Cladribine Tablets after Treatment with Natalizumab (CLADRINA) Trial – Interim Analyses

Background: Natalizumab is a highly effective disease-modifying therapy for patients with relapsing forms of multiple sclerosis (MS) that is associated with an increased risk of disease reactivation after cessation of dosing. Outcomes following early initiation of another highly effective therapy, cladribine tablets, after stopping natalizumab have not yet been fully explored.

Objectives: The purpose of this study is to generate hypotheses regarding the safety, efficacy, and immunological impact of cladribine tablets after switching from natalizumab in patients with relapsing-remitting MS (RRMS) or active secondary progressive MS (SPMS).

Methods: CLADRINA is an open-label, single-arm, multicenter, collaborative Phase 4 research study. A total of 40 study participants with RRMS or active SPMS who meet the criteria for treatment with cladribine tablets as per the approved United States Prescribing Information (USPI), are planned to be enrolled at up to three centers in the US. All study participants will receive treatment with cladribine tablets 3.5 mg/kg cumulative dose over 2 years according to the approved USPI (EMD Serono, 2019). Treatment with cladribine tablets will be initiated approximately 14 days after the last infusion of natalizumab. The primary endpoint is absolute and percent change from baseline for CD3⁺ T lymphocytes, CD19⁺ B lymphocytes, CD11c⁺ dendritic cell subsets, and neurofilament light chain levels in blood at 6, 9, 12, and 24 months. The secondary endpoint is annualized relapse rate over 12 and 24 months. Exploratory endpoints include mean number of T1 gadolinium-enhancing (Gd+) lesions and new or enlarging T2 lesions on magnetic resonance imaging (MRI) at Months 12 and 24.

Results: Twenty patients with MS have been enrolled to date; 18 of 20 have passed 6 months of treatment. There were no new T1 Gd+ lesions or new or enlarging T2 lesions on brain MRI after starting cladribine tablets. One patient had a clinical relapse associated with contrast-enhancing new lesions in the cervical spine on the day treatment was initiated. No study medication-related adverse events have been reported.

Conclusions: This interim analysis suggests that starting treatment with cladribine tablets approximately 14 days after the last infusion of natalizumab was not associated with new MS-related activity or adverse events in the first 6 months of treatment. A single relapse in our study cohort on the day of treatment initiation is unlikely to be causally related to cladribine tablets.