Multiple Sclerosis
Conditions
Keywords
Clinically Isolated Syndrome (CIS), Early MS, Multiple Sclerosis
Brief summary
A randomized, double-blind, clinical trial to assess the safety and efficacy of two doses of oral cladribine versus placebo in participants who had a first clinical demyelinating event (clinically isolated syndrome). Participants in either the cladribine or placebo group may also enter treatment periods with open-label interferon-beta or open-label cladribine depending upon the disease status. The primary objective of this study is to evaluate the effect of two dosage regimens of oral cladribine versus placebo on the time to conversion to multiple sclerosis (MS) (from randomization) according to the Poser criteria in participants with first clinical demyelinating event at high risk of converting to MS.
Detailed description
This will be a randomized, double blind, three-arm, placebo-controlled, multi-center trial to evaluate the safety and efficacy of oral cladribine versus placebo in the treatment of participants who have sustained a first clinical demyelinating event within 75 days prior to the Screening. Participants must have a minimum of 2 clinically silent lesions on the Screening magnetic resonance imaging (MRI). The study will include a pre-study evaluation period (Screening period: between 10 and 28 days prior to the start of treatment with blinded study medication (oral cladribine or placebo). Depending upon the clinical course of their MS, participants will then proceed from the ITP to either the Maintenance Treatment Period (with open-label interferon-beta treatment) or LTFU period (with either open-label low-dose cladribine or no additional treatment (if no progression to MS has been noted after the initial treatment period). The single primary endpoint for the overall study, which will be determined during the ITP, is time to conversion to MS (from randomization), according to the Poser criteria. For every participants, eligibility for study enrollment and entry into each of the study periods, and diagnosis of conversion to either McDonald MS or CDMS must be confirmed and approved by a Sponsor appointed study Adjudication Committee.
Interventions
DRUGCladribine
Cladribine tablets were administered until CDMS conversion, whichever occur first.
DRUGPlacebo
Placebo matched to cladribine tablets were administered.
DRUGRebif® new formulation (RNF)
Participants who converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received RNF subcutaneously at a dose of 44 microgram (mcg) three times a week. Participants who converted to CDMS during long-term follow-up (LTFU) period, received RNF subcutaneously at a dose of 44 mcg three times a week.
Sponsors
EMD Serono Research & Development Institute, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Male or female between 18 and 55 years old, inclusive * Weighed between 40 to 120 kilogram (kg), inclusive * Participant has experienced a single, first clinical event suggestive of MS within 75 days prior to the Screening visit, (clock starts 24 hours after onset). The event must be a new neurological abnormality present for at least 24 hours, either mono- or polysymptomatic * Participant has at least two clinically silent lesions on the T2-weighted MRI scan, at screening, with a size of at least 3 millimeter (mm), at least one of which is ovoid or periventricular or infratentorial on screening MRI * Participant has EDSS 0 - 5.0 at Screening * Participant has no medical history or evidence of latent tuberculosis infection (LTBI) or active tubercular disease, as evidenced by the Mantoux tuberculosis (TB) skin test or a comparable sensitive test according to local regulations/guidelines (if the Mantoux test is not available), and/or a chest X-ray * Participant has normal hematological parameters at Screening, as defined by the central laboratory that performed all the assessments * If female, she must: * be neither pregnant nor breast-feeding, nor attempting to conceive and * use a highly effective method of contraception throughout the entire duration of the study and for 90 days following completion of the last dose of study medication. A highly effective method of contraception is defined as those which result in a low failure rate (that is less than 1 percent per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomized partner, or * be post-menopausal or surgically sterilized (Note: for Danish sites only, participants should use a hormonal contraceptive or intrauterine device for the duration of the trial) * Male participants must be willing to use contraception to avoid impregnating partners throughout the study, and for 90 days following the last dose of study medication * Be willing and able to comply with study procedures for the duration of the study * Participant has to provide written informed consent voluntarily, including, for United states of America (USA), participant authorization under Health Insurance Portability and Accountability Act (HIPAA), prior to any study-related procedure that is not part of normal medical care * Participant has refused any treatment already available for clinically isolated syndrome (CIS) such as interferons or glatiramer acetate, at the time of entry into the Initial Treatment Period of this study
Exclusion criteria
* Participant has a diagnosis of MS (per McDonald criteria, 2005) * Participant has any other disease that could better explain the participant's signs and symptoms * Participant has complete transverse myelitis or bilateral optic neuritis * Participant using or has used any other approved MS disease modifying drug (DMD) * Participant has used any investigational drug or undergone an experimental procedure within 12 weeks prior to Study day 1 * Participant received oral or systemic corticosteroids or adrenocorticotropic hormone (ACTH) within 30 days prior to screening MRI. The MRI had to be performed 30 days after the oral or systemic corticosteroids or ACTH treatment. In case this interfered with MRI timing the screening period could be extended accordingly. * Participant has abnormal total bilirubin, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase greater than 2.5 times the upper limit of normal * Participant suffered from current autoimmune disease other than MS * Participant suffered from psychiatric illness (including history of, or concurrent, severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the participant or could affect compliance with the study protocol * Participant suffered from major medical illness such as cardiac (for example angina, congestive heart failure or arrhythmia), endocrinologic, hepatic, immunologic, metabolic, renal, pulmonary, gastrointestinal, dermatologic, or other major disease that would preclude the administration of oral cladribine * Participant has a history of seizures not adequately controlled