Safety and Pharmacokinetics of JAK/ROCK Inhibitor in Healthy Volunteers
Condition: Healthy
Study type: Interventional
Phase: Phase 1

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 classified as
      a good clinical candidate for the treatment of RA.
    

Detailed description: 
      The following clinical trial consists of two phases IA and IB. Approximately 68 volunteers
      who meet all the inclusion and none of the exclusion criteria are going to be enrolled into
      the study. Phase IA (approx. 24 male and female volunteers) is to evaluate safety and
      tolerability after single oral administration of the Investigational Medicinal Produkt (IMP)
      to healthy volunteers. Additional cohort (approx 12 healthy volunteers) is going to be
      included in the phase IA of the study to assess the food effect on CPL409116 compound's
      bioavailability after one dose of single oral IMP administration. There are to be two
      treatments periods for this cohort: fasted and fed. Phase IB (approx. 32 male and female
      volunteers) is to evaluate safety and tolerability after two weeks of oral administration of
      IMP to healthy volunteers.
    

Intervention name(s): CPL409116; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): IMP administration, tablets contain CPL409116 as an active ingredient; Placebo comparator
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Pharmacokinetics; JAK inhibitors; ROCK inhibitors