11/25/23, 7:18 PM
`
`Study Details | A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS) | Cl…
`
`Go to the classic website
`
`The U.S. government does not review or approve the safety and science of all studies listed on this website.
`
`Read our full disclaimer (https://clinicaltrials.gov/about-site/disclaimer) for details.
`
`COMPLETED
`
`A Safety and E(cid:168)cacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple
`Sclerosis (RRMS) (CLARITY)
`
`ClinicalTrials.gov ID
`
`NCT00213135
`
`Sponsor
`
`EMD Serono
`
`Information provided by
`
`EMD Serono (Responsible Party)
`
`Last Update Posted
`
`2014-02-07
`
`Study Details Tab
`
`Study Overview
`
`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.
`
`O(cid:168)cial Title
`
`https://clinicaltrials.gov/study/NCT00213135
`
`Page 1 of 18
`
`Merck 2063
`TWi v Merck
`IPR2023-00050
`
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`
`

`

`Study Details | A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS) | Cl…
`11/25/23, 7:18 PM
`A Phase III, Randomized, Double-blind, Three-arm, Placebo-controlled, Multi-center Study to Evaluate the Safety and E(cid:168)cacy of Oral
`Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)
`Conditions
`
`Multiple Sclerosis, Relapsing-Remitting
`
`Intervention / Treatment
`
`Drug: Cladribine 5.25 mg/kg
`
`Drug: Cladribine 3.5 mg/kg
`
`Other: Placebo
`
`Other Study ID Numbers
`
`25643
`
`Study Start
`
`2005-04
`
`Primary Completion (Actual)
`
`2008-11
`
`Study Completion (Actual)
`
`2008-11
`
`Enrollment (Actual)
`
`1326
`
`Study Type
`
`Interventional
`
`Phase
`
`Phase 3
`
`Resource links provided by the National Library of Medicine
`
`MedlinePlus Genetics
`(https://medlineplus.gov/genetics/) related topics:(cid:193)
`(https://medlineplus.gov/genetics/condition/multiple-sclerosis)(cid:193)
`
`Multiple sclerosis
`
`MedlinePlus
`
`(https://medlineplus.gov/) related topics:(cid:193)
`
`Multiple Sclerosis
`
`(https://medlineplus.gov/multiplesclerosis.html)(cid:193)
`
`Drug Information
`(https://dailymed.nlm.nih.gov/dailymed/) available for:(cid:193)
`Cladribine
`(https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Cladribine)(cid:193)
`
`Other U.S. FDA Resources (https://classic.clinicaltrials.gov/ct2/info/fdalinks)
`
`Contacts and Locations
`https://clinicaltrials.gov/study/NCT00213135
`
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`Study Details | A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS) | Cl…
`11/25/23, 7:18 PM
`This section provides the contact details for those conducting the study, and information on where this study is being conducted.
`
`No location data
`
`Participation Criteria
`Researchers look for people who (cid:166)t a certain description, called eligibility criteria. Some examples of these criteria are a person's
`general health condition or prior treatments.
`
`For general information about clinical research, read Learn About Studies (https://clinicaltrials.gov/study-basics/learn-about-studies).
`
`https://clinicaltrials.gov/study/NCT00213135
`
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`Study Details | A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS) | Cl…
`
`Eligibility Criteria
`
`Description
`
`Inclusion Criteria:
`
`Male or female, between 18 and 65 years of age (inclusive, at time of informed consent)
`Has de(cid:166)nite 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 e(cid:168)cacy
`Has signi(cid:166)cant 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 signi(cid:166)cant cardiac, hepatic,
`or renal disease, Human Immunode(cid:166)ciency 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
`
`Ages Eligible for Study
`
`18 Years to 65 Years (Adult,(cid:193) Older Adult )
`
`Sexes Eligible for Study
`
`All
`
`Accepts Healthy Volunteers
`
`https://clinicaltrials.gov/study/NCT00213135
`
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`11/25/23, 7:18 PM
`No
`
`Study Details | A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS) | Cl…
`
`Study Plan
`This section provides details of the study plan, including how the study is designed and what the study is measuring.
