Patients under legal protection (guardianship or curatorship)
• Patients with a business or personal relationship with trial staff or sponsor who is directly involved with the conduct of the trial.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Поддерживающая терапия

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Seys SF, Scheers H, Van den Brande P, Marijsse G, Dilissen E, Van Den Bergh A, Goeminne PC, Hellings PW, Ceuppens JL, Dupont LJ, Bullens DM. Cluster analysis of sputum cytokine-high profiles reveals diversity in T(h)2-high asthma patients. Respir Res. 2017 Feb 23;18(1):39. doi: 10.1186/s12931-017-0524-y. PMID 28231834
• Lommatzsch M, Brusselle GG, Canonica GW, Jackson DJ, Nair P, Buhl R, Virchow JC. Disease-modifying anti-asthmatic drugs. Lancet. 2022 Apr 23;399(10335):1664-1668. doi: 10.1016/S0140-6736(22)00331-2. No abstract available. PMID 35461560
• Corren J, Larson D, Altman MC, Segnitz RM, Avila PC, Greenberger PA, Baroody F, Moss MH, Nelson H, Burbank AJ, Hernandez ML, Peden D, Saini S, Tilles S, Hussain I, Whitehouse D, Qin T, Villarreal M, Sever M, Wheatley LM, Nepom GT, Sanda S; Immune Tolerance Network ITN057AD CATNIP Study Team. Effects of combination treatment with tezepelumab and allergen immunotherapy on nasal responses to allergen PMID 36223848
• Fritzsching B, Contoli M, Porsbjerg C, Buchs S, Larsen JR, Elliott L, Rodriguez MR, Freemantle N. Long-term real-world effectiveness of allergy immunotherapy in patients with allergic rhinitis and asthma: Results from the REACT study, a retrospective cohort study. Lancet Reg Health Eur. 2021 Nov 30;13:100275. doi: 10.1016/j.lanepe.2021.100275. eCollection 2022 Feb. PMID 34901915
• Corren J, Parnes JR, Wang L, Mo M, Roseti SL, Griffiths JM, van der Merwe R. Tezepelumab in Adults with Uncontrolled Asthma. N Engl J Med. 2017 Sep 7;377(10):936-946. doi: 10.1056/NEJMoa1704064. PMID 28877011
• Agache I, Rogozea L. Asthma Biomarkers: Do They Bring Precision Medicine Closer to the Clinic? Allergy Asthma Immunol Res. 2017 Nov;9(6):466-476. doi: 10.4168/aair.2017.9.6.466. PMID 28913985
• Influence of diet on fatty acid composition of red cell and neural membranes. Nutr Rev. 1987 Aug;45(8):246-8. doi: 10.1111/j.1753-4887.1987.tb02690.x. No abstract available. PMID 3306486
• Gauvreau GM, Sehmi R, Ambrose CS, Griffiths JM. Thymic stromal lymphopoietin: its role and potential as a therapeutic target in asthma. Expert Opin Ther Targets. 2020 Aug;24(8):777-792. doi: 10.1080/14728222.2020.1783242. Epub 2020 Jun 27. PMID 32567399

Идентификаторы

NCT: NCT07013123 · RECHMPL25_0069 · 2025-521258-41-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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