A Study Assessing the Effect of Dupilumab on Inducing Clinical Remission in Asthma

This study tests whether an asthma medication called dupilumab can help people achieve complete asthma control (called "remission") when given earlier in their disease, before asthma becomes severe. Currently, most people with asthma only receive advanced treatments like biologics after their condition has worsened significantly and caused lung damage. This study explores whether treating high-risk patients earlier could prevent asthma attacks and lung function decline, potentially achieving remission before permanent damage occurs. The study is looking for adults aged 18-79 with moderate asthma who have had at least one asthma attack requiring steroid pills in the past 2 years, use medium or high-dose inhaled steroids regularly, have high levels of inflammation markers in their blood and breath tests, but don't yet meet criteria for severe asthma requiring biologic therapy. Participants receive either dupilumab or placebo injections every 2 weeks for one year, alongside their regular asthma medications. They attend clinic visits every 3 months for breathing tests, questionnaires, and safety monitoring. Neither participants nor doctors know who receives the real medication until the study ends. The goal is to learn whether early treatment with dupilumab helps more people achieve complete asthma control compared to standard care alone, potentially changing how asthma is treated from "waiting until severe" to "preventing severe disease." The study runs in Canada, the United Kingdom, and Australia, involving 150 participants

INCLUSION CRITERIA Study participants are eligible to be included in the study only if all of the following criteria apply: Age 1. Participant must be 18-\12% and 200 mL between historical clinical visits * Positive bronchial challenge test: fall in FEV1 of ≥20% with standard doses of methacholine (\250 mcg/day) for at least 3 months (including run-in period) \[additional controllers e.g. LABA, LAMA or LTA are allowed\]. The ICS dosage will be defined as the dosage received on a regularly basis, excluding extra reliever doses taken in the context of anti-inflammatory reliever (AIR) therapy from the calculation. AIR is allowed in the context of the study. Thus, the high-dose ICS trial population (fluticasone propionate equivalent \>500 mcg/day)\* will represent patients who are not meeting the exacerbation criteria for biological reimbursement. \*As per section 6.2, we will cap recruitment to 60% of target population on medium-dose ICS, 40% on high-dose ICS, with randomisation also stratified by these categories. 6. Presence of one (or more) of the following additional risk factors for asthma attacks32 at screening or baseline: (i) uncontrolled asthma symptoms indicated by ACQ5 score of ≥ 1.5; (ii) impaired lung function indicated by post-bronchodilator FEV1 of ≤ 80% predicted; (iii) high-dose maintenance ICS therapy (iv) severe asthma attack in past 1-\