CLARITY - Safety and Efficacy of Oral Cladribine in Subjects With Relapsing-Remitting MS

Condition(s) targeted: Multiple Sclerosis, Relapsing-Remitting

Intervention: Cladribine (Drug); Cladribine (Drug); Placebo (Other)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: EMD Serono

Official(s) and/or principal investigator(s):
Steven Greenberg, M.D., Study Director, Affiliation: EMD Serono, Inc.

The purpose of the study is to determine if cladribine is a safe and effective treatment for relapsing-remitting MS

Official title: A Phase III, Randomized, Double-Blind, Three-Arm, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Oral Cladribine in Subjects With Relapsing-Remitting Multiple Sclerosis

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: To evaluate the efficacy of cladribine versus placebo in the reduction of qualifying relapse rate during 96 weeks of treatment in subjects with RRMS.

Secondary outcome: To assess the effect of cladribine on progression of disability in subjects with RRMS

Detailed description: This will be a randomized, double-blind, three-arm, placebo-controlled, multi-center study. The study will include a pre-study evaluation period (up to 28 days prior to the start of treatment); an initial treatment period during Year 1; and a retreatment period during Year 2.

During the initial treatment period in Year 1, eligible subjects will be equally randomised by a central randomisation system to receive either a) cladribine at a low dose (0. 875 mg/kg/cycle for two cycles + placebo for two cycles); b) cladribine at a high dose (0. 875 mg/kg/cycle for four cycles); or c) placebo (four cycles). During the retreatment period in Year 2, subjects will receive either a) cladribine at a low dose (0. 875 mg/kg/cycle for two cycles); or b) placebo (two cycles).

For all randomized subjects, there will be a rescue option of treatment with Rebif (44 mcg three times a week (tiw)) if the subject experiences more than one qualifying relapse, and/or experiences a sustained increase in their EDSS of ³one point, or ³1. 5 points if baseline EDSS was 0, (over a period of three months or greater), during a calendar year beginning at Week 24.

To maintain the blind, there will be a Treating Physician who will view clinical laboratory results and assess AEs and safety information, and an independent blinded Evaluating Physician who will perform neurological exams. A central neuroradiology center, also blinded to treatment, will assess MRI evaluations.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 18 -65 years of age

- Definite MS according to the McDonald criteria

- Relapsing-remitting disease with 1 or more relapses within 12 months

- No relapse within 28 days

- MRI consistent with MS

- EDSS from 0-5. 5

- Weigh between 40-120 kg

- Males and females must use contraception

Exclusion Criteria:

- Pregnant or breast feeding

- Secondary Progressive MS (SPMS) or Primary Progressive MS (PPMS)

- Prior use of disease modifying drugs (DMDs) within the last 3 months, or 2 or more

prior treatment failures with DMDs

- Compromised immune function or infection, or prior use of medications that altered the

immune system

- Significant clinical or laboratory abnormalities at the screening visit (abnormal

platelet, neutrophil or white blood cell counts)

- Prior or current history of malignancy

- History of blood disorders after immunosuppressive therapy

- Systemic disease or psychiatric disorder that might interfere with subject safety,

compliance or evaluation of MS

- Use of any investigational drug or experimental procedure within 6 months

Local Medical Information Office, Geneva, Switzerland

Starting date: January 2005
Last updated: January 16, 2008