Safety and Tolerability of Cladribine Tablets in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS): Final Results from the 120-Week Phase IIIb Extension Trial to the CLARITY Study (P3.095)

Objective: To investigate safety (particularly, lymphocyte levels) and tolerability in RRMS patients in the 2-year CLARITY study and followed for 2.5 additional years on cladribine or placebo. Background: In CLARITY, cladribine tablets significantly reduced relapse rates, disability progression and MRI measures of disease activity over 2 Consistent with cladribine’s mechanism of action, the most commonly reported adverse event (AE) was lymphopenia. who completed CLARITY entered a 2-year Extension (following a median gap of 40 weeks); those who completed CLARITY-Extension underwent safety monitoring for a further 6 months. Safety and tolerability outcomes were reported after 2 and 2.5 years. Methods: Patients who completed treatment in CLARITY were eligible for treatment in the Extension. Placebo-recipients in CLARITY received cladribine 3.5 mg/kg of body weight, while cladribine recipients (from the original 3.5 mg/kg or 5.25 mg/kg arms) were re-randomized 2:1 to cladribine 3.5 mg/kg or placebo for 2 years (5 groups in total). Results: 89 (11.0[percnt]) patients discontinued treatment due to AEs. who transitioned from cladribine treatment to placebo during the Extension had fewer AE-related treatment discontinuations than those who continued on cladribine tablets. The incidences of lymphopenia and grade-3/4 lymphopenia were greatest in the groups receiving cladribine tablets in both CLARITY and the Extension; Approximately 6[percnt] of patients receiving placebo in the Extension had a grade-3/4 lymphopenia. Most AEs were mild or moderate. The most common serious AEs in all groups were infections, gastrointestinal disorders and malignancies/unspecified tumours. Deaths (n=3) were considered unrelated/unlikely to be related to treatment. Conclusions: Overall, safety and tolerability in CLARITY Extension were consistent with that seen in CLARITY.Study supported by: Merck KGaA Darmstadt, Germany. Disclosure: Dr. Cook has received personal compensation for activities with Merck Serono, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, Teva Pharmaceuticals, and Actinobac Biomed Inc. Dr. Comi has received personal compensation for activities with Teva, Novartis, Genzyme, Merck Serono, Biogen, Bayer, Actelion, Almirall, and Serono Symposia International Foundation. Dr. Rammohan has received personal compensation for activities with EMD Serono, Biogen Idec, Sanofi-Aventis, Genzyme Corporation, Novartis, Teva Neurosciences, Acorda and Roche/Genentech Inc. as a speaker and committee member. Dr. Soelberg-Sorensen has received personal compensation for activities with Biogen Idec, Merck Serono, Novartis, Genmab, Teva, Elan, and GlaxoSmithKline, Inc. Dr. Vermersch has received personal compensation for activities with Biogen Idec, Sanofi, Bayer, Novartis, Merck Serono, GlaxoSmithKline, and Almirall. Dr. Vermersch has received research support from Biogen Idec, Sanofi, Bayer, and Merck Serono. Dr. Martin has received personal compensation for activities with EMD Serono, Inc. as an employee. Dr. Dangond has received personal compensation for activities with EMD Serono, Inc. as an employee. Dr. Giovannoni has received personal compensation for activities with AbbVie Biotherapeutics Inc., Biogen, Bayer HealthCare, Genzyme, Merck Serono, Sanofi-Aventis, Teva, Ironwood, and Novartis. Dr. Giovannoni has received personal compensation for activities with Bayer Schering Pharma, FivePrime, GlaxoSmithKline, GW Pharma, Merck Serono, Biogen Idec, Pfizer Inc, and Protein Discovery Laboratories.