by medications * Participant has a known allergy to cladribine, interferon-beta, the excipient(s) of the study medications, or to gadolinium- diethylenetriamine penta-acetic acid (DTPA) * Participant has any renal condition that would preclude the administration of gadolinium (for example acute or chronic severe renal insufficiency (glomerular filtration rate \[GFR\] less than 30 milliliter per minute per 1.73 square meter \[mL/min/1.73 m\^2\]) * Participant has a history of chronic or clinically significant hematological abnormalities * Participant has a history of active or chronic infectious disease or any disease that compromises immune function (for example human immunodeficiency virus positive \[HIV+\], human T-lymphotrophic virus \[HTLV-1\], Lyme disease, latent tuberculosis infection \[LTBI\] or TB, insulin-dependent diabetes). * Participant has previously been screened in this study (signed an informed consent) and then withdrawn * Participant has received any immunomodulatory or immunosuppressive therapy) at any time prior to Study Day 1, including, but not limited to, the following products: any interferon, glatiramer acetate (Copolymer I), cyclophosphamide, cyclosporine, methotrexate, linomide, azathioprine, mitoxantrone, teriflunomide, laquinimod, cladribine, total lymphoid irradiation, anti-lymphocyte monoclonal antibody treatment (for example natalizumab, alemtuzumab/Campath, anti-cluster of differentiation 4 \[CD4\]), intravenous immunoglobulin G (IVIG), cytokines or anti-cytokine therapy * Participant has received experimental MS treatment * Participant has a history of alcohol or drug abuse * Participant has intolerance or any contraindication to both paracetamol (acetaminophen) and ibuprofen * Participant has inability to administer subcutaneous injections either by self or by caregiver * Participant has prior or current malignancy (with the exception of in situ basal or squamous cell skin cancer surgically removed without recurrence for at least five years) * Participant has a positive stool hemoccult test at Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ITP: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS | ITP: Baseline up to Week 96 | CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to Multiple Sclerosis \[MS\]) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (\>=) 1 point if baseline EDSS was between \>= 1.0 and less than or equal to (=\<) 4.5; or \>= 1.5 points if baseline EDSS was 0, or \>= 0.5 if baseline EDSS \>= 5.0 over a period of at least 3 months. Kaplan-Meier estimates were provided for of the cumulative (cum.) percentage (%) of participants with CDMS over time. The probability of patients remaining event-free over time (from randomization) in each of the three treatment groups was displayed in the form of survival curves estimated using the non-parametric Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ITP: Time to Develop Multiple Sclerosis (MS) Conversion According to the Revised McDonald Criteria (2005) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With McDonald MS | ITP: Baseline up to Week 96 | The McDonald criteria use dissemination in time and space established by magnetic resonance imaging (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium enhanced (Gd+) lesion found on a repeat MRI. Dissemination in space is established by the presence of any 3 of the following: 1 Gd+ lesion or 9 T2 bright lesions if there is no enhancement; greater than or equal to 1 infratentorial lesion; greater than or equal to 1 juxtacortical lesion; greater than or equal to 3 periventricular lesions. Kaplan-Meier estimates were provided for the cum. percentage (%) of participants with McDonald MS over time. |
| ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan | ITP: Baseline up to Week 96 | Number of CUA lesions, new or enlarging T2 lesions, and new or persisting T1 Gd+ lesions were measured by using magnetic resonance imaging (MRI) scans. |
| OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | OLMP: Day 1, 90, 180, 270, 360, 450, 540, 630, 720 and 810 | EDSS progression is based on a standardized neurological exam and focuses on symptoms that commonly occur in Multiple Sclerosis (MS). Overall scores ranges from 0.0 (normal) to 10.0 (death due to MS). A sustained progression on EDSS score was defined as an EDSS progression confirmed into two consecutive assessment. Probability of disability progression at different time points was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first EDSS increase. |
| LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Multiple Sclerosis (MS) According to the 2005 McDonald Criteria | Time from Randomization up to 1217 days | The McDonald criteria use dissemination in time and space established by magnetic resonance imaging (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium enhanced (Gd+) lesion found on a repeat MRI. |
| LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria | Time from Randomization up to 1217 days | CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (\>=) 1 point if baseline EDSS was between \>= 1.0 and less than or equal to (=\<) 4.5; or \>= 1.5 points if baseline EDSS was 0, or \>= 0.5 if baseline EDSS \>= 5.0 over a period of at least 3 months. |
| LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria | Time from Randomization up to 1217 days | CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (\>=) 1 point if baseline EDSS was between \>= 1.0 and less than or equal to (=\<) 4.5; or \>= 1.5 points if baseline EDSS was 0, or \>= 0.5 if baseline EDSS \>= 5.0 over a period of at least 3 months. |
| ITP: Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) as Per Poser Criteria | ITP: Baseline up to week 96 | Clinically definite multiple sclerosis (CDMS) according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (\>=) 1 point if baseline EDSS was between \>= 1.0 and less than or equal to (=\<) 4.5; or \>= 1.5 points if baseline EDSS was 0, or \>= 0.5 if baseline EDSS \>= 5.0 over a period of at least 3 months. The percentage of participants who converted to CDMS are reported here. |
| ITP: Number of New or Persisting Gd-enhanced Lesions | ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96 | Number of new or persisting Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. |
| OLMP: Number of New or Persisting Gd-enhanced Lesions | OLMP: Baseline, Week 24, 48, 72 and 96 | Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. |
| LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | LTFU: Baseline, Week 13, 24 and 36 | Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. |
| LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | LTFU: Baseline, Week 13, 24, 36 and 48 | Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. |
| ITP: Number of New or Enlarging T2 Lesions | ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96 | Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans. |
