Clinical Trial: A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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-remitti

Brief Summary: The purpose of the study is to determine if cladribine tablets are a safe and effective treatment for relapsing-remitting multiple sclerosis (RRMS).

Detailed Summary:

This is a randomized, double-blind, three-arm, placebo-controlled, multi-center study. The study includes a pre-study evaluation period (up to 28 days prior to the start of treatment); an initial treatment period from Week 1 to 48; and a re-treatment period during Week 49 to 96.

During the initial treatment period (Week 1 to 48), eligible subjects are equally randomized by a central randomization system to receive either a) cladribine at a low dose (0.875 milligram per kilogram per course [mg/kg/course] for two courses plus placebo for two courses); b) cladribine at a high dose (0.875 mg/kg/course for four courses); or c) placebo (four courses). During the re-treatment period (Weeks 49 to 96), subjects received either a) cladribine at a low dose (0.875 mg/kg/course for two courses); or b) placebo (two courses).

For all randomized subjects, there is a rescue option of treatment with Rebif® (interferon beta-1a 44 microgram (mcg) given subcutaneously three times a week), if the subject experienced more than one qualifying relapse, and/or experienced a sustained increase in their EDSS score of greater than or equal to (>=) 1 point, or >=1.5 points if baseline EDSS score is 0, (over a period of three months or greater), during a calendar year beginning at Week 24.

To maintain the blind, there is a treating physician who view clinical laboratory results and assess adverse events and safety information, and an independent blinded evaluating physician who will perform neurological exams. A central neuroradiology center, also blinded to treatment, will assess magnetic resonance imaging (MRI) evaluations.


Sponsor: EMD Serono

Current Primary Outcome: Annualized Qualifying Relapse Rate [ Time Frame: Week 96 ]

A qualifying relapse was defined as an increase of 2 points in at least one functional system of the expanded disability status scale (EDSS) or an increase of 1 point in at least two functional systems (excluding changes in bowel or bladder function or cognition) in the absence of fever, lasting for at least 24 hours and to have been preceded by at least 30 days of clinical stability or improvement. Expanded disability status scale (EDSS) assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis [MS]) was calculated. The annualized relapse rate for each treatment group was calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25.


Original Primary Outcome:

Current Secondary Outcome:

  • Percentage of Relapse-free Participants [ Time Frame: Week 96 ]
    A qualifying relapse was defined as an increase of 2 points in at least one functional system of the EDSS or an increase of 1 point in at least two functional systems (excluding changes in bowel or bladder function or cognition) in the absence of fever, lasting for at least 24 hours and to have been preceded by at least 30 days of clinical stability or improvement. Expanded disability status scale (EDSS) assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated.
  • Time to Disability Progression [ Time Frame: Baseline up to Week 96 ]
    Time to disability progression was defined as the time to a sustained increase in EDSS score of at least 1 point if baseline EDSS score between 0.5 and 4.5 inclusively, or at least 1.5 points if the baseline EDSS score was 0, or at least 0.5 point if the baseline EDSS score was at least 5, over a period of at least three months. Expanded disability status scale (EDSS) assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Tenth Percentile of time to sustained increase in EDSS score was reported using Kaplan-Meier survival curve.
  • Mean Number of Combined Unique (CU) Lesions, Active Time Constant 2 (T2) Lesions, and Active Time Constant 1 (T1) Gadolinium-Enhanced (Gd+) Lesions Per Participant Per Scan [ Time Frame: Week 96 ]
    Mean Number of CU lesions, active T2 lesions, and active T1 Gd+ lesions were measured by using magnetic resonance imaging (MRI) scans.


Original Secondary Outcome:

Information By: EMD Serono

Dates:
Date Received: September 13, 2005
Date Started: April 2005
Date Completion:
Last Updated: January 10, 2014
Last Verified: January 2014