`
`How is the study designed?
`
`Design Details
`
` : Treatment
`Primary Purpose
`Allocation
` : Randomized
`Interventional Model
` : Parallel Assignment
`Masking
` : Triple (Participant, Care Provider, Investigator)
`
`Arms and Interventions
`
`Participant Group/Arm
`
`Intervention/Treatment
`
`Experimental: Cladribine 5.25
`mg/kg
`
`Experimental: Cladribine 3.5
`mg/kg
`
`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.
`
`Placebo Comparator: Placebo
`
`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.
`
`What is the study measuring?
`
`https://clinicaltrials.gov/study/NCT00213135
`
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`
`Study Details | A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS) | Cl…
`
`Primary Outcome Measures
`
`Outcome Measure
`
`Measure Description
`
`Annualized Qualifying
`Relapse Rate
`
`A qualifying relapse was de(cid:166)ned 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 con(cid:166)rmed relapses divided by the total number
`of days on study multiplied by 365.25.
`
`Secondary Outcome Measures
`
`Outcome Measure
`
`Measure Description
`
`Percentage of Relapse-
`free Participants
`
`Time to Disability
`Progression
`
`A qualifying relapse was de(cid:166)ned 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 was de(cid:166)ned 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.
`
`Time Frame
`
`Week 96
`
`Time Frame
`
`Week 96
`
`Baseline up
`to Week 96
`
`Mean Number of
`Combined Unique (CU)
`Lesions, Active Time
`Constant 2 (T2)
`Lesions, and Active
`
`https://clinicaltrials.gov/study/NCT00213135
`
`Mean Number of CU lesions, active T2 lesions, and active T1 Gd+
`lesions were measured by using magnetic resonance imaging
`(MRI) scans.
`
`Week 96
`
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`

`Study Details | A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS) | Cl…
`11/25/23, 7:18 PM
`Time Constant 1 (T1)
`Gadolinium-Enhanced
`(Gd+) Lesions Per
`Participant Per Scan
`
`Collaborators and Investigators
`This is where you will (cid:166)nd people and organizations involved with this study.
`
`Sponsor
`
`EMD Serono
`
`Collaborators
`
`No information provided
`
`Investigators
`
`Study Director: Steven J. Greenberg, M.D., EMD Serono
`
`Publications
`The person responsible for entering information about the study voluntarily provides these publications. These may be about anything
`related to the study.
`
`General Publications
`
`No publications available
`
`* Find Publications about Study Results and related Pubmed Publications in the “Results” section of the study record.
`
`Study Record Dates
`These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported
`results are reviewed by the National Library of Medicine (NLM) to make sure they meet speci(cid:166)c quality control standards before being
`posted on the public website.
`
`Study Registration Dates
`
`First Submitted
`2005-09-13
`
`First Submitted that Met QC Criteria
`2005-09-13
`
`First Posted (Estimated)
`
`https://clinicaltrials.gov/study/NCT00213135
`
`Page 7 of 18
`
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`

`11/25/23, 7:18 PM
`2005-09-21
`
`Study Details | A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS) | Cl…
`
`Results Reporting Dates
`
`Results First Submitted
`2013-09-30
`
`Results First Submitted that Met QC Criteria
`
`2013-09-30
`
`Results First Posted (Estimated)
`2013-12-02
`
`Study Record Updates
`
`Last Update Submitted that met QC Criteria
`
`2014-01-10
`
`Last Update Posted (Estimated)
`2014-02-07
`
`Last Veri(cid:166)ed
`2014-01
`
`More Information
`
`Terms related to this study
`
`Additional Relevant MeSH Terms
`
`Pathologic Processes
`Demyelinating Autoimmune Diseases, CNS
`Autoimmune Diseases of the Nervous System
`Nervous System Diseases
`Demyelinating Diseases
`Autoimmune Diseases
`Immune System Diseases
`Multiple Sclerosis
`Multiple Sclerosis, Relapsing-Remitting
`Sclerosis
`Antineoplastic Agents
`Immunosuppressive Agents
`Immunologic Factors
`Physiological Effects of Drugs
`Cladribine
`
`Study Documents
`
`https://clinicaltrials.gov/study/NCT00213135
`
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`
`Study Details | A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS) | Cl…
`
`No study documents available
`
`https://clinicaltrials.gov/study/NCT00213135
`
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`

`11/25/23, 7:49 PM
`
`Record History | ver. 13: 2008-01-16 | NCT00213135 | ClinicalTrials.gov
`
`Go to the classic website
`
`The U.S. government does not review or approve the safety and science of all studies listed on this website.
