Safety, Tolerability, PK and Efficacy of BEN2293 in mild-moderate AD
Research type
Research Study
Full title
A First-in-Human, Double-Blind, Randomised, Vehicle Controlled Phase I/II Proof of Concept Study to Investigate the Safety, Tolerability, Pharmacokinetics and Efficacy of BEN2293 in Patients with Mild to Moderate Atopic Dermatitis
IRAS ID
287013
Contact name
Alexander Thompson
Contact email
Sponsor organisation
Benevolent AI Bio Limited
Eudract number
2020-003143-28
Duration of Study in the UK
1 years, 5 months, 9 days
Research summary
Research Summary:
The purpose of this study is to test a drug called BEN2293 (the ‘study drug’) that is being developed for the treatment of mild to moderate atopic dermatitis (atopic eczema).\n\nBEN2293 is a potent and selective inhibitor of all three members of the tropomyosin receptor kinase (Trk) protein family: TrkA, TrkB and TrkC.\n\nThe main aims of this study are:\n• To assess the safety and tolerability of the study drug, \n• To investigate the plasma PK of BEN2293 \n• To investigate the effect of BEN2293 on pruritis in patients with mild to moderate Atopic Dermatitis(AD).\n• To investigate the effect of BEN2293 on clinical improvement of AD in patients with mild to moderate AD.\n\nUp to 130 male and female patients between the ages of 18 and 65 with mild to moderate atopic dermatitis will be included in this trial.\nThe study drug or placebo will be administered once or twice daily for between 7 - 28 days depending on which part of the study the patients are included in.\nThe patients will be administering the IMP to between 10-30% of their Body Surface Area (BSA), depending on the cohort/part of the study they are taking part in.Summary of Results:
BenevolentAI Bio Limited, sponsored the study and would like to share the results with the participants A First-in-Human, Double-Blind, Randomised, Vehicle-Controlled Phase I/II Proof of Concept Study to Investigate the Safety, Tolerability, Pharmacokinetics and Efficacy of BEN2293 in Patients with Mild to Moderate Atopic DermatitisBenevolentAI would like to thank all the participants that contributed to this important study in Atopic Dermatitis. The time and dedication given by the participants helped researchers learn more about the safety and benefits of applying BEN2293 (the study drug) versus placebo (the dummy drug).
Why was this research study conducted?
Atopic dermatitis, also known as eczema, is an inflammatory skin condition that causes the skin to become itchy, red, and sore. Some patients are affected by small patches and other patients with inflammation all over the body which impacts the quality of life.
With over 230 million people worldwide suffering from atopic dermatitis, many of the available treatments do not always work for everybody, and some have side effects which limit continuous use. Therefore, there is a need for new treatments for atopic dermatitis.
What was the purpose of the study?
The main aims of the study were:
• To assess how safe and tolerable BEN2293 was when applied to skin
• To see how much BEN2293 goes through the skin into the blood stream (blood levels)
• To see whether the study drug improves atopic dermatitis in participants
What happened during the study?
A total of 123 participants with mild to moderate atopic dermatitis volunteered to take part in the study and were treated up to twice daily for up to 28 days. The study was divided into 2 parts (A and B).
In Part A of the study, 32 participants were divided into 4 treatment groups as per the table below. 24 participants received the study drug BEN2293, and 8 participants received placebo.
Group Treatment type
1 BEN2293 ointment 0.25% or placebo applied once daily for 7 days to 10% of their body surface area
2 BEN2293 ointment 1% or placebo applied once daily for 7 days to 10% of their body surface area
3 BEN2293 ointment 0.25% or placebo applied once daily for 14 days to 30% of their body surface area
4 BEN2293 ointment 1% or placebo applied twice daily for 14 days to 30% of their body surface areaIn part B of the study, 91 participants were divided into 2 treatment groups as per the table below. 49 participants received the study drug BEN2293, and 42 participants received placebo.
Group Treatment type
1 BEN2293 ointment 1% applied once twice for 28 days to up on 33% of their body surface area
2 Placebo applied twice daily for 28 days to up on 33% of their body surface area
During the study, the study Doctors monitored participants progress by assessing blood and urine samples, checking heart health using an ECG and evaluating atopic dermatitis symptoms by asking the participants to complete questionnaires on how they are feeling and how the condition of atopic dermatitis is.
What were the results of the study?
This is a summary of the main results of the study. The results were analysed for 31 participants in part A (1 participant did not complete the study) and 80 participants in part B (11 participants did not complete the study).
The blood and urine tests for all study participants in both parts did not show any significant abnormalities that could be associated with the ointment application, except for one participant in part A who had out of range blood liver enzymes (transaminases) results and was referred to their treating Physician (GP). There were no safety concerns raised from the blood pressure and ECG assessments performed.
Biopsy samples taken during Part B of the study showed good absorption of BEN2293 into the skin. Further investigation was completed on the biomarkers (how well the body responds to a treatment for a disease or condition) which showed some trends of improvement of the skin, but they were not significant.
Overall, BEN2293 ointment mostly resulted in improved eczema symptoms, decreased eczema severity and increased quality of life. However, it was found that BEN2293 was probably of no significant benefit over using the placebo ointment.
What side effects did participants have during the study?
Not all participants in the study experienced side effects. The most common side effects were application site pain, pins and needles feeling on application site and itching. The majority of side effects were considered to be mild and no serious side effects were reported. No participant withdrew from the study because of a side effect that was considered to be related to study ointment treatment.
The table below shows the treatment related side effects in part A.
Side effect Placebo (out of 8 participants) Treatment groups - summary of all 4 groups (out of 24 participants) Overall (out of 32 participants)
Application site pain 1 (12.5%), 1 (4.2%) , 2 (6.3%)
Application site paraesthesia (pins and needles feeling) 0 (0%), 2 (8.3%), 2 (6.3%)
Application site rash 1 (12.5%), 0 (0%), 1 (3.1%)
High liver enzymes 0 (0%), 1 (4.2%),1 (3.1%)
Pruritis (itching) 1 (12.5%) 0 (0%),1 (3.1%)Application of BEN2293 at 1.0% for 28 days was considered to be safe and well tolerated and the safety profile was comparable to that of the placebo. The table below shows the treatment related side effects in part B.
Side effect Placebo (out of 42 participants) Treatment group (out of 49 participants) Overall (out of 91 participants)
Application site discomfort 0 (0%), 1 (2.0%), 1 (1.1%)
Application site pain 0 (0%) 1 (2.0%), 1 (1.1%)
Pain 0 (0%) 1 (2.0%), 1 (1.1%)
Insomnia (difficulty sleeping) 0 (0%), 1 (2.0%), 1 (1.1%) Eczema 0 (0%), 1 (2.0%), 1 (1.1%)
Hyperhidrosis (excessive sweating) 1 (2.4%) 0 (0%), 1 (1.1%)
Pain of skin 1 (2.4%), 0 (0%), 1 (1.1%)
Pruritis (itching) 0 (0%), 2 (4.1%), 2 (2.2%)REC name
South Central - Oxford B Research Ethics Committee
REC reference
20/SC/0327
Date of REC Opinion
30 Sep 2020
REC opinion
Further Information Favourable Opinion