| OLMP: Number of New or Enlarging T2 Lesions | OLMP: Baseline, Week 24, 48, 72 and 96 | Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans. |
| LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions | LTFU: Baseline, Week 13, 24 and 36 | Number of new or enlarging T2 Lesions were measured by using magnetic resonance imaging (MRI) scans. |
| LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions | LTFU: Baseline, Week 13, 24, 36 and 48 | Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans. |
| ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96 | Number of CUA lesions were measured by using magnetic resonance imaging (MRI) scans. |
| OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | OLMP: Baseline, Week 24, 48, 72 and 96 | Number of combined unique active (CUA) lesions were measured by using magnetic resonance imaging (MRI) scans. |
| LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | LTFU: Baseline, Week 13, 24 and 36 | Number of CUA MRI lesions were measured by using magnetic resonance imaging (MRI) scans. |
| LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | LTFU: Baseline, Week 13, 24, 36 and 48 | Number of CUA lesions were measured by using magnetic resonance imaging (MRI) scans. |
| ITP: Change From Baseline in Volume of T1 Gd-Enhanced Lesions | ITP: Baseline, Week 96 | Change in volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans. |
| OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | OLMP: Baseline, Week 24, 48, 72 and 96 | Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans. |
| OLMP: Percent Change From Baseline in Brain Volume | OLMP: Baseline, Week 48 and 96 | Brain volume was measured by using magnetic resonance imaging (MRI) scans. Percent change from baseline in brain volume at Week 48 and 96 was reported. |
| LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | LTFU: Baseline, Week 13, 24 and 36 | Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans. |
| LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | LTFU: Baseline, Week 13, 24, 36 and 48 | Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans. |
| ITP: Changes From Baseline in Volume of T2 Lesions | ITP: Baseline, Week 48 and 96 | Change in volume of T2 lesions from baseline was measured by using magnetic resonance imaging (MRI) scans. |
| OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | OLMP: Baseline, Week 48 and 96 | Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans. |
| LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T2 Lesions | LTFU: Baseline (Day 1) | Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans. |
| LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Baseline, Week 48 | Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans. |
| ITP: Number of T1 Hypointense Lesions | ITP: Baseline, Week 48 and 96 | Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans. |
| OLMP: Number of T1 Hypointense Lesions | OLMP: Baseline, Week 48 and 96 | Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans. |
| LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of T1 Hypointense Lesions | LTFU: Baseline (Day 1) | Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans. |
| LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of T1 Hypointense Lesions | LTFU: Baseline, Week 48 | Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans. |
| ITP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions | ITP: Baseline up to Week 96 | T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported. |
| OLMP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions | OLMP: Baseline up to Week 96 | T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported. |
| LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions | LTFU: Baseline up to Week 48 | T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported. |
| LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions | Baseline up to Week 48 | T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported. |
| ITP: Percentage of Participants With no New or Enlarging T2 Lesions | ITP: Baseline up to Week 96 | T2 lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or enlarging T2 lesions were reported. |
| OLMP: Percentage of Participants With no New or Enlarging T2 Lesions | OLMP: Baseline up to 96 | T2 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or enlarging T2 Lesions were reported. |
| LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions | Baseline up to Week 48 | Enlarging T2 Lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no New or Enlarging T2 Lesions were reported. |
| LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions | LTFU: Baseline up to Week 48 | Enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no New or Enlarging T2 lesions were reported. |
| ITP: Percent Change From Baseline in Brain Volume | ITP: Baseline, Week 48 and 96 | Brain volume was measured by using magnetic resonance imaging (MRI) scans. Percent change from baseline in brain volume at Week 48 and 96 was reported. |
| ITP: Percentage of Participants Converting to McDonald Multiple Sclerosis (MS) (2005) | ITP: Baseline up to week 96 | Percentage of participants converting to mcDonald multiple sclerosis (2005) were reported. |
| LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Relapses | Baseline up to Week 48 | Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. |
| LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Relapses | Baseline up to Week 48 | Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. |
| OLMP: Annualized Relapse Rate | Baseline up to Week 96 | The annualized relapse rate for each treatment group was the mean of the annualized relapse rates for all the participants in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25. Where, Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. |
| OLMP: Percentage of Relapse-Free Participants | Baseline up to Week 96 | Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of relapse-free participants were reported. |
| ITP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | ITP: Baseline up to Week 96 | An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. Number of Participants with TEAEs and serious TEAEs were reported. |
| OLMP: Number of Relapses | Baseline up to Week 96 | Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. |
Countries
Argentina, Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Croatia, Czechia, Estonia, Finland, France, Georgia, Germany, India, Italy, Lebanon, North Macedonia, Norway, Poland, Portugal, Romania, Russia, Serbia, Singapore, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Arab Emirates, United Kingdom, United States
Participant flow
Recruitment details
A total of 617 participants were randomized for initial treatment period (ITP) and 616 participants received study drug.
