*A first in human, single and multiple ascending dose study of AX-202
Research type
Research Study
Full title
A first-in-human, randomised double-blind, placebo-controlled 2-part study to evaluate the safety, tolerability, immunogenicity and pharmacokinetics of single ascending doses of AX-202 in healthy subjects and multiple ascending doses of AX-202 in patients with mild to moderate chronic plaque psoriasis.
IRAS ID
1006661
Contact name
Sylvia Vetrhus
Contact email
Sponsor organisation
Arxx Therapeutics
Eudract number
2022-002534-13
ISRCTN Number
ISRCTN79668046
Research summary
Research Summary
The Sponsor, Arxx Therapeutics, is developing a new experimental medication called AX-202 for the purpose of treating inflammatory diseases (when the immune system attacks the body's own tissues, resulting in inflammation) and fibrotic diseases (diseases caused by the thickening or scarring of tissue).Psoriasis is a chronic, relapsing inflammatory disease of the skin affecting approximately 1-3% of the world’s population. The most common form is plaque psoriasis representing 80-90% of all cases. Plaque psoriasis is defined by well-defined red, scaly plaques or patches which can occur anywhere on the body.
The immune system normally defends the body against harmful substances, diseases and infections. However, in people who have an autoimmune disease such as psoriasis, the immune system becomes overactive and attacks its own healthy cells.
S100A4 is a protein released in the body which can cause harm, contributing to over-activation of the immune system (inflammation) and tissue damage in diseases like psoriasis. AX-202 is a type of medication called a ‘monoclonal antibody’, which are antibodies designed to specifically bind to a disease-causing protein. AX-202 binds to and blocks the activity of S100A4, so may reduce inflammation and tissue damage in psoriasis.
This is the first study with AX-202 in humans and is designed to determine whether the drug is safe and well tolerated in healthy participants (Part A) and people with plaque psoriasis (Part B). The following will also be investigated:
• Pharmacokinetic blood analysis (levels of AX-202 in the body)
• Immunogenicity in blood (to see if the body is making antibodies against AX-202)
• Target engagement in blood and urine (interaction of AX-202 with its target protein ‘S100A4’)
• Biomarker analysis (which looks at specific biological features of the blood and skin)
• Disease activity in patients will be assessed using scoring systems (Part B only)Summary of Results
A total of 58 people (31 men and 27 women), aged 18–65 years, took part in the study:
• 41 healthy participants
• 17 participants with chronic plaque psoriasisAll doses of AX-202 (single doses of 0.5 mg/kg, 1.0 mg/kg, 3.0 mg/kg, 10.0 mg/kg and 20.0 mg/kg, and multiple doses of 10.0 mg/kg and 20.0 mg/kg [4 doses at 3-week intervals]) were safe and well tolerated, with no observed difference between the AX-202 and placebo dosing groups.
There was no correlation between the different dose levels administered, including the placebo, and the side effects reported after AX-202 was administered (known as Treatment emergent adverse events ‘TEAEs’).
One participant in the 20.0 mg/kg group in Part B experienced a mild infusion related reaction (a rash and numbness/tingling in the hands), which lead to discontinuation of the study treatment. This adverse event was considered related to study treatment by the study doctor. This participant received AX-202. Another participant experienced mild numbness/tingling in the hands, also considered related to study treatment by the study doctor but not leading to discontinuation of study treatment. This participant received placebo.
TEAEs reported by more than one participant are presented below.
Part A
Itchy rash from a dressing:
6 out of 30 participants (20%) receiving AX-202, 1 out of 10 participants (10%) receiving placebo (dummy drug with no active ingredient).
Swelling of the inside of the nose with symptoms such as runny nose, stuffiness, sneezing, itchy nose, and red, watery eyes (Rhinitis):
3 out of 30 participants (10%) receiving AX-202, 1 out of 10 participants (10%) receiving placebo.
Bruising at site of blood sampling:
2 out of 30 participants (7%) receiving AX-202, 1 out of 10 participants (10%) receiving placebo.
Headache:
2 out of 30 participants (7%) receiving AX-202, 1 out of 10 participants (10%) receiving placebo.
Diarrhoea:
1 out of 30 participants (3%) receiving AX-202, 2 out of 10 participants (20%) receiving placebo.
Part BSwelling of the inside of the nose with symptoms such as runny nose, stuffiness, sneezing, itchy nose, and red, watery eyes (Rhinitis):
5 out of 12 participants (42%) receiving AX-202, 2 out of 5 participants (40%) receiving placebo.
Itchy rash from a dressing:
3 out of 12 participants (25%) receiving AX-202, 1 out of 5 participants (20%) receiving placebo.
Headache:
2 out of 12 participants (17%) receiving AX-202, 2 out of 5 participants (40%) receiving placebo.
These TEAEs were not considered related to study treatment by the study doctor.Other results:
• Following single and multiple dosing of AX-202, pharmacokinetic data indicated that AX-202 was detectable in the blood in proportion to the dose given. The terminal half-life (the time it takes for the concentration of AX-202 to be reduced by 50%) was, on average, 3 weeks following repeated dosing of the higher doses.
• Results of the target engagement tests showed that AX-202 was successfully binding to the target protein ‘S100A4’.
• The levels of positive anti-drug antibodies observed in the immunogenicity testing were low, short lived and had no impact on AX-202 levels in the body or on participant safety.
• No consistent changes were seen in the exploratory biomarkers and clinical activity e.g. dermatology assessments, in participants with psoriasis (Part B) following administration of AX-202.The data from this study in healthy participants and participants with mild to moderate psoriasis supports further development of AX-202.
REC name
North West - Greater Manchester Central Research Ethics Committee
REC reference
22/NW/0333
Date of REC Opinion
2 Mar 2023
REC opinion
Further Information Favourable Opinion