Cladribine tablets after treatment with natalizumab (CLADRINA) - rationale and design

Peter V Sguigna; Rehana Z Hussain; Annette Okai; Kyle M Blackburn; Lauren Tardo; Mariam Madinawala; Julie Korich; Lori A Lebson; Jeffrey Kaplan; Amber Salter; Navid Manouchehri; Olaf Stuve

doi:10.1177/17562864241233858

Cladribine tablets after treatment with natalizumab (CLADRINA) - rationale and design

Ther Adv Neurol Disord. 2024 Apr 4:17:17562864241233858. doi: 10.1177/17562864241233858. eCollection 2024.

Authors

Affiliations

¹ Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
² North Texas Institute of Neurology & Headache, Plano, TX, USA.
³ EMD Serono, Inc., Rockland, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany.
⁴ Kansas City Multiple Sclerosis and Headache Center, Overland Park, KS, USA.
⁵ Department of Neurology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX 75390-8813, USA.
⁶ Neurology Section, VA North Texas Health Care System, Dallas, TX, USA.

Abstract

Background: Individual disease modifying therapies approved for multiple sclerosis (MS) have limited effectiveness and potentially serious side effects, especially when administered over long periods. Sequential combination therapy is a plausible alternative approach. Natalizumab is a monoclonal therapeutic antibody that reduces leukocyte access to the central nervous system that is associated with an increased risk of progressive multifocal leukoencephalopathy and disease reactivation after its discontinuation. Cladribine tablets act as a synthetic adenosine analog, disrupting DNA synthesis and repair, thereby reducing the number of lymphocytes. The generation of prospective, rigorous safety, and efficacy data in transitioning from natalizumab to cladribine is an unmet clinical need.

Objectives: To test the feasibility of transitioning patients with relapsing forms of MS natalizumab to cladribine tablets.

Design: Cladribine tablets after treatment with natalizumab (CLADRINA) is an open-label, single-arm, multicenter, collaborative phase IV, research study that will generate hypothesis regarding the safety, efficacy, and immunological impact of transition from natalizumab to cladribine tablets in patients with relapsing forms of MS.

Methods and analysis: Participants will be recruited from three different sites. The primary endpoint is the absolute and percent change from baseline of lymphocytes and myeloid cell subsets, as well as blood neurofilament light levels. The secondary endpoint is the annualized relapse rate over the 12- and 24-month trial periods. Exploratory endpoints include the expanded disability status scale, and magnetic resonance imaging outcomes.

Discussion: The CLADRINA trial will generate data regarding the safety, efficacy, and immunological impact of the transition from natalizumab to cladribine. As the pace of immunological knowledge of MS continues, insight into disease modifying therapy transition strategies is needed.

Keywords: cladribine tablets; multiple sclerosis; natalizumab; neurofilament light chain; progressive multifocal leukoencephalopathy.