BACKGROUND: Cladribine is an oral immunomodulator that offers targeted, sustained effects on lymphocyte T and B subtypes. In the phase III 2-year CLARITY study, cladribine tablets demonstrated efficacy as a treatment for relapsing-remitting multiple sclerosis (MS) in an annual short-course oral dosing regimen. The cladribine safety registry will be established to collect safety information and will serve as an active surveillance system to better characterise the longterm safety profile of treatment with cladribine tablets.
METHODS: This is a subject registry study with a non-experimental cohort design. All subjects enrolled into a selected sponsor phase I-III clinical trial of the cladribine tablets development program (including those patients randomised to placebo) will be eligible for enrolment in the registry once their participation in the trial has ended. The duration of follow-up for all subjects will extend up to the end of the registry (preliminary estimate is mid-2018) or 8 years after enrolment into the first cladribine tablets clinical trial, whichever occurs first. Upon provision of informed consent by each subject, the principal registry physician will perform the registry enrolment assessment. During the first 2 years after enrolment, each subject will be interviewed every 3 months and thereafter, the contacts will occur every 6 months until the end of follow-up.
RESULTS: Approximately 2000 subjects will be enrolled in the cladribine tablets clinical development program and will be available for enrolment in the registry. It is estimated that 75% of these subjects will participate in the registry and that 500 sites will participate. Endpoints include the cumulative incidence of selected infections, malignancies, and deaths; dynamics of treatment-induced lymphocyte reduction; frequency of pregnancies and pregnancy outcomes occurring among female subjects exposed to cladribine, as well as among female partners of male subjects in the program.
CONCLUSIONS: This subject registry study provides a commitment to the long-term follow-up and safety surveillance of subjects who participated in sponsored cladribine clinical trials in MS, in order to build on existing knowledge about the safety profile of cladribine and to better support patient care.
