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

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.

Inclusion criteria

• 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.

Exclusion criteria

• 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.