A Phase IIIB, Double Blind, Placebo-Controlled, Multcenter, Parallel Group, Extension Trial to Evaluate the Safety and Tolerability of Oral Cladribine in Subjects with Relapsing-Remitting Multiple Sclerosis Who Have Completed Trial 25643 (Clarity)

The trial will enrol eligible subjects with Relapsing remitting multiple
sclerosis who completed the two year Clarity study.
Patients wil be randomised and receive Placebo or oral Cladribine.

The objective of the study is to evaluate the safety of the extended treatment
with oral Cladribine and to determinate the effect on the QTc interval.
other objectives:
-explore the long term benefit (rate of disease progression as reflected by
rate of change in Expanded Disabiltiy Status Score) of treatment with oral
cladribine vs. placebo.
-explore the relationship between oral cladribine treatments and immunologic
parameters, MRI measurments of disease activities, clinical relapses and
disease progression in subjects previously randomised in trial 25643.
-detrminate the benefit of continued oral cladribine treatment on
health-related quality of life and economic outcome measures.
-explore the association between genetic variants, clinical efficacy, MRI
endpoints and groups of subjects with adverse events ( grade 3 and 4 toxicity).
- explore the effect of oral cladribine on gene expression profiles.

A phase IIIB, double-blind, placebo controlled, multicenter, parallel group,
extension of the Clarity study.

Study duration: 96 weeks.
19 study visits ( 1 screening visit, study day 1: to dispens treatment and 17
follow-up visits).
MRI scheduled at 5 visits. (study day 1, Week 24, 48, 72 and 96)
Blood and urine sampling at 19 visits.
If the patients consents: additional blood sampling for pharmacogenomics,
pharmacogenetics and PK analysis.
ECG scheduled at 5 visits
2 questionnaires: to be completed at 5 visits and in case of a relaps:
-Health related Quality of Life questionnaire
-Health Resource Utilazation questionnaire