Testing Dupilumab Prefilled Syringe against a placebo for asthma control

Inclusion

• +Study participants are eligible to be included in the study only if all of the following criteria apply:
• +Participant must be 18-\<80 years of age at the time of signing the informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more →.
• +Type of participant and disease characteristics
• +Physician diagnosis of asthma (according to GINA 2025) for ≥6 months, with documented historical airflow variability by one of the following:
• +Positive reversibility test: ≥12% and 200 ml in FEV1 after SABA administration at any point prior to randomisationRandomisedWhich group you go into is decided by chance, not by you or your doctor.Read more →
• +Airflow variability in clinic FEV1 \>12% and 200 mL between historical clinical visits
• +Positive bronchial challenge test: fall in FEV1 of ≥20% with standard doses of methacholine (\<16 mg/mL or \<400mcg); or ≥10% with standardised hyperventilation, or exercise challenge test; or ≥15% with hypertonic saline or mannitol challenge
• +Peak flow variability of \>20% between two assessments
• +Evidence of elevated type-2 biomarkersBiomarkerSomething measurable in the body used as a signal of what is happening.Read more → defined as both of:
• +peripheral BEC ≥ 0.3×109/L at screening visitScreeningThe checks done before joining, to see whether a study fits.Read more →
• +FeNO ≥ 35 ppb at screening visit
• +At least 1 asthma attack in the last 2 years, defined as acute asthma requiring SCS for ≥ 3 days or an emergency/hospital visit requiring SCS.
• +Treatment and evident adherence to a stable at-least medium-dose ICS (fluticasone propionate equivalent \>250 mcg/day) for at least 3 months (including run-in periodRun-in periodA short trial period before the study proper begins.Read more →) \[additional controllers e.g. LABA, LAMA or LTA are allowed\]. 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 stratifiedStratificationSplitting participants into subgroups first, so groups stay balanced.Read more → by these categories.
• +Presence of one (or more) of the following additional risk factors for asthma attacks32 at screening or baselineBaselineYour starting measurements, taken before treatment begins.Read more →: (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-\<12 months.
• +Female participants
• +i. Is a woman of nonchildbearing potential (WONCBP) as defined in the Study Manual.
• +Informed consent
• +Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocolProtocolThe detailed plan a study must follow.Read more →.
• +EXCLUSION CRITERIAExclusion criteriaThe things that would prevent someone from taking part.Read more →
• +Participants are excluded from the study if any of the following criteria apply:
• +Medical conditions
• +Use of SCS \< 1 months prior to screening or on maintenance SCS.
• +Documented nonadherence to ICS, defined as dispensing of less than 75% of the prescribed ICS dose over the past 12 months (or annualised if less than 12 months), based on pharmacy refill records checked at screening.
• +Presence of significant and uncorrectable inhaler technique deficiencies, as assessed by the research team during inhaler technique evaluation at screening.
• +Contra-indication to study drug
• +Immunological disease, condition or medication that may affect the inflammatory response according to InvestigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →.
• +History of other significant lung disease e.g. lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, clinically significant bronchiectasis, chronic obstructive lung disease, or Churg-Strauss.
• +Severe concomitant illness (including known or suspected immunodeficiency) that, in the Investigator's judgement will adversely affect the participant's participation in the study.
• +Active malignancy or history of malignancy within 5 years (except for basal cell carcinoma of the skin or fully resected Cervical Intraepithelial Neoplasia/dysplasia).
• +Exposure to monoclonal antibody therapy for asthma or another investigational medicinal product within 5 half-lives of the drug.
• +EligibilityEligibility criteriaThe full list of requirements for taking part in a study.Read more → to Dupilumab based on licensed and reimbursed indications in the participant's jurisdiction (e.g. nasal polyposis, atopic dermatitis, eosinophilic esophagitis, prurigo nodularis, etc.)
• +Treatment with live (attenuated) vaccine in the past 4 weeks.
• +Prohibited medication 15 Current helminth infection
• +Sex, contraceptive/barrier method and pregnancy testing requirements
• +a. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• +OR ii. Is a WOCBP and agrees to use a contraceptive method that is highly effective, with a failure rate of \<1%, during the intervention period (to be effective before starting the intervention) and for at least 12 weeks after the last dose of study intervention.
• +b. A WOCBP must have a negative highly sensitive serum pregnancy test at V1 (screening visit) and urine or serum pregnancy test (as required by local regulations) on Day 1 before the first dose of study intervention, c. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• +d. Additional requirements for pregnancy testing during and after study intervention are imposed.
• +e. The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusionInclusion criteriaThe things you must have or be for a study to consider you.Read more → of a female participant with an early undetected pregnancy.
• +Current tobacco smoker or recently stopped smoker (\<6 months)
• +Ex-smoker with greater than 10 pack-years AND post bronchodilator FEV1/FVC ratio below the lower limit of normal according to GLI race-neutral standards. 69