Participants by arm
| Arm | Count |
|---|---|
| Cladribine 5.25 mg/kg Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first. Participants who converted to CDMS during ITP entered OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Participants who did not convert to CDMS during ITP, entered in LTFU period. Participants who converted to McDonald MS during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. | 204 |
| Cladribine 3.5 mg/kg Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first. Participants who converted to CDMS during ITP entered OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Participants who did not convert to CDMS during ITP, entered in LTFU period. Participants who converted to McDonald MS during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any study treatment during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. | 206 |
| Placebo Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first. Participants who converted to CDMS during ITP entered OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Participants who did not convert to CDMS during ITP, entered in LTFU period. Participants who converted to McDonald MS during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any study treatment during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. | 206 |
| Total | 616 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ITP- Treatment Disposition | Adverse Event | 20 | 10 | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| ITP- Treatment Disposition | Converted to CDMS | 30 | 27 | 71 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| ITP- Treatment Disposition | Lost to Follow-up | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| ITP- Treatment Disposition | Other | 50 | 38 | 24 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| ITP- Treatment Disposition | Randomized but not treated | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| LTFU (Cladribine Treatment) (48 Weeks) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| LTFU (Cladribine Treatment) (48 Weeks) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| LTFU (Cladribine Treatment) (48 Weeks) | Other | 0 | 0 | 0 | 0 | 0 | 0 | 9 | 8 | 16 | 0 | 0 | 0 |
| LTFU (No Cladribine) (48 Weeks) | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 34 | 36 | 14 |
| OLMP (Up to 96 Weeks) | Adverse Event | 0 | 0 | 0 | 2 | 2 | 5 | 0 | 0 | 0 | 0 | 0 | 0 |
| OLMP (Up to 96 Weeks) | Death | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| OLMP (Up to 96 Weeks) | Disease progression | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 0 |
| OLMP (Up to 96 Weeks) | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| OLMP (Up to 96 Weeks) | Other | 0 | 0 | 0 | 15 | 20 | 44 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cladribine 5.25 mg/kg | Cladribine 3.5 mg/kg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 31.9 years STANDARD_DEVIATION 8.8 | 31.7 years STANDARD_DEVIATION 9.2 | 32.2 years STANDARD_DEVIATION 8.2 | 31.9 years STANDARD_DEVIATION 8.7 |
| Age, Customized Greater than or equal to 30 years | 111 Participants | 110 Participants | 113 Participants | 334 Participants |
| Age, Customized Less than 30 years | 93 Participants | 96 Participants | 93 Participants | 282 Participants |
| Expanded disability status scale (EDSS) score | 1.6 units on scale STANDARD_DEVIATION 0.9 | 1.6 units on scale STANDARD_DEVIATION 0.9 | 1.7 units on scale STANDARD_DEVIATION 0.9 | 1.6 units on scale STANDARD_DEVIATION 0.9 |
| Monofocal/Multifocal Classification (By Adjudication Committee) Monofocal | 108 Participants | 112 Participants | 101 Participants | 321 Participants |
| Monofocal/Multifocal Classification (By Adjudication Committee) Multifocal | 96 Participants | 94 Participants | 105 Participants | 295 Participants |
| Number of participants Using Steroid Treatment | 133 Participants | 131 Participants | 140 Participants | 404 Participants |
| Number of Participants with Time Constant 1 (T1) Gd-enhanced Lesions | 90 Participants | 74 Participants | 73 Participants | 237 Participants |
| Number of T2 Lesions | 29.7 lesions STANDARD_DEVIATION 29.6 | 26.8 lesions STANDARD_DEVIATION 28.3 | 26.3 lesions STANDARD_DEVIATION 27.4 | 27.6 lesions STANDARD_DEVIATION 28.4 |
| Number of Time Constant 1 (T1) Gadolinium Enhanced (GD+) lesions | 1.9 lesions STANDARD_DEVIATION 5.8 | 1.5 lesions STANDARD_DEVIATION 4.5 | 0.9 lesions STANDARD_DEVIATION 2.5 | 1.4 lesions STANDARD_DEVIATION 4.5 |
| Sex: Female, Male Female | 132 Participants | 130 Participants | 138 Participants | 400 Participants |
| Sex: Female, Male Male | 72 Participants | 76 Participants | 68 Participants | 216 Participants |
| Time from First Demyelinating Event to Randomization | 79.35 Days STANDARD_DEVIATION 17.61 | 78.67 Days STANDARD_DEVIATION 15.97 | 79.40 Days STANDARD_DEVIATION 17.94 | 79.14 Days STANDARD_DEVIATION 17.17 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 204 | 0 / 206 | 0 / 206 | 0 / 24 | 1 / 25 | 0 / 60 | 0 / 9 | 0 / 9 | 0 / 16 | 0 / 34 | 0 / 36 | 0 / 14 |
| other Total, other adverse events | 133 / 204 | 132 / 206 | 116 / 206 | 18 / 24 | 19 / 25 | 41 / 60 | 3 / 9 | 4 / 9 | 7 / 16 | 2 / 34 | 0 / 36 | 2 / 14 |
| serious Total, serious adverse events | 12 / 204 | 23 / 206 | 22 / 206 | 1 / 24 | 4 / 25 | 5 / 60 | 0 / 9 | 0 / 9 | 1 / 16 | 0 / 34 | 1 / 36 | 0 / 14 |
Outcome results
Primary
ITP: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS
CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to Multiple Sclerosis \[MS\]) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (\>=) 1 point if baseline EDSS was between \>= 1.0 and less than or equal to (=\<) 4.5; or \>= 1.5 points if baseline EDSS was 0, or \>= 0.5 if baseline EDSS \>= 5.0 over a period of at least 3 months. Kaplan-Meier estimates were provided for of the cumulative (cum.) percentage (%) of participants with CDMS over time. The probability of patients remaining event-free over time (from randomization) in each of the three treatment groups was displayed in the form of survival curves estimated using the non-parametric Kaplan-Meier method.