`
`Read our full disclaimer (https://clinicaltrials.gov/about-site/disclaimer) for details.
`
`COMPLETED
`
`A Safety and E(cid:168)cacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple
`Sclerosis (RRMS) (CLARITY)
`
`ClinicalTrials.gov ID
`
`NCT00213135
`
`Sponsor
`
`EMD Serono
`
`Information provided by
`
`EMD Serono (Responsible Party)
`
`Last Update Posted
`
`2014-02-07
`
`Record History Tab
`
`Study Record Versions
`This table shows the list of all the versions of this study record arranged in order by date.
`The (cid:166)rst column shows the date the study record was updated, and the second column shows the elements in the study record that
`were changed.
`To view a version of a study record, click the version date.
`To compare versions, select two versions using the check boxes and click the "Compare" button at the bottom of the list.
`
`2005-09-13
`
`None (earliest version on record)
`
`2005-11-15
`
`2006-02-02
`
`Study Status
`Study Identi(cid:166)cation
`
`Study Status
`Contacts/Locations
`
`2006-03-22
`
`Study Status
`
`2006-05-17
`
`2006-08-01
`
`Study Status
`Study Identi(cid:166)cation
`
`Study Status
`Contacts/Locations
`
`2006-08-31
`
`Study Status
`
`https://clinicaltrials.gov/study/NCT00213135?tab=history&a=13
`
`Compare
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`
`Record History | ver. 13: 2008-01-16 | NCT00213135 | ClinicalTrials.gov
`
`2006-10-05
`
`2006-12-06
`
`2007-04-10
`
`2007-04-13
`
`2007-05-29
`
`2008-01-16
`
`Outcome Measures
`Study Identi(cid:166)cation
`Study Design
`
`Study Status
`Contacts/Locations
`
`Recruitment Status
`Study Status
`
`Study Status
`Outcome Measures
`Contacts/Locations
`
`Study Status
`Study Design
`Outcome Measures
`
`Study Status
`Conditions
`Study Design
`Outcome Measures
`
`Study Status
`Study Identi(cid:166)cation
`Study Description
`Conditions
`Study Design
`Arms and Interventions
`Eligibility
`Contacts/Locations
`Sponsor/Collaborators
`
`2008-09-29
`
`Study Status
`Study Design
`
`2009-03-21
`
`Study Status
`
`2009-12-11
`
`Recruitment Status
`Study Identi(cid:166)cation
`Study Status
`Arms and Interventions
`Contacts/Locations
`Sponsor/Collaborators
`
`2011-08-05
`
`Study Status
`References
`
`https://clinicaltrials.gov/study/NCT00213135?tab=history&a=13
`
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`
`Record History | ver. 13: 2008-01-16 | NCT00213135 | ClinicalTrials.gov
`
`Study Identi(cid:166)cation
`Study Description
`Arms and Interventions
`Eligibility
`
`Study Status
`Sponsor/Collaborators
`
`Study Status
`Outcome Measures
`Baseline Characteristics
`Study Identi(cid:166)cation
`Study Description
`Arms and Interventions
`Eligibility
`Participant Flow
`Adverse Events
`More Information
`
`Study Status
`Outcome Measures
`Baseline Characteristics
`
`2012-01-27
`
`2013-09-30
`
`2014-01-10
`
`Date
`
`Changes
`
`Study Details
`
`Version 13: 2008-01-16
`
`Study Identi(cid:166)cation
`
`Unique Protocol ID
`
`25643
`
`Brief Title
`
`CLARITY - Safety and E(cid:168)cacy of Oral Cladribine in Subjects With Relapsing-Remitting MS
`
`O(cid:168)cial Title
`
`A Phase III, Randomized, Double-Blind, Three-Arm, Placebo-Controlled, Multi-Center Study to
`Evaluate the Safety and E(cid:168)cacy of Oral Cladribine in Subjects With Relapsing-Remitting
`Multiple Sclerosis
`Changes
`Secondary IDs
`
`Date
`
`https://clinicaltrials.gov/study/NCT00213135?tab=history&a=13
