Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating BP1.7881 Efficacy and Safety in Adult Eosinophilic Esophagitis Patients
- Trial ID
- 2023-508949-40-00
- Protocol
- P22-04 / BP1.7881
- Sponsor
- Bioprojet Pharma
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 2 trial is to evaluate the **histological changes** in eosinophil infiltration of the esophageal tissue in adult patients with eosinophilic esophagitis. This is clinically relevant as it aims to assess the potential of BP1.7881 to reduce eosinophil levels, which are a key pathological feature of eosinophilic esophagitis, thereby potentially improving patient outcomes.
Secondary objectives include evaluating the safety, tolerability, and efficacy of BP1.7881 in this patient population. These assessments are crucial for determining the overall therapeutic profile of BP1.7881, ensuring that it is not only effective but also safe for long-term use in managing eosinophilic esophagitis.
Participants
The clinical trial focuses on **eosinophilic esophagitis** and involves a study population comprising both male and female participants aged 18 years and older. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants were selected based on the presence of symptoms associated with eosinophilic esophagitis for at least four weeks prior to screening, and a confirmed diagnosis of the condition at screening. The trial includes individuals who are compliant with trial procedures, including esophagogastroduodenoscopies with biopsies, and who can adhere to trial requirements such as completing questionnaires and maintaining drug compliance. Female participants of childbearing potential are required to use a highly effective method of contraception during the trial and for one month after discontinuing the investigational medication. The trial population includes a vulnerable group, although specific lifestyle considerations such as diet or physical activity were not detailed in the provided data.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled**, parallel-group phase 2 study to evaluate the efficacy and safety of BP1.7881 in adult patients with **eosinophilic esophagitis**. The primary objective is to assess histological changes in eosinophil infiltration of the esophageal tissue. The trial will involve the administration of BP1.7881 in the form of an orodispersible tablet, with a maximum daily dose of 270 mg, over a treatment period of up to 22 weeks. The study will also include a matching orodispersible placebo tablet for control purposes.
The trial will commence with a screening visit to confirm the diagnosis of eosinophilic esophagitis and ensure that participants meet the inclusion criteria, such as being 18 years or older and having symptoms associated with the condition for at least four weeks prior to screening. Participants will be required to provide written informed consent before any trial-related procedures. The trial will include several follow-up visits to monitor the participants' response to the treatment and assess any changes in symptoms and histological markers. The primary endpoint is the proportion of patients achieving a peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf at week 12. Secondary endpoints include changes in the EoE-Dysphagia Assessment Questionnaire score, EoE-Endoscopic Reference Score, and histological scoring from baseline to week 12.
The estimated duration of the trial is from June 2024 to December 2025, with participant involvement expected to last up to 22 weeks. Conditions that may lead to early termination from the study include non-compliance with trial procedures, withdrawal of consent, or any adverse events that, in the opinion of the investigator, warrant discontinuation. The trial is not classified as a low-intervention study and is conducted under the sponsorship of BIOPROJET. The study will adhere to all ethical guidelines and regulatory requirements to ensure the safety and well-being of participants throughout the trial duration.
Treatment
The clinical trial involves the administration of **BP1.7881A**, an experimental medication formulated as an **orodispersible tablet**. This pharmaceutical form allows for oral administration, facilitating ease of use and compliance. The active substance, BP1.7881A, is of chemical origin and is developed by BIOPROJET. The maximum daily dose of BP1.7881A is 270 mg, with a total maximum dose of 41,580 mg over the course of the treatment period, which spans 22 days. The dosing schedule is designed to ensure optimal therapeutic outcomes while monitoring participant compliance through regular assessments.
In addition to the experimental medication, the study employs a **matching orodispersible placebo tablet** as a comparator treatment. The placebo is designed to mimic the appearance and administration route of the BP1.7881A tablet, ensuring the double-blind nature of the trial. The placebo does not contain any active pharmaceutical ingredients and serves as a control to evaluate the efficacy and safety of BP1.7881A in adult patients with eosinophilic esophagitis. The use of a placebo is critical in maintaining the integrity of the study's results by providing a baseline for comparison against the experimental treatment.
Efficacy
The efficacy of the investigational product BP1.7881 in the treatment of **eosinophilic esophagitis** will be assessed through a series of predefined endpoints. The primary endpoint is the proportion of patients achieving a peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high power field (eos/hpf) at week 12. Secondary endpoints include changes from baseline to week 12 in the total EoE-Dysphagia Assessment Questionnaire (EDAQ) score, the Eosinophilic Esophagitis-Endoscopic Reference Score (EoE-EREFS), and the EoE Grade and Stage Scores from the Histology Scoring System (EoE-HSS). Additionally, the percent change in peak esophageal intraepithelial eosinophil count will be evaluated.