Time frame: ITP: Baseline up to Week 96
Population: The intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | ITP: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS | 15.8 Cum. % of participants with CDMS |
| Cladribine 3.5 mg/kg (ITP) | ITP: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS | 14.0 Cum. % of participants with CDMS |
| Placebo (ITP) | ITP: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS | 37.8 Cum. % of participants with CDMS |
p-value: <0.000195% CI: [0.248, 0.584]two-sided Wald test
p-value: <0.000195% CI: [0.21, 0.509]two-sided Wald test
Secondary
ITP: Change From Baseline in Volume of T1 Gd-Enhanced Lesions
Change in volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
Time frame: ITP: Baseline, Week 96
Population: ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here Number of participants analyzed signifies those participants who were evaluable for this outcome measure and Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | ITP: Change From Baseline in Volume of T1 Gd-Enhanced Lesions | -73.97 cubic millimeters (mm^3) | Standard Deviation 204.8 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Change From Baseline in Volume of T1 Gd-Enhanced Lesions | -126.64 cubic millimeters (mm^3) | Standard Deviation 399.39 |
| Placebo (ITP) | ITP: Change From Baseline in Volume of T1 Gd-Enhanced Lesions | 48.63 cubic millimeters (mm^3) | Standard Deviation 239.03 |
p-value: <0.000195% CI: [-37.2, 0]ANCOVA
p-value: <0.000195% CI: [-117.3, 0]ANCOVA
Secondary
ITP: Changes From Baseline in Volume of T2 Lesions
Change in volume of T2 lesions from baseline was measured by using magnetic resonance imaging (MRI) scans.
Time frame: ITP: Baseline, Week 48 and 96
Population: ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here Number analyzed = participants evaluable at specified timepoint for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | ITP: Changes From Baseline in Volume of T2 Lesions | Change at Week 48 | -654.20 mm^3 | Standard Deviation 2061.85 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Changes From Baseline in Volume of T2 Lesions | Baseline | 3825.73 mm^3 | Standard Deviation 5093.52 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Changes From Baseline in Volume of T2 Lesions | Change at Week 96 | -1237.44 mm^3 | Standard Deviation 2718.76 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Changes From Baseline in Volume of T2 Lesions | Change at Week 48 | -828.97 mm^3 | Standard Deviation 3513.04 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Changes From Baseline in Volume of T2 Lesions | Baseline | 3435.22 mm^3 | Standard Deviation 5184.12 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Changes From Baseline in Volume of T2 Lesions | Change at Week 96 | -1605.63 mm^3 | Standard Deviation 2889.61 |
| Placebo (ITP) | ITP: Changes From Baseline in Volume of T2 Lesions | Baseline | 3436.69 mm^3 | Standard Deviation 4613.43 |
| Placebo (ITP) | ITP: Changes From Baseline in Volume of T2 Lesions | Change at Week 96 | -886.39 mm^3 | Standard Deviation 2955.44 |
| Placebo (ITP) | ITP: Changes From Baseline in Volume of T2 Lesions | Change at Week 48 | -29.57 mm^3 | Standard Deviation 2581.44 |
Secondary
ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan
Number of CUA lesions, new or enlarging T2 lesions, and new or persisting T1 Gd+ lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: ITP: Baseline up to Week 96
Population: The ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan | New or persisting T1 Gd+ lesions | 0.61 Lesions | Standard Deviation 5.33 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan | CUA lesions | 1.20 Lesions | Standard Deviation 5.79 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan | New or enlarging T2 lesions | 0.62 Lesions | Standard Deviation 1.9 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan | New or persisting T1 Gd+ lesions | 0.29 Lesions | Standard Deviation 0.97 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan | CUA lesions | 0.65 Lesions | Standard Deviation 1.8 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan | New or enlarging T2 lesions | 0.40 Lesions | Standard Deviation 1.12 |
| Placebo (ITP) | ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan | CUA lesions | 2.13 Lesions | Standard Deviation 2.87 |
| Placebo (ITP) | ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan | New or enlarging T2 lesions | 1.17 Lesions | Standard Deviation 1.87 |
| Placebo (ITP) | ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan | New or persisting T1 Gd+ lesions | 0.97 Lesions | Standard Deviation 1.62 |
Comparison: CUA lesionsp-value: <0.000195% CI: [-0.971, -0.5]ANCOVA
Comparison: CUA lesionsp-value: <0.000195% CI: [-0.857, -0.429]ANCOVA
Comparison: T1 Gd-Enhancing Lesionsp-value: <0.000195% CI: [-0.333, -0.167]ANCOVA
Comparison: T1 Gd-Enhancing Lesionsp-value: <0.000195% CI: [-0.375, -0.167]ANCOVA
Comparison: T2 Lesionsp-value: <0.000195% CI: [-0.5, -0.167]ANCOVA
Comparison: T2 Lesionsp-value: <0.000195% CI: [-0.429, -0.143]ANCOVA
Secondary
ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Number of CUA lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