`
`Page 12 of 18
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`

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`
`Record History | ver. 13: 2008-01-16 | NCT00213135 | ClinicalTrials.gov
`
`Study Status
`
`Record Veri(cid:166)cation
`
`2008-01
`
`Overall Status
`
`Active, not recruiting
`
`Study Start
`
`2005-01
`
`Primary Completion
`
`2008-12 [Estimated]
`
`Study Completion
`
`First Submitted
`
`2005-09-13
`
`First Submitted that Met QC Criteria
`
`2005-09-13
`
`First Posted
`
`2005-09-21
`
`Last Update Submitted that Met QC Criteria
`
`2008-01-16
`
`Last Update Posted
`
`2008-01-17 [Estimated]
`
`Sponsor/Collaborator
`
`Sponsor
`
`EMD Serono
`
`Responsible Party
`
`Collaborators
`
`Date
`
`Oversight
`Changes
`
`U.S. FDA-regulated Drug
`
`https://clinicaltrials.gov/study/NCT00213135?tab=history&a=13
`
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`
`Record History | ver. 13: 2008-01-16 | NCT00213135 | ClinicalTrials.gov
`
`U.S. FDA-regulated Device
`
`Data Monitoring
`
`Study Description
`
`Brief Summary
`
`The purpose of the study is to determine if cladribine is a safe and effective treatment for
`relapsing-remitting MS
`
`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.
`
`Conditions
`
`Condition
`
`Multiple Sclerosis, Relapsing-Remitting
`
`Keywords
`
`Study Design
`
`Study Type
`
`Interventional
`
`https://clinicaltrials.gov/study/NCT00213135?tab=history&a=13
`
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`
`Record History | ver. 13: 2008-01-16 | NCT00213135 | ClinicalTrials.gov
`
`Assigned Interventions
`
`Drug: Cladribine
`
`Cladribine low dose (0.875
`mg/kg/cycle)
`
`Primary Purpose
`
`Treatment
`
`Study Phase
`
`Phase 3
`
`Interventional Study Model
`
`Parallel Assignment
`
`Interventional Model Description
`
`Number of Arms
`
`3 M
`
`asking
`
`Triple (Participant, Care Provider, Investigator)
`
`Masking Description
`
`Allocation
`
`Randomized
`
`Enrollment
`
`1290 [Actual]
`
`Arms and Interventions
`
`Arms
`
`Experimental: 1
`
`Experimental: 2
`
`Drug: Cladribine
`
`Cladribine high dose (0.875
`mg/kg/cycle)
`
`Placebo Comparator: 3
`
`Other: Placebo
`
`Placebo
`
`Outcome Measures
`
`https://clinicaltrials.gov/study/NCT00213135?tab=history&a=13
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`Record History | ver. 13: 2008-01-16 | NCT00213135 | ClinicalTrials.gov
`
`Primary Outcome Measures
`
`1. To evaluate the e(cid:168)cacy of cladribine versus placebo in the reduction of qualifying relapse
`rate during 96 weeks of treatment in subjects with RRMS.
`[Time Frame: During 96 weeks]
`
`Secondary Outcome Measures
`
`1. To assess the effect of cladribine on progression of disability in subjects with RRMS
`[Time Frame: At 96 weeks]
`
`Eligibility
`
`Minimum Age
`
`18 Years
`
`Maximum Age
`
`65 Years
`
`Sex
`
`All
`
`Accepts Healthy Volunteers
`
`No
`
`Criteria
`
`Inclusion Criteria:
`
`18 -65 years of age
`De(cid:166)nite 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
`Signi(cid:166)cant 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
`
`Contacts/Locations
`
`https://clinicaltrials.gov/study/NCT00213135?tab=history&a=13
`
`Central Contact Person
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`Record History | ver. 13: 2008-01-16 | NCT00213135 | ClinicalTrials.gov
`
`Study O(cid:168)cials
`
`Name
`Steven Greenberg, M.D.
