Multiple sclerosisWednesday, June 11, 2008, 08:30 - 10:00Oral cladribine in relapsing-remitting multiple sclerosis: study design of the 2-year, Phase IIIb CLARITY (CLAdRIbine tablets Treating multiple sclerosis orallY) extension studyG. Giovannoni, S. Cook, S. Greenberg, P. Chang, G. Comi, P. Rieckmann, P. Soelberg Sørensen, P. Vermersch on behalf of the CLARITY (CLAdRIbine tablets Treating multiple sclerosis orallY) Study Group
Objectives: To investigate the long-term safety, tolerability and clinical benefit of oral cladribine tablets in patients with relapsing–remitting multiple sclerosis (RRMS).
Methods: Eligible patients from the 2-year CLARITY study will enter this Phase IIIb, double-blind, placebo-controlled, multicentre, parallel-group, 2-year extension study with a pre-study evaluation period, and two 1-year treatment periods. Randomization to the three treatment arms for the 2-year extension study will depend on the initial treatment allocated in the first 2 years of the CLARITY study: patients previously randomized to placebo will receive two courses per year of cladribine tablets throughout the 2-year extension trial; patients who previously received cladribine will be randomized (2:1) to receive two courses per year of cladribine tablets or placebo in their respective groups. Rescue treatment with interferon beta-1a (44 mcg subcutaneously three times weekly) or another disease-modifying drug will be available. The extension will be blinded for the 2-year study period.
Results: Primary analyses will be based on safety endpoints. These will include assessment of patients for at least one grade 4 CTCAE toxicity for measures of haematological and hepatic function; proportion of patients with grades 3 or 4 adverse events (AEs) for haematological or hepatic indices; incidence of all treatment-emergent AEs and serious AEs; incidence of infections, infection-related AEs and malignancies; time to recovery from haematological and liver toxicity; time to nadir of absolute lymphocyte count and time to recovery to normal values; and changes in QTc interval from baseline. Efficacy endpoints will include the proportion of relapse-free patients, relapse rates, and measures of disability progression at 1 and 2 years. Magnetic resonance imaging endpoints will include measures of: total burden of disease, transformation of T1 gadolinium (Gd)-enhancing lesions to hypointense lesions, brain volume changes, and new T1 Gd-enhancing and T2 lesions. Health-related quality of life, pharmacoeconomic and pharmacogenetic/genomic endpoints will also be assessed.
Conclusions: This study is designed to provide information on the long-term safety, tolerability and clinical benefit of extended administration of oral cladribine tablets for up to 4 years in patients with RRMS.
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