Population: ITT population included all randomized participants who received at least 1 dose of ITP study medication. Here Number of participants analyzed signifies those who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 36 | 0.16 Lesions | Standard Deviation 0.71 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 96 | 0.11 Lesions | Standard Deviation 0.6 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 60 | 0.23 Lesions | Standard Deviation 1.4 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 48 | 0.09 Lesions | Standard Deviation 0.59 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 84 | 0.11 Lesions | Standard Deviation 0.51 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 24 | 0.26 Lesions | Standard Deviation 1.03 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 13 | 2.37 Lesions | Standard Deviation 6.87 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 72 | 0.08 Lesions | Standard Deviation 0.72 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 72 | 0.22 Lesions | Standard Deviation 1.03 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 13 | 1.56 Lesions | Standard Deviation 4.04 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 24 | 0.29 Lesions | Standard Deviation 0.89 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 36 | 0.25 Lesions | Standard Deviation 0.7 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 48 | 0.56 Lesions | Standard Deviation 3.05 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 60 | 0.42 Lesions | Standard Deviation 1.87 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 84 | 0.55 Lesions | Standard Deviation 4.52 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 96 | 0.23 Lesions | Standard Deviation 1.39 |
| Placebo (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 60 | 1.44 Lesions | Standard Deviation 2.7 |
| Placebo (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 24 | 1.91 Lesions | Standard Deviation 2.93 |
| Placebo (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 13 | 2.41 Lesions | Standard Deviation 3.89 |
| Placebo (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 96 | 0.99 Lesions | Standard Deviation 1.89 |
| Placebo (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 84 | 1.14 Lesions | Standard Deviation 1.95 |
| Placebo (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 48 | 1.89 Lesions | Standard Deviation 2.78 |
| Placebo (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 36 | 1.84 Lesions | Standard Deviation 2.64 |
| Placebo (ITP) | ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 72 | 1.66 Lesions | Standard Deviation 3.05 |
Secondary
ITP: Number of New or Enlarging T2 Lesions
Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
Population: The intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here Number analyzed signifies those participants who were evaluable at specified time point for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 24 | 0.24 Lesions | Standard Deviation 0.95 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 13 | 1.56 Lesions | Standard Deviation 3.52 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 36 | 0.09 Lesions | Standard Deviation 0.4 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 48 | 0.07 Lesions | Standard Deviation 0.5 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 60 | 0.13 Lesions | Standard Deviation 0.63 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 72 | 0.03 Lesions | Standard Deviation 0.22 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 84 | 0.09 Lesions | Standard Deviation 0.46 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 96 | 0.04 Lesions | Standard Deviation 0.25 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 36 | 0.12 Lesions | Standard Deviation 0.42 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 84 | 0.28 Lesions | Standard Deviation 2.03 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 48 | 0.32 Lesions | Standard Deviation 2.52 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 60 | 0.25 Lesions | Standard Deviation 1.09 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 72 | 0.10 Lesions | Standard Deviation 0.34 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 13 | 1.25 Lesions | Standard Deviation 3.33 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 24 | 0.20 Lesions | Standard Deviation 0.66 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 96 | 0.10 Lesions | Standard Deviation 0.59 |
| Placebo (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 36 | 1.14 Lesions | Standard Deviation 1.87 |
| Placebo (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 72 | 0.83 Lesions | Standard Deviation 1.77 |
| Placebo (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 24 | 1.01 Lesions | Standard Deviation 1.7 |
| Placebo (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 48 | 1.04 Lesions | Standard Deviation 1.54 |
| Placebo (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 84 | 0.61 Lesions | Standard Deviation 1.31 |
| Placebo (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 13 | 1.43 Lesions | Standard Deviation 2.56 |
| Placebo (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 60 | 0.71 Lesions | Standard Deviation 1.57 |
| Placebo (ITP) | ITP: Number of New or Enlarging T2 Lesions | Week 96 | 0.38 Lesions | Standard Deviation 0.85 |
Secondary
ITP: Number of New or Persisting Gd-enhanced Lesions
Number of new or persisting Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
