Safety and Pharmacokinetics of JAK/ROCK Inhibitor in Healthy Volunteers
Status:
Recruiting
Trial end date:
2021-08-31
Target enrollment:
Participant gender:
Summary
The aim of the following clinical trial is to determine safety an pharmacokinetic parameters
in healthy volunteers after oral administration of Janus kinases and Rho-kinases inhibitor
(JAK/ROCKi), called CPL409116.Janus kinase (JAK) inhibitors are a new class of small molecule
drugs that modulate inflammatory pathways by blocking one or more JAK receptors. In recent
years, JAK inhibitors have emerged as a new option for the treatment of various inflammatory
diseases, including rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, skin
disorders and others. CPL409116 inhibits JAK1 and JAK3 with less inhibitory activity against
JAK2 and Tyk2. Inhibition of these kinases decreases inflammatory cytokine release which in
turn decreases lymphocyte activation and proliferation. Moreover, CPL409116 blocks
Rho-kinases (ROCKs), which are involved in diverse cellular processes including actin
cytoskeleton organization, cell adhesion and motility, proliferation, apoptosis as well as
smooth muscle contraction. ROCKs signalling is one of the major pathways implicated in the
pathogenesis of cardiovascular, renal as well as fibrotic diseases. However recent data
indicate their role in immune cell regulation and inflammatory disease development. CPL409116
was designed predominantly for the therapy of immune-related diseases: rheumatoid arthritis,
psoriasis and because antifibrotic therapies are needed. Dual inhibition of JAK/ROCK kinases
may be beneficial for patients suffering from fibrotic complications of inflammatory disease.
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterised by
persistent joint inflammation leading to loss of joint function as well as cartilage and bone
damage. Chronic, progressive course of the disease results in disability, reduced quality of
life, as well as higher comorbidity and mortality rates. It is well documented that JAK
kinases play a pivotal role in cytokine receptor signalling to phosphorylate and activate
signal transducer and activator of transcription (STAT) proteins. Several of these
JAK-controlled cytokine receptor pathways are immediately involved in the initiation and
progression of RA pathogenesis. Cytokines promote autoimmunity, maintain chronic inflammatory
synovitis and drive the destruction of joint tissue. In consequence on the basis of the
preclinical study results the IMP with the active ingredient CPL409116 has been qualified as
a good clinical candidate for the treatment of RA.
Phase:
Phase 1
Details
Lead Sponsor:
Celon Pharma SA
Collaborator:
National Center for Research and Development, Poland