Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2026
Protocol for a multinational, investigator-initiated, parallel-group, randomized, double-blind, placebo-controlled phase 3b superiority trial assessing the effect of dupilumab on inducing clinical remission outcomes in at-risk type-2 inflammatory asthma (HOTHOT).
Протокол клинического исследованияСтатьяНазвание и аннотация: Перевод в очереди
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Couillard Simon, Petousi Nayia, Ramakrishnan Sanjay, Valle Renzo, Tétu Amelie, Lemaire-Paquette Samuel, Xia Changming, Poirier Steve, Ledanois Olivier, Gall Rebecca, Côté Andréanne, Diab Nermin, Lachapelle Philippe, Pavord Ian D
Аннотация
INTRODUCTION: Asthma is a prevalent chronic respiratory disease in which up to 44% of patients require systemic corticosteroids annually. Many have active type-2 inflammation, characterized by elevated blood eosinophils and/or fractional exhaled nitric oxide (FeNO), type-2 biomarkers that predict asthma attacks and lung function decline. Biologics such as the interleukin-4/13 targeting dupilumab have exhibited efficacy in patients with moderate-to-severe asthma and raised type-2 biomarkers, yet their role in inducing clinical remission earlier in the disease course remains untested. We speculate that dupilumab intervention can induce clinical remission in adults with at-risk type-2 inflammatory asthma.
METHODS AND ANALYSIS: We report the protocol for a multinational, investigator-initiated, parallel-group, randomized, double-blind, placebo-controlled, phase 3b superiority trial (HOTHOT). Adults with established asthma, blood eosinophils of at greater than or equal to 0.3 × 109/L, FeNO greater than or equal to 35 parts per billion, and at least 1 severe asthma attack in the past 24 months and maintained on at least medium-dose inhaled corticosteroids (ICS) will be eligible. A total of 150 participants will be randomized 1:1 to fortnightly dupilumab or volume-matched placebo for more than 56 weeks. Background ICS therapy will be adjusted every 3 months on the basis of symptoms and spirometry, blinded to biomarker data. The primary end point is the win ratio on the basis of remission criteria at week 56, hierarchically comparing absence and number of severe attacks, preserved forced expiratory volume in 1 second, maintenance on medium-dose ICS or less, and 5-item asthma control questionnaire score less than 1.5. Secondary outcomes include the annualized severe attack rate, remission win ratio in the medium-dose ICS subgroup, change in forced expiratory volume in 1 second, and a binary remission end point.
ETHICS AND DISSEMINATION: The study is approved by the Research Ethics Committee of the Integrated University Health and Social Services Centre de l'Estrie- Centre Hospitalier Universitaire de Sherbrooke (MP-31-2026-6116). The protocol follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2025 guidelines. Results will be disseminated at international meetings and in peer-reviewed journals in accordance with the Consolidated Standards of Reporting Trials.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT07309614.
METHODS AND ANALYSIS: We report the protocol for a multinational, investigator-initiated, parallel-group, randomized, double-blind, placebo-controlled, phase 3b superiority trial (HOTHOT). Adults with established asthma, blood eosinophils of at greater than or equal to 0.3 × 109/L, FeNO greater than or equal to 35 parts per billion, and at least 1 severe asthma attack in the past 24 months and maintained on at least medium-dose inhaled corticosteroids (ICS) will be eligible. A total of 150 participants will be randomized 1:1 to fortnightly dupilumab or volume-matched placebo for more than 56 weeks. Background ICS therapy will be adjusted every 3 months on the basis of symptoms and spirometry, blinded to biomarker data. The primary end point is the win ratio on the basis of remission criteria at week 56, hierarchically comparing absence and number of severe attacks, preserved forced expiratory volume in 1 second, maintenance on medium-dose ICS or less, and 5-item asthma control questionnaire score less than 1.5. Secondary outcomes include the annualized severe attack rate, remission win ratio in the medium-dose ICS subgroup, change in forced expiratory volume in 1 second, and a binary remission end point.
ETHICS AND DISSEMINATION: The study is approved by the Research Ethics Committee of the Integrated University Health and Social Services Centre de l'Estrie- Centre Hospitalier Universitaire de Sherbrooke (MP-31-2026-6116). The protocol follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2025 guidelines. Results will be disseminated at international meetings and in peer-reviewed journals in accordance with the Consolidated Standards of Reporting Trials.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT07309614.