Population: The intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here Number analyzed signifies those participants who were evaluable at specified time point for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 13 | 0.86 Lesions | Standard Deviation 5.6 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 24 | 0.03 Lesions | Standard Deviation 0.2 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 36 | 0.08 Lesions | Standard Deviation 0.38 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 48 | 0.02 Lesions | Standard Deviation 0.13 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 60 | 0.10 Lesions | Standard Deviation 0.84 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 72 | 0.05 Lesions | Standard Deviation 0.53 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 84 | 0.02 Lesions | Standard Deviation 0.13 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 96 | 0.07 Lesions | Standard Deviation 0.43 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 36 | 0.14 Lesions | Standard Deviation 0.44 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 84 | 0.32 Lesions | Standard Deviation 2.62 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 48 | 0.27 Lesions | Standard Deviation 0.92 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 60 | 0.22 Lesions | Standard Deviation 0.94 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 72 | 0.16 Lesions | Standard Deviation 0.81 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 13 | 0.37 Lesions | Standard Deviation 1.52 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 24 | 0.13 Lesions | Standard Deviation 0.51 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 96 | 0.18 Lesions | Standard Deviation 0.84 |
| Placebo (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 36 | 0.74 Lesions | Standard Deviation 1.28 |
| Placebo (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 24 | 0.92 Lesions | Standard Deviation 1.69 |
| Placebo (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 13 | 1.00 Lesions | Standard Deviation 1.98 |
| Placebo (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 48 | 0.87 Lesions | Standard Deviation 1.81 |
| Placebo (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 84 | 0.60 Lesions | Standard Deviation 1.2 |
| Placebo (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 72 | 0.90 Lesions | Standard Deviation 1.88 |
| Placebo (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 60 | 0.74 Lesions | Standard Deviation 1.61 |
| Placebo (ITP) | ITP: Number of New or Persisting Gd-enhanced Lesions | Week 96 | 0.64 Lesions | Standard Deviation 1.25 |
Secondary
ITP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. Number of Participants with TEAEs and serious TEAEs were reported.
Time frame: ITP: Baseline up to Week 96
Population: Safety analysis set included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo) and had at least one safety assessment during the ITP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 165 Participants |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 12 Participants |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 168 Participants |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 23 Participants |
| Placebo (ITP) | ITP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 162 Participants |
| Placebo (ITP) | ITP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 22 Participants |
Secondary
ITP: Number of T1 Hypointense Lesions
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: ITP: Baseline, Week 48 and 96
Population: ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here Number analyzed = participants evaluable at specified timepoint for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of T1 Hypointense Lesions | Week 48 | 8.39 Lesions | Standard Deviation 12.6 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of T1 Hypointense Lesions | Baseline | 8.0 Lesions | Standard Deviation 11.7 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Number of T1 Hypointense Lesions | Week 96 | 5.35 Lesions | Standard Deviation 8.14 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of T1 Hypointense Lesions | Week 48 | 6.95 Lesions | Standard Deviation 12.86 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of T1 Hypointense Lesions | Baseline | 7.3 Lesions | Standard Deviation 12.2 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Number of T1 Hypointense Lesions | Week 96 | 3.82 Lesions | Standard Deviation 6.89 |
| Placebo (ITP) | ITP: Number of T1 Hypointense Lesions | Baseline | 7.0 Lesions | Standard Deviation 8.6 |
| Placebo (ITP) | ITP: Number of T1 Hypointense Lesions | Week 96 | 5.06 Lesions | Standard Deviation 6.82 |
| Placebo (ITP) | ITP: Number of T1 Hypointense Lesions | Week 48 | 7.07 Lesions | Standard Deviation 8.75 |
Secondary
ITP: Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) as Per Poser Criteria
Clinically definite multiple sclerosis (CDMS) according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (\>=) 1 point if baseline EDSS was between \>= 1.0 and less than or equal to (=\<) 4.5; or \>= 1.5 points if baseline EDSS was 0, or \>= 0.5 if baseline EDSS \>= 5.0 over a period of at least 3 months. The percentage of participants who converted to CDMS are reported here.
Time frame: ITP: Baseline up to week 96
Population: ITT analysis set included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | ITP: Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) as Per Poser Criteria | 28.8 Percentage of participants |
| Cladribine 3.5 mg/kg (ITP) | ITP: Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) as Per Poser Criteria | 23.1 Percentage of participants |
| Placebo (ITP) | ITP: Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) as Per Poser Criteria | 56.3 Percentage of participants |
Secondary
ITP: Percentage of Participants Converting to McDonald Multiple Sclerosis (MS) (2005)
Percentage of participants converting to mcDonald multiple sclerosis (2005) were reported.
