Non-Inferiority Phase III Trial of Budesonide Orodispersible Tablets for Inducing Histological Remission in Adult Eosinophilic Esophagitis

The primary objective of this study is to demonstrate the **non-inferiority** of 1 mg twice daily versus 2 mg once daily budesonide orodispersible tablets for the induction of histological remission in adult patients with active **eosinophilic esophagitis** (EoE). This is clinically relevant as it aims to establish an effective dosing regimen that could potentially improve patient adherence and outcomes by offering a more flexible treatment option.

Secondary objectives include:

• To further assess EoE-associated clinical, endoscopic, and histological findings after 6 weeks of treatment with budesonide orodispersible tablets.
• To study safety and tolerability as assessed by adverse events and laboratory parameters.
• To assess patients' quality of life.

The clinical trial involves a total of **74 participants** diagnosed with **eosinophilic esophagitis**. The study population comprises both male and female subjects, aged between 18 to 75 years, who have an active symptomatic and histological condition. Participants were selected based on specific criteria, including a confirmed diagnosis of eosinophilic esophagitis and a minimum score of 4 points in the Patient's Global Assessment concerning the severity of symptoms at the baseline visit. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted. The selection process ensures that all participants have provided signed informed consent, confirming their voluntary involvement in the study.

The clinical trial is designed as a **double-blind**, double-dummy, randomized, parallel-group, non-inferiority phase III study. The primary objective is to evaluate the efficacy and tolerability of 2 mg once daily versus 1 mg twice daily **budesonide** orodispersible tablets for the induction of histological remission in adults with **eosinophilic esophagitis**. The trial is expected to run from May 21, 2021, to December 14, 2025, with a maximum treatment period of 6 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18 to 75 years), confirmed diagnosis of eosinophilic esophagitis, and active symptomatic and histological disease. Following the screening, eligible participants will be randomized to receive either the test or comparator treatment. The study includes follow-up visits to monitor the change in the peak eos/mm² hpf from baseline to week 6, as well as changes in the severity of dysphagia, odynophagia, and overall EoE symptoms. The primary endpoint is the proportion of patients achieving histological remission, while secondary endpoints include changes in the Eosinophilic Esophagitis Activity Index.

The expected length of participant involvement is approximately 6 weeks, with conditions for early termination including withdrawal of consent, adverse events, or non-compliance with the study protocol. The trial ensures that all participants provide signed informed consent before participation. The study is not categorized as low intervention and is conducted under the sponsorship of DR. FALK PHARMA G.M.B.H., with the investigational products being **budesonide** orodispersible tablets, administered orally.

The clinical trial involves the administration of **BUL03**, an experimental medication formulated as an **orodispersible tablet**. The active substance in BUL03 is **budesonide**, a corticosteroid used for its anti-inflammatory properties. The medication is administered orally, with a maximum daily dose of 2 mg and a total maximum dose of 94 mg over a treatment period of up to 6 weeks. The trial aims to evaluate the efficacy of a 2 mg once-daily dosage regimen in comparison to other dosing schedules. Participant compliance with the dosing regimen is monitored throughout the study.

In addition to BUL03, the trial includes a comparator treatment, **Jorveza 1 mg orodispersible tablets**, which also contains **budesonide** as the active ingredient. This medication is administered orally, with a dosing schedule of 1 mg twice daily, maintaining the same maximum daily and total dose limits as BUL03. The Jorveza tablets are used to assess the non-inferiority of the once-daily dosing regimen of BUL03. The pharmaceutical form and administration route are consistent with the experimental medication, ensuring a controlled comparison between the two treatment arms.

The study also incorporates a **placebo** in the form of an orodispersible tablet, which serves as a control to evaluate the efficacy of the active treatments. The placebo is designed to match the appearance and administration route of the active medications, ensuring blinding of participants and investigators. The placebo does not contain any active substance and is used to maintain the double-blind nature of the trial. Compliance with the placebo administration is monitored similarly to the active treatments.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint is the proportion of patients achieving **histological remission**. Secondary endpoints include changes in the peak eosinophil count per square millimeter in high-power fields (eos/mm² hpf) from baseline to week 6, changes in the severity of dysphagia and odynophagia, changes in the overall severity of eosinophilic esophagitis (EoE) symptoms, and changes in the total weekly Eosinophilic Esophagitis Activity Index.

The trial is designed to evaluate the non-inferiority of two dosing regimens of budesonide orodispersible tablets for the induction of histological remission in adults with active EoE. The efficacy parameters will be measured and collected at specified timepoints, with the primary endpoint being assessed at the end of the treatment period. The trial will utilize validated scales and laboratory tests to ensure accurate and reliable data collection and analysis. The study is a double-blind, double-dummy, randomized, parallel-group, non-inferiority phase III trial, ensuring rigorous assessment of the treatment's efficacy.