`Role
`Study Director
`
`A(cid:168)liation
`EMD Serono
`
`Location
`
`Geneva, Switzerland
`Facility:
`Local Medical Information O(cid:168)ce
`
`IPD Sharing
`
`Available IPD/Information
`
`IPD information
`
`References
`
`Citations
`
`Stefano N, Sormani MP, Giovannoni G, Rammohan K, Leist TP, Coyle PK,
`Dangond F, Alexandri N, Galazka A. Relapses in people with multiple sclerosis
`treated with cladribine tablets followed for up to 5 years: a plain language
`summary. Neurodegener Dis Manag. 2022 Dec;12(6):303-310. doi:
`10.2217/nmt-2022-0019. Epub 2022 Aug 26.
`
`(https://p
`ubmed.nc
`bi.nlm.nih.
`gov/3601
`7797)
`
`Giovannoni G, Comi G, Rammohan K, Rieckmann P, Dangond F, Jack D,
`Vermersch P. Disease stability over (cid:166)ve years in people with multiple
`sclerosis treated with cladribine tablets: a plain language summary.
`Neurodegener Dis Manag. 2022 Dec;12(6):295-301. doi: 10.2217/nmt-2022-
`0018. Epub 2022 Aug 26.
`
`(https://pu
`bmed.ncbi.
`nlm.nih.go
`v/3601778
`0)
`
`Vermersch P, Galazka A, Dangond F, Damian D, Wong SL, Jack D, Harty G.
`The effect of cladribine tablets in people with more active multiple
`sclerosis: a plain language summary. Neurodegener Dis Manag. 2022
`Dec;12(6):285-293. doi: 10.2217/nmt-2022-0009. Epub 2022 Aug 3.
`
`(https://pub
`med.ncbi.nl
`m.nih.gov/3
`5920065)
`
`Oh J, Walker B, Giovannoni G, Jack D, Dangond F, Nolting A, Aldridge J,
`Lebson LA, Leist TP. Side effects that occurred early in people with multiple
`sclerosis during the (cid:166)rst year of treatment with cladribine tablets: a plain
`language summary. Neurodegener Dis Manag. 2022 Feb 1;12(1):1-7. doi:
`10.2217/nmt-2021-0041. Epub 2022 Jan 12.
`
`(https://p
`ubmed.nc
`bi.nlm.nih.
`gov/3501
`9731)
`
`Giovannoni G, Coyle PK, Vermersch P, Walker B, Aldridge J, Nolting A,
`Galazka A, Lemieux C, Leist TP. Integrated Lymphopenia Analysis in Younger
`and Older Patients With Multiple Sclerosis Treated With Cladribine Tablets.
`Front Immunol. 2021 Dec 24;12:763433. doi: 10.3389/(cid:166)mmu.2021.763433.
`eCollection 2021.
`
`(https://pu
`bmed.ncbi
`.nlm.nih.g
`ov/350030
`76)
`
`Giovannoni G, Comi G, Rammohan K, Rieckmann P, Dangond F, Keller B, Jack D,
`Vermersch P. Long-Term Disease Stability Assessed by the Expanded Disability
`Status Scale in Patients Treated with Cladribine Tablets 3.5 mg/kg for
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`
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`pubmed
`.ncbi.nl
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`Record History | ver. 13: 2008-01-16 | NCT00213135 | ClinicalTrials.gov
`Relapsing Multiple Sclerosis: An Exploratory Post Hoc Analysis of the CLARITY
`and CLARITY Extension Studies. Adv Ther. 2021 Sep;38(9):4975-4985. doi:
`10.1007/s12325-021-01865-w. Epub 2021 Aug 9.
`De Stefano N, Sormani MP, Giovannoni G, Rammohan K, Leist T, Coyle PK,
`Dangond F, Keller B, Alexandri N, Galazka A. Analysis of frequency and severity
`of relapses in multiple sclerosis patients treated with cladribine tablets or
`placebo: The CLARITY and CLARITY Extension studies. Mult Scler. 2022
`Jan;28(1):111-120. doi: 10.1177/13524585211010294. Epub 2021 May 10.
