Allergy to House Dust Mites, Severe Asthma
Conditions
Keywords
Asthma, Dust Mite Allergy, Allergen immunotherapy
Brief summary
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).
Detailed description
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.
Interventions
DRUGTezepelumab
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
DRUGAcarizax
Once asthma symptoms are controlled (D0), patients will take 18 months of Acarizax.
DRUGPlacebo
Once asthma symptoms are controlled (D0), patients will take 18 months of Placebo.
Sponsors
AstraZeneca
ALK-Abelló A/S
University hospital of Nîmes
ThermoFisher Scientific Brahms Biomarkers France
University Hospital, Montpellier
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Acarizax and placebo tablets will be reconstituted in the same shape.
Intervention model description
Once asthma symptoms are controlled (from D0), patients will receive: * Group A: 6 months of Tezepelumab and 18 months of Acarizax * Group B: 6 months of Tezepelumab and 18 months of Placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized total number of asthma exacerbations under acarizax/placebo treatment | Between Day 0 and Month 18 | The number of asthma exacerbations will be recorded by the participant in their follow-up diary throughout the Acarizax or placebo treatment period. Day 0 marks the start of Acarizax/placebo treatment, and Month 18 marks the end. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ACT score | At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 3, Month 6, Month 9, Month 12 and Month 18 | The primary purpose of the Asthma Control Test is to provide a systematic way to evaluate how well a patient's asthma is controlled. The test consists of 5 questions that cover different aspects of asthma control (Frequency of symptoms, limitations on Activities, Nighttime Symptoms, Need for rescue Medication, Self-Assessment). Each question is crafted to elicit information on the patient's experience over the past 4 weeks. The possible scores for each question range from 1 to 5. The total score can range from 5 to 25. A 2-points increase in the score has been proven to be statistically significant. |
| ARCT score only for patients suffering from allergic rhinitis | At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 3, Month 6, Month 9, Month 12 and Month 18 | This test has been validated for assessing allergic rhinitis control and identifying severe allergic rhinitis. The test consists of 5 questions that cover different aspects of allergic rhinitis (Impact on daily life, Quality of life, Nighttime Symptoms, Need for rescue Medication, Self-Assessment). Each question is crafted to elicit information on the patient's experience over the past 2 weeks. The total score can range from 5 to 25. A 2-points increase in the score has been proven to be statistically significant. |
| Forced Expiratory Volume (FEV1) | At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 6, Month 12 and Month 18 | Spirometry result: Forced Expiratory Volume in 1 second (L). |
| Forced vital capacity (FVC) | At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 6, Month 12 and Month 18 | Spirometry result: Forced Vital Capacity (L). |
| Modified Tiffeneau-Pinelli index | At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 6, Month 12 and Month 18 | Spirometry result: FEV₁/FVC ratio (%). |
| Rate of Eosinophils | At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 6, Month 12 and Month 18 | Rate of Eosinophils in peripheral blood (Cells/µL) |
| Annualized total number of asthma exacerbations without Tezepelumab | Between Month 6 and Month 18 (during 21 to 24 months) | The number of asthma exacerbations will be recorded by the participant in their follow-up diary throughout the entire trial. Month 6 marks the end of Tezepelumab treatment, and Month 18 marks the end of Acarizax/placebo treatment. |
| Specific IgG4 levels | At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 6, Month 12 and Month 18 | Serum levels of Specific IgG4 (kU/L) |
| Eosinophil-Derived Neurotoxin (EDN) levels | At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 6, Month 12 and Month 18 | Serum levels of eosinophil-derived neurotoxin (ng/mL) |
| Cytokines IL-4, IL-5, IL-13 | At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 6, Month 12 and Month 18 | Serum levels of IL-4, IL-5 and IL-13 (pg/mL) |
| SGRQ score | Month 3, Month 6, Month 9, Month 12 and Month 18 | The SGRQ is a 50-item questionnaire developed to measure health status (quality of life) in patients with diseases if airways obstruction. It has two parts: * Part I (8 Symptoms items): Several scales * Part II (8 sections on Activity and Impacts): Dichotomous (true/false) except last question (4-point Likert scale) Scores are calculated for 3 domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. Scores range from 0 to 100, with higher scores indicating more limitations. A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing. |
| GIRERD questionnaire score | Month 3, Month 6, Month 9, Month 12 and Month 18 | This questionnaire evaluate treatment adherence. The investigator asks 6 yes/no questions, or the patient answers them independently. Yes = 1 point, No = 0 points. Total score: 0 to 6. |
| Adverse events attributable to Tezspire® or Acarizax® | At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 3, Month 6, Month 9, Month 12 and Month 18 | All adverse events will be collected to assess their causality in relation to experimental and/or auxiliary treatments. |
| Total and Specific IgE levels | At the start of Tezepelumab treatment (Month -3/-6), Day 0, Month 6, Month 12 and Month 18 | Serum levels of total and specific IgE (kU/L) |
Contacts
Primary ContactDavide CAIMMI, MD, PhD
Backup ContactAmelie DENOUEL, CRA
Outcome results
None listed