A multicentre, randomised, double-blind, placebo-controlled, 12-week parallel-group trial to evaluate the efficacy and safety of oral BP1.7881 in adult patients with moderate-to-severe atopic dermatitis

Trial ID: 2022-502045-10-00
Protocol: P20-03
Sponsor: Bioprojet Pharma

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Diseases & Conditions

Dermatitis atopic

Objectives

The primary objective of this multicentre, randomised, double-blind, placebo-controlled, 12-week parallel-group trial is to evaluate the **safety** and **efficacy** of BP1.7881 in adult patients with moderate-to-severe **atopic dermatitis**. This is clinically relevant as it aims to determine the therapeutic potential and safety profile of BP1.7881, a dual histamine H1 and H4 receptors antagonist, which could offer a new treatment option for patients with this chronic inflammatory skin condition.

Secondary objectives include:

Evaluating the correlation between genotype, specifically the genetic polymorphism of cytochrome (CYP) isoforms CYP2D6 and CYP2C19, and uridyl glucuronyl transferase (UGT) isoform UGT1A9, and the pharmacokinetics of BP1.7881, including serum concentrations of BP1.7881 and its major identified metabolites, in all randomised patients.
Assessing the correlation between genotype and BP1.7881 efficacy variables in all randomised patients.

Participants

The clinical trial focuses on evaluating the safety and efficacy of BP1.7881 in patients diagnosed with **atopic dermatitis**. The study population includes both male and female participants aged 18 years and older. Participants are required to have a diagnosis of chronic atopic dermatitis, as defined by the American Academy of Dermatology consensus criteria, with the condition being present for at least 12 months prior to randomization. The trial includes individuals with moderate to severe atopic dermatitis, characterized by an Eczema Area Severity Index (EASI) score between 10 and 35, and an Investigator's Global Assessment (IGA) score of 3 or 4. Participants must also have a baseline Pruritus Numerical Rating Scale (NRS) average score for itch intensity between 4 and 10. The trial population was selected based on these criteria, and participants are expected to maintain stable use of specific skin moisturizers or emollients if applicable. The sponsor has not provided information regarding the total number of participants in the study.

Plans and Procedures

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of the investigational drug BP1.7881 in adult patients with moderate-to-severe **atopic dermatitis**. The trial will span a duration of 12 weeks, with participants randomly assigned to receive either the active treatment or a matching placebo. The primary objective is to assess the mean change from baseline in the Eczema Area Severity Index (EASI) score after 12 weeks of treatment. Secondary endpoints include the proportion of patients achieving significant improvements in EASI scores and pruritus scales.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age, diagnosis, and severity of atopic dermatitis. Following randomization, participants will attend regular follow-up visits to monitor treatment effects and safety. These visits will include assessments of skin condition, pruritus intensity, and any adverse events. The end-of-study visit will occur at the conclusion of the 12-week treatment period, where final evaluations will be conducted to determine the overall efficacy and safety of BP1.7881.

The expected length of participant involvement is approximately 12 weeks, with conditions for early termination including significant adverse events, non-compliance with study procedures, or withdrawal of consent. Participants are required to maintain stable use of any specific skin moisturizers and adhere to trial requirements, including the use of contraception for eligible individuals. The trial aims to provide valuable insights into the potential benefits of BP1.7881 for patients with atopic dermatitis, contributing to the understanding of its therapeutic profile.

Treatment

The clinical trial involves the administration of **BP1.7881**, an experimental medication formulated as a **film-coated tablet**. This investigational drug is a highly potent, selective, and orally active dual histamine H1 and H4 receptors antagonist. The pharmaceutical form is designed for **oral use**, with a maximum daily dose of 270 mg. The treatment period is set for 12 weeks, aligning with the trial's duration. The active substance, BP1.7881, is of chemical origin and is not a paediatric formulation. The trial aims to evaluate the safety and efficacy of BP1.7881 in adult patients with moderate-to-severe atopic dermatitis.

In addition to the experimental medication, a **matching film-coating placebo tablet** is utilized as a comparator treatment in this double-blind, placebo-controlled study. The placebo is designed to mimic the appearance of the BP1.7881 film-coated tablet, ensuring blinding of both participants and investigators. The placebo does not contain any active pharmaceutical ingredients and serves as a control to assess the true efficacy and safety of the experimental drug. The administration schedule for the placebo matches that of the BP1.7881, maintaining consistency in dosing frequency and duration across all study participants.