`
`m.nih.g
`ov/343
`70275)
`(https://p
`ubmed.n
`cbi.nlm.n
`ih.gov/33
`969750)
`
`Giovannoni G, Galazka A, Schick R, Leist T, Comi G, Montalban X, Damian D,
`Dangond F, Cook S. Pregnancy Outcomes During the Clinical Development
`Program of Cladribine in Multiple Sclerosis: An Integrated Analysis of Safety.
`Drug Saf. 2020 Jul;43(7):635-643. doi: 10.1007/s40264-020-00948-x.
`
`Terranova N, Hicking C, Dangond F, Munafo A. Effects of Postponing
`Treatment in the Second Year of Cladribine Administration: Clinical Trial
`Simulation Analysis of Absolute Lymphocyte Counts and Relapse Rate in
`Patients with Relapsing-Remitting Multiple Sclerosis. Clin Pharmacokinet.
`2019 Mar;58(3):325-333. doi: 10.1007/s40262-018-0693-y.
`
`(https://pu
`bmed.ncbi.
`nlm.nih.gov
`/32447743
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`
`(https://p
`ubmed.nc
`bi.nlm.nih
`.gov/299
`92396)
`
`Afolabi D, Albor C, Zalewski L, Altmann DR, Baker D, Schmierer K. Positive
`impact of cladribine on quality of life in people with relapsing multiple
`sclerosis. Mult Scler. 2018 Oct;24(11):1461-1468. doi:
`10.1177/1352458517726380. Epub 2017 Aug 17.
`
`(https://pub
`med.ncbi.nl
`m.nih.gov/28
`817997)
`
`Savic RM, Novakovic AM, Ekblom M, Munafo A, Karlsson MO. Population
`Pharmacokinetics of Cladribine in Patients with Multiple Sclerosis. Clin
`Pharmacokinet. 2017 Oct;56(10):1245-1253. doi: 10.1007/s40262-017-
`0516-6.
`
`(https://pubm
`ed.ncbi.nlm.ni
`h.gov/282558
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`
`De Stefano N, Giorgio A, Battaglini M, De Leucio A, Hicking C, Dangond F,
`Giovannoni G, Sormani MP. Reduced brain atrophy rates are associated with
`lower risk of disability progression in patients with relapsing multiple
`sclerosis treated with cladribine tablets. Mult Scler. 2018 Feb;24(2):222-226.
`doi: 10.1177/1352458517690269. Epub 2017 Jan 31.
`
`(https://p
`ubmed.nc
`bi.nlm.nih
`.gov/281
`40753)
`
`Ali S, Paracha N, Cook S, Giovannoni G, Comi G, Rammohan K, Rieckmann P,
`Sorensen PS, Vermersch P, Greenberg S, Scott DA, Joyeux A; CLARITY
`(CLAdRIbine Tablets treating multiple sclerosis orallY) Study Group. Reduction in
`healthcare and societal resource utilization associated with cladribine tablets in
`patients with relapsing-remitting multiple sclerosis: analysis of economic data
`from the CLARITY Study. Clin Drug Investig. 2012 Jan 1;32(1):15-27. doi:
`10.2165/11593310-000000000-00000.
`
`(https:
`//pub
`med.n
`cbi.nl
`m.nih.
`gov/22
`01751
`9)
`
`Giovannoni G, Comi G, Cook S, Rammohan K, Rieckmann P, Soelberg
`Sorensen P, Vermersch P, Chang P, Hamlett A, Musch B, Greenberg SJ;
`CLARITY Study Group. A placebo-controlled trial of oral cladribine for
`relapsing multiple sclerosis. N Engl J Med. 2010 Feb 4;362(5):416-26. doi:
`10.1056/NEJMoa0902533. Epub 2010 Jan 20.
`
`(https://pu
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`960)
`
`Links
`
`Document Section
`
`https://clinicaltrials.gov/study/NCT00213135?tab=history&a=13
`
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