Challenge
The sponsor, Novartis Pharma AG, has developed a monoclonal antibody (secukinumab, a protein that specifically binds to another molecule), that selectively stops the effect of an endogenous protein called interleukin-17A (IL- 17A) and plays an role in many different types of inflammatory diseases such as psoriasis.
The study was designed to determine the concentration of the antibody and its effect on local inflammatory markers directly in the dermis by using dermal open flow microperfusion (dOFM).
Solution
After a single-dose, subcutaneous secukinumab injection, we measured antibody concentrations in skin (dOFM) and serum of healthy volunteers and psoriatic patients on day 8 and day 15. The concentrations of selected inflammatory markers in the skin and in serum were examined on days 1, 8 and 15. dOFM was used to measure IL-17 A concentrations and biomarkers for IL-17A expression (hBD-2) directly at the site of action.
Results
- A stable therapeutic concentration of the antibody was measured on day 8 and day 15 by using dOFM.
- We found increased levels of IL-17A in lesional skin relative to healthy skin.
- IL 17-A expression was decreased after secukinumab treatment of psoriatic lesions.
dOFM was found to be well-suited to detect PK and PD of a therapeutic antibody in healthy and lesional skin.
The details of the study were presented at several international conferences (e.g. AAPS National Biotechnology Conference 2014, Society for Investigative Dermatology 2014) and published in the papers below.