Efficacy

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints designed to evaluate the impact of BP1.7881 on patients with moderate-to-severe atopic dermatitis. The primary endpoint is the mean change from baseline in the **Eczema Area Severity Index (EASI)** score after 12 weeks of treatment with BP1.7881 compared to placebo. This endpoint will provide a quantitative measure of symptom improvement over the course of the trial.

Secondary endpoints include the proportion of patients achieving an Investigator’s Global Assessment (IGA) of clear (0) or almost clear (1) with an improvement from baseline of at least 2 points, as well as the proportion of patients achieving 75% and 90% improvement in EASI score. Additionally, the percent change from baseline in the Peak Pruritus Numerical Rating Scale (Peak Pruritus-NRS) will be evaluated, along with the proportion of patients experiencing a reduction in Peak Pruritus-NRS of at least 4 at all scheduled time points. The mean change in pruritus will also be assessed using the 5-D Pruritus Scale.

These efficacy parameters will be measured and collected at specified time points throughout the 12-week treatment period. The use of validated scales such as the EASI and IGA, along with patient-reported outcomes like the Peak Pruritus-NRS and 5-D Pruritus Scale, will ensure a comprehensive evaluation of the treatment's efficacy. Data analysis will focus on comparing the outcomes between the BP1.7881 treatment group and the placebo group to determine the therapeutic benefit of the investigational drug.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Written informed consent obtained prior to any trial-related procedures.
Male or female ≥18 years old.
Patient with a diagnosis of chronic atopic dermatitis (according to American Academy of Dermatology consensus criteria) that has been present for at least 12 months prior to randomisation.
Moderate to severe atopic dermatitis, defined in this trial as: a) Eczema Area Severity Index (EASI) ≥10 and ≤35 at screening and at randomisation, and b) Investigator’s global assessment (IGA) 3 or 4 on a 5-point scale at screening and before randomisation.
Baseline Pruritus Numerical Rating Scale (NRS) average score for itch intensity ≥4 and <10
With documented history (within 6 months before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks).
If the patient is using a specific skin moisturiser/emollients/ointments/bath substance, then the moisturiser should be maintained at a stable dose for at least the 10 consecutive days immediately before the randomisation visit and thereafter during the trial.
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, smartphone with internet access).
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.
Male patients who had a vasectomy, or who agree to use a reliable method of contraception (i.e., condoms) or practice total abstinence from sexual intercourse during the entire duration of the trial and 90 days after the last dose of the study drug.
If required, patient must be insured by appropriate national health insurance system.

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Exclusion Criteria

Has evidence of a skin disease different from atopic dermatitis that, in the opinion of the investigator, would confound the diagnosis or evaluation of atopic dermatitis disease activity (e.g., psoriasis, chronic actinic dermatitis).
Has current active skin infection that, in the opinion of the investigator, would confound the diagnosis or evaluation of atopic dermatitis disease activity.
Takes medications prohibited by the protocol (and will not stop and enter a wash-out period per protocol prior to randomisation) or requires the use of prohibited medications during the trial period or requires long-term treatment of a chronic disease with any medication which to the opinion of the investigator or the medical monitor may confound the study efficacy outcomes.
Is pregnant or lactating. Pregnancy is confirmed in WOCBP by a positive serum human chorionic gonadotrophin laboratory test (>5 mIU/mL).
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 (e.g., history of syncope).
Patient with 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 ms for males or ≥470 ms for females.
Patient with unstable concurrent disease including uncontrolled hyperthyroidism or other endocrine disease, uncontrolled gastrointestinal disease (e.g., active peptic ulcer), uncontrolled haematological disease, uncontrolled autoimmune disorder, or other that might affect the patient’s safety and/or interfere with the conduct of the trial 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 hepatitis B viral infection or is positive for hepatitis B 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.
Patient who has a laboratory abnormality at screening as follows:  ALT, aspartate aminotransferase (AST values >2 x upper limit of normal (ULN)  Total bilirubin >2 x ULN (unless patient has Gilbert Syndrome)  Serum creatinine value >2 x ULN  Absolute neutrophils count <1.0 x 109 cells/L  Platelets <100 x 109/L  or any other uncontrolled clinically significant laboratory abnormality that would affect interpretation of the trial data or the patient’s participation in the trial.
Past medical history record of, or current infection with human immunodeficiency virus (HIV).
History of hypersensitivity to any of the study drug constituents.
Current or recent history (less than one year) of alcohol or drug abuse.
Patients having received any other IMP 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).