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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00213135
Recruitment Status : Completed
First Posted : September 21, 2005
Results First Posted : December 2, 2013
Last Update Posted : February 7, 2014
Sponsor:
Information provided by (Responsible Party):
EMD Serono

Tracking Information
First Submitted Date  ICMJE September 13, 2005
First Posted Date  ICMJE September 21, 2005
Results First Submitted Date  ICMJE September 30, 2013
Results First Posted Date  ICMJE December 2, 2013
Last Update Posted Date February 7, 2014
Study Start Date  ICMJE April 2005
Actual Primary Completion Date November 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2014)
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 Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 30, 2013)
  • 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 Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)
Official Title  ICMJE 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 (RRMS)
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 Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis, Relapsing-Remitting
Intervention  ICMJE
  • Drug: Cladribine 5.25 mg/kg
    Cladribine tablet will be administered as cumulative dose of 0.875 milligram per kilogram (mg/kg) over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the treatment period of 96 weeks.
  • Drug: Cladribine 3.5 mg/kg
    Cladribine tablet will be administered as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Weeks 1, 5, 48, and 52 and placebo matched to cladribine tablet will be administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.
  • Other: Placebo
    Placebo matched to cladribine tablet will be administered over a course of 4 or 5 consecutive days of 28-day period at Weeks 1, 5, 9, 13, 48 and 52 during the treatment period of 96 weeks.
Study Arms  ICMJE
  • Experimental: Cladribine 5.25 mg/kg
    Intervention: Drug: Cladribine 5.25 mg/kg
  • Experimental: Cladribine 3.5 mg/kg
    Intervention: Drug: Cladribine 3.5 mg/kg
  • Placebo Comparator: Placebo
    Intervention: Other: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 29, 2008)
1326
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE November 2008
Actual Primary Completion Date November 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female, between 18 and 65 years of age (inclusive, at time of informed consent)
  • Has definite MS according to the McDonald criteria
  • Has relapsing-remitting disease with 1 or more relapses within 12 months prior to Study Day 1
  • Must have been clinically stable and not has a relapse within 28 days prior to Study Day 1
  • Has MRI consistent with MS at the pre-study evaluation according to the Fazekas criteria
  • Has a EDSS score from 0 to 5.5, inclusive
  • Weighed between 40-120 kilogram (kg), inclusive
  • If female, she must:

    1. be post-menopausal or surgically sterilized; or
    2. uses a hormonal contraceptive, intra uterine device, diaphragm with spermicide, or condom with spermicide, for the duration of the study; and
    3. be neither pregnant nor breast-feeding
  • If male, he must be willing to use contraception to avoid pregnancies
  • Be willing and able to comply with study procedures for the duration of the study
  • Voluntarily provides written informed consent, and for United states of America (USA) sites only, a subject authorization under Health Insurance Portability and Accountability Act (HIPAA)

Exclusion Criteria:

  • Has 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 on the basis of efficacy
  • Has significant leukopenia (white blood cell count less than 0.5 times the lower limit of normal of the central laboratory) within 28 days prior to Study Day 1
  • Has received cladribine, mitoxantrone, total lymphoid irradiation, myelosuppressive therapy, campath-1h, cyclophosphamide, azathioprine, methotrexate or natalizumab
  • Has received oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days prior to Study Day 1
  • Has compromised immune function or infection
  • Has received oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days prior to Study Day 1
  • Has received cytokine-based therapy, intravenous immunoglobulin therapy, or plasmapheresis within 3 months prior to Study Day 1
  • Has platelet and absolute neutrophil counts below the lower limit of normal range within 28 days prior to Study Day 1
  • Has prior or current history of malignancy
  • Has a history of persistent anemia, leukopenia, neutropenia, or thrombocytopenia after immunosuppressive therapy
  • Has systemic disease that, in the opinion of the Investigator, might interfere with subject safety, compliance or evaluation of the condition under Study (for example, insulin-dependent diabetes, Lyme disease, clinically significant cardiac, hepatic, or renal disease, Human Immunodeficiency Virus, or Human T-Cell Lymphotrophic Virus Type-1)
  • Has a psychiatric disorder that, in the opinion of the Investigator, was unstable or would preclude safe participation in the study
  • Has allergy or hypersensitivity to gadolinium, to cladribine or any of its excipients
  • Has used any investigational drug or experimental procedure within 6 months prior to Study Day 1
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Canada,   Switzerland
 
Administrative Information
NCT Number  ICMJE NCT00213135
Other Study ID Numbers  ICMJE 25643
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party EMD Serono
Study Sponsor  ICMJE EMD Serono
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Steven J. Greenberg, M.D. EMD Serono
PRS Account EMD Serono
Verification Date January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP