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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bioprojet Pharma, Bioprojet Pharma

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

11 Aug 2023 → 24 Jun 2024

Decision date (initial)

2023-05-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Bioprojet Pharma

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the safety and efficacy of BP1.7881 in patients with atopic dermatitis.

Secondary objectives 2

1. To evaluate the correlation between genotype (i.e., genetic polymorphism of 2 cytochrome (CYP) isoforms CYP2D6 and CYP2C19 and one uridyl glucuronyl transferase (UGT) isoform UGT1A9) and BP1.7881 pharmacokinetics (serum concentrations of BP1.7881 and its major identified metabolites) in all randomised patients
2. To evaluate the correlation between genotype (i.e., genetic polymorphism of 2 cytochrome (CYP) isoforms CYP2D6 and CYP2C19 and one uridyl glucuronyl transferase (UGT) isoform UGT1A9 and BP1.7881 efficacy variables in all randomised patients

Conditions and MedDRA coding

Atopic dermatitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Written informed consent obtained prior to any trial-related procedures.
2. 2. Male or female ≥18 years old.
3. 3. 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.
4. 4. 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.
5. 5. Baseline Pruritus Numerical Rating Scale (NRS) average score for itch intensity ≥4 and <10
6. 6. 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).
7. 7. 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.
8. 8. 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).
9. 9. 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.
10. 10. 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.
11. 11. If required, patient must be insured by appropriate national health insurance system.

Exclusion criteria 14

1. 1. 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).
2. 2. Has current active skin infection that, in the opinion of the investigator, would confound the diagnosis or evaluation of atopic dermatitis disease activity.
3. 3. 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.
4. 4. Is pregnant or lactating. Pregnancy is confirmed in WOCBP by a positive serum human chorionic gonadotrophin laboratory test (>5 mIU/mL).
5. 5. 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).
6. 6. 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.
7. 7. 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
8. 8. 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.
9. 9. 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.
10. 10. 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.
11. 11. Past medical history record of, or current infection with human immunodeficiency virus (HIV).
12. 12. History of hypersensitivity to any of the study drug constituents.
13. 13. Current or recent history (less than one year) of alcohol or drug abuse.
14. 14. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change from baseline in EASI score after 12 weeks of treatment with BP1.7881 compared to placebo.

Secondary endpoints 6

1. Proportion of patients who achieved an Investigator’s Global Assessment (IGA) of clear (0) or almost clear (1) with an improvement from baseline ≥2 points
2. Proportion of patients who achieved 75% improvement in EASI score
3. Proportion of patients who achieved 90% improvement in EASI score
4. Percent change from baseline in peak pruritus numerical rating scale (Peak Pruritus -NRS)
5. Proportion of patients with improvement (reduction) of the Peak Pruritus -NRS ≥4 at all scheduled time points
6. Mean change in pruritus via the 5-D Pruritus Scale

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bioprojet Pharma

Sponsor organisation

Bioprojet Pharma

Address

9 Rue Rameau

City

Paris

Postcode

75002

Country

France

Scientific contact point

Organisation

Bioprojet Pharma

Contact name

Regulatory Affairs Director

Public contact point

Organisation

Bioprojet Pharma

Contact name

Regulatory Affairs Director

Third parties 11

Bioprojet Pharma

Sponsor organisation

Bioprojet Pharma

Address

9 Rue Rameau

City

Paris

Postcode

75002

Country

France

Locations

3 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications