Effect of Cladribine on lymphocytes and neuro-axonal damage

• Research type

  Research Study

• Full title

  Does Cladribine target CNS plasma cells and reduce neuro-axonal damage in people with MS (CLADRIPLAS)?

• IRAS ID

  240360

• Contact name

  Klaus Schmierer

• Contact email

  k.schmierer@qmul.ac.uk

• Sponsor organisation

  Queen Mary University of London

• Duration of Study in the UK

  2 years, 0 months, 0 days

• Research summary

  Multiple sclerosis (MS) is a chronic inflammatory demyelinating and degenerative disease of the central nervous system (CNS) with different clinical phenotypes. Whilst a number of disease modifying treatments (DMT) are licensed for early relapsing Multiple Sclerosis (RMS), many patients with later (progressive) MS remain without treatment. Cladribine is a synthetic purine analogue; oral preparation of which has recently been licensed for RMS in the EU and Canada. Earlier trials of Cladribine suggested efficacy in progressive MS too, however no licensed treatment has emerged from this.
  At our institution, The Royal London Hospital (Barts Health NHS Trust), we have been offering injectable (subcutaneous, s.c.) Cladribine as an off-label treatment for over three years to people with multiple sclerosis, particularly for patients with progressive MS not eligible for licensed DMT. In order to support the use of Cladribine in this population with mechanistic evidence, and with a view to undertaking a large scale trial, we will explore in this study the impact of Cladribine on validated biomarkers in the cerebro-spinal fluid and blood/serum.

  We will ask patients scheduled to be treated with Cladribine to have two lumbar punctures, at baseline and after 6 months of treatment, to detect products of plasma cells (free light chains, FLC) and oligo-clonal bands (OCB) both reflecting intrathecal inflammation; and neurofilament light chains (NfL) as a surrogate of neurodegeneration. We hypothesize that by targeting intrathecal plasma cells Cladribine reduces intrathecal FLC and OCB. If confirmed, this would support the use of Cladribine in people with progressive MS further.

• REC name

  North of Scotland Research Ethics Committee 1

• REC reference

  19/NS/0122

• Date of REC Opinion

  29 Jul 2019

• REC opinion

  Favourable Opinion