These efficacy parameters will be measured and collected at baseline and at week 12, utilizing validated scales and histological assessments. The trial is designed as a multicentre, randomized, double-blind, placebo-controlled, parallel-group phase 2 study, ensuring rigorous evaluation of the treatment's efficacy. The histological changes in eosinophil infiltration of the esophageal tissue serve as the primary objective, providing a direct measure of the treatment's impact on the underlying pathology of eosinophilic esophagitis.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Written informed consent obtained prior to any trial-related procedures.
- Male or female ≥18 years old.
- Presence of EoE associated symptoms at least during the last 4 weeks prior to screening (e.g., symptoms may include dysphagia which require liquids, coughing or gagging, vomiting, or medical attention to obtain relief).
- A diagnosis of EoE confirmed at screening.
- To the opinion of the investigator the patient will be compliant to carry out the trial procedures, including both esophagogastroduodenoscopies with biopsies.
- Patients must have a cooperative attitude and be able to comply with the entire trial requirements and procedures (e.g., trial-related questionnaire, drug compliance, not use prohibited concomitant medications).
- Female patients: post-menopausal women having at least 12 months of natural (spontaneous) amenorrhea, or women of childbearing potential (WOCBP, defined as all women physiologically capable of becoming pregnant) using a highly effective method of contraception* for the duration of the trial and for one month after stopping the investigational medication.
- If required, patient must be insured by appropriate national health insurance system.
Exclusion Criteria
- Patient with any of the following disease: documented gastroesophageal reflux disease (note: reflux associated with EoE is not exclusionary), recurrent vomiting due to causes other than EoE, parasitic and fungal infections of the gastrointestinal tract, congenital esophageal rings, Crohn’s disease, periarteritis, allergic vasculitis, drug injury, connective tissue diseases, bullous pemphigoid, pemphigoid vegetans, graft-versus-host disease, achalasia, celiac disease, vasculitis, carcinoma of the esophagus.
- Critical esophageal stricture or stricture not allowing the passage of a diagnostic upper endoscope (e.g., with an insertion tube diameter > 9mm).
- Has a history of esophageal surgery or an esophageal dilation
- Initiation or change of a food-elimination diet or introduction of a previously eliminated food group in the 6 weeks prior to screening. Patient on a food-elimination diet must remain on the same diet throughout the study period.
- Contraindicated for esophageal biopsy for any reason (e.g., presence of varices at endoscopy).
- Current evidence of oropharyngeal or esophageal candidiasis or active infection with Helicobacter pylori.
- Commencement, cessation, or modification of the dosage schedule for allergen immunotherapy (oral or sublingual); participants maintaining a consistent dosage of these treatments for a minimum of one year before screening are eligible for inclusion in the study. However, they are prohibited from altering the dosage throughout the course of the study.Use of systemic corticosteroids within 12 weeks or swallowed corticosteroids within 8 weeks prior to screening.
- Use of systemic immunosuppressive or immunomodulating drugs within 6 months prior to screening (e.g., Dupilumab, Mepolizumab, Reslizumab, or other interleukin inhibitors, prostaglandin D2 receptor antagonist, montelukast, purine analogues, anti-TNF therapy, cromolyn, anti-IgE monoclonal antibody).
- Female patient: pregnant or lactating woman. [Pregnancy is confirmed by a positive serum human chorionic gonadotrophin laboratory test (> 5mIU/mL). Serum pregnancy test will be done at screening and urine test at randomization]
- History of significant cardiovascular disease, particularly recent history of myocardial infarction or unstable coronary artery disease, arrhythmias, congestive heart failure, uncontrolled arterial hypertension. Patient with a known history of long QT syndrome with or without history of syncope.
- Patient with a clinically significant deviation(s) from normal on 12-lead ECG that results in an active medical problem, as determined by the Investigator at screening or has a corrected QT interval using Fridericia’s formula (QTcF) ≥450 msec for males or ≥470 msec for females.
- Patient with unstable concurrent disease including: uncontrolled hyperthyroidism or other endocrine disease, uncontrolled gastrointestinal disease (e.g. active peptic ulcer), uncontrolled hematological disease, uncontrolled autoimmune disorders, or other that might affect the patient’s safety and/or interfere with the conduct of the study according to the Investigator’s judgement.
- Patient with known or history of malignancy within the past 5 years with the exception of adequately treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
- Established diagnosis of human immunodeficiency virus (HIV), hepatitis B viral infection or is positive for hepatitis surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) at screening or established diagnosis of hepatitis C viral infection or is positive for hepatitis C antibody at the time of screening visit.
- Patient who has a laboratory abnormality at screening.
- History of hypersensitivity to any of the study drug constituents.
- Sexually active male unless he uses a condom during intercourse while taking drug and for 90 days after stopping investigational medication.
- Current or recent history (less than one year) of alcohol or drug abuse.
- Patient having received any other investigational drug within the preceding 30 days, or a longer and more appropriate time as determined by the Investigator (e.g., approximately five half-lives of the previous investigational drug).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 01 Jun 2024 | 8 |
 Italy | Recruiting | 01 Jun 2024 | 16 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Matching orodispersible placebo tablet | Placebo | N/A | — | — | — | N/A |