Biomarker-Guided Dosing Interval Extension of Mepolizumab and Dupilumab in Severe Asthma: A Clinical Evaluation

The primary objective of the BIRDIE trial is to assess the feasibility of extending the dosing interval of **mepolizumab** in patients with severe eosinophilic asthma, using eosinophil levels as a biomarker, without compromising asthma control. Additionally, the trial aims to evaluate the possibility of extending the dosing interval of **dupilumab** in patients with severe T2-high asthma, guided by FeNO levels as a biomarker, while maintaining asthma control. These objectives are clinically relevant as they explore potential strategies to optimize treatment regimens for severe asthma, potentially improving patient outcomes and reducing treatment burden.

The clinical trial involves participants diagnosed with **severe asthma**, specifically those who have been receiving treatment with mepolizumab or dupilumab for the past six months. The study population includes both male and female subjects, with an age range spanning from 18 to 65 years. Participants are required to have stable asthma, indicated by an Asthma Control Questionnaire (ACQ) score of less than 1.5 and no severe asthma exacerbations for at least six months. The trial does not include a vulnerable population. Participants must have a sufficient understanding of the Dutch language. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity are not specified in the trial data.

The clinical trial is designed to evaluate the possibility of extending the dosing interval of **mepolizumab** and **dupilumab** in patients with severe asthma, using specific biomarkers to guide the dosing schedule. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thereby minimizing bias. The trial is expected to last until September 2026, with recruitment starting in September 2023. Participants will be involved in the study for a maximum treatment period of 12 months.

The sequence of study visits begins with an inclusion visit, where participants are screened based on criteria such as having severe asthma as the primary indication for treatment with either mepolizumab or dupilumab for the last six months, stable asthma, and sufficient understanding of the Dutch language. Follow-up visits will occur regularly to monitor the number of injections received and assess asthma control. The primary endpoint is the number of injections administered during the follow-up period. The study concludes with an end-of-study visit to evaluate the overall outcomes and any potential adverse effects.

Participants may be terminated early from the study if they experience severe asthma exacerbations or if they no longer meet the inclusion criteria. The trial aims to ensure that the additional procedures do not pose more than minimal additional risk to the safety of subjects compared to normal clinical practice. The study is not classified as low intervention, and both investigational medicinal products are used in accordance with their marketing authorization terms.

The clinical trial involves the administration of **Dupilumab**, marketed under the name Dupixent, which is provided as a 100 mg **solution for injection** in a pre-filled syringe. This experimental medication is administered via **subcutaneous injection**. The maximum daily dose is 300 mg, with a total maximum dose of 300 mg over a treatment period of up to 12 months. Dupilumab is a protein-based therapeutic agent, specifically classified as "Protein - Other," and is produced by Sanofi Winthrop Industrie. The dosing schedule is determined by the trial protocol, and participant compliance is monitored throughout the study.

Another experimental medication used in the trial is **Mepolizumab**, marketed as Nucala, which is provided as a 100 mg **powder for solution for injection**. Similar to Dupilumab, Mepolizumab is administered via **subcutaneous injection**. The maximum daily dose is 100 mg, with a total maximum dose of 100 mg over a treatment period of up to 12 months. Mepolizumab is also a protein-based therapeutic agent, classified as "Protein - Other," and is manufactured by GlaxoSmithKline Trading Services Limited. The administration and dosing schedule are guided by the trial protocol, with participant compliance being closely monitored.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data. The trial aims to evaluate the possibility of extending the dosing interval of these biologics, driven by specific biomarkers, in patients with severe eosinophilic asthma and severe T2-high asthma, without loss of asthma control. Compliance with the dosing schedule and monitoring of participant adherence are integral components of the trial to ensure the validity and reliability of the study outcomes.

Efficacy in the clinical trial titled "BIomarker-dRiven Dosing Interval Extension of biologics in asthma (the BIRDIE trial)" will be assessed primarily by evaluating the number of injections administered in the **mepolizumab** and **dupilumab** intervention groups during the follow-up period. This endpoint is designed to determine if the dosing interval of these biologics can be extended without loss of asthma control, driven by specific biomarkers. For **mepolizumab**, the biomarker used is eosinophil levels, while for **dupilumab**, the biomarker is FeNO (Fractional exhaled Nitric Oxide) levels. The trial aims to assess whether these biomarkers can guide the extension of dosing intervals in patients with severe eosinophilic asthma and severe T2-high asthma, respectively.