Time frame: ITP: Baseline up to week 96
Population: Intent-to-Treat analysis set included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | ITP: Percentage of Participants Converting to McDonald Multiple Sclerosis (MS) (2005) | 70.7 Percentage of participants |
| Cladribine 3.5 mg/kg (ITP) | ITP: Percentage of Participants Converting to McDonald Multiple Sclerosis (MS) (2005) | 71.6 Percentage of participants |
| Placebo (ITP) | ITP: Percentage of Participants Converting to McDonald Multiple Sclerosis (MS) (2005) | 91.8 Percentage of participants |
Secondary
ITP: Percentage of Participants With no New or Enlarging T2 Lesions
T2 lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or enlarging T2 lesions were reported.
Time frame: ITP: Baseline up to Week 96
Population: The ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | ITP: Percentage of Participants With no New or Enlarging T2 Lesions | 32.9 Percentage of Participants |
| Cladribine 3.5 mg/kg (ITP) | ITP: Percentage of Participants With no New or Enlarging T2 Lesions | 35.1 Percentage of Participants |
| Placebo (ITP) | ITP: Percentage of Participants With no New or Enlarging T2 Lesions | 19.0 Percentage of Participants |
Secondary
ITP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
Time frame: ITP: Baseline up to Week 96
Population: The ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | ITP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions | 67.0 Percentage of Participants |
| Cladribine 3.5 mg/kg (ITP) | ITP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions | 57.1 Percentage of Participants |
| Placebo (ITP) | ITP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions | 21.6 Percentage of Participants |
Secondary
ITP: Percent Change From Baseline in Brain Volume
Brain volume was measured by using magnetic resonance imaging (MRI) scans. Percent change from baseline in brain volume at Week 48 and 96 was reported.
Time frame: ITP: Baseline, Week 48 and 96
Population: The ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here Number of participants analyzed signifies those participants who were evaluable for this outcome measure and Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | ITP: Percent Change From Baseline in Brain Volume | Week 48 | -0.47 Percent change | Standard Deviation 0.63 |
| Cladribine 5.25 mg/kg (ITP) | ITP: Percent Change From Baseline in Brain Volume | Week 96 | -0.59 Percent change | Standard Deviation 0.8 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Percent Change From Baseline in Brain Volume | Week 48 | -0.48 Percent change | Standard Deviation 0.69 |
| Cladribine 3.5 mg/kg (ITP) | ITP: Percent Change From Baseline in Brain Volume | Week 96 | -0.72 Percent change | Standard Deviation 0.73 |
| Placebo (ITP) | ITP: Percent Change From Baseline in Brain Volume | Week 96 | -0.75 Percent change | Standard Deviation 0.65 |
| Placebo (ITP) | ITP: Percent Change From Baseline in Brain Volume | Week 48 | -0.33 Percent change | Standard Deviation 0.76 |
Secondary
ITP: Time to Develop Multiple Sclerosis (MS) Conversion According to the Revised McDonald Criteria (2005) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With McDonald MS
The McDonald criteria use dissemination in time and space established by magnetic resonance imaging (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium enhanced (Gd+) lesion found on a repeat MRI. Dissemination in space is established by the presence of any 3 of the following: 1 Gd+ lesion or 9 T2 bright lesions if there is no enhancement; greater than or equal to 1 infratentorial lesion; greater than or equal to 1 juxtacortical lesion; greater than or equal to 3 periventricular lesions. Kaplan-Meier estimates were provided for the cum. percentage (%) of participants with McDonald MS over time.
Time frame: ITP: Baseline up to Week 96
Population: The ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | ITP: Time to Develop Multiple Sclerosis (MS) Conversion According to the Revised McDonald Criteria (2005) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With McDonald MS | 51.36 Cum. % of participants with McDonald MS |
| Cladribine 3.5 mg/kg (ITP) | ITP: Time to Develop Multiple Sclerosis (MS) Conversion According to the Revised McDonald Criteria (2005) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With McDonald MS | 56.05 Cum. % of participants with McDonald MS |
| Placebo (ITP) | ITP: Time to Develop Multiple Sclerosis (MS) Conversion According to the Revised McDonald Criteria (2005) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With McDonald MS | 87.14 Cum. % of participants with McDonald MS |
p-value: <0.000195% CI: [0.331, 0.547]two-sided Wald test
p-value: <0.000195% CI: [0.39, 0.633]two-sided Wald test
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
Time frame: LTFU: Baseline, Week 13, 24, 36 and 48
Population: LTFU analysis set (No Treatment at LTFU Entry) was used. Here Number analyzed = participants evaluable at specified timepoint for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 36 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 48 | 0.00 mm^3 | — |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 13 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 48 | 0.00 mm^3 | — |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 36 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 13 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Baseline | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 24 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 24 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 24 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Baseline | 4.45 mm^3 | Standard Deviation 21.25 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 13 | 7.34 mm^3 | Standard Deviation 27.76 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 36 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 13 | 0.38 mm^3 | Standard Deviation 1.32 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 24 | -2.48 mm^3 | Standard Deviation 9.6 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 36 | -5.31 mm^3 | Standard Deviation 14.06 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 13 | 17.43 mm^3 | Standard Deviation 57.8 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 36 | -31.48 mm^3 | Standard Deviation 54.53 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 24 | -20.60 mm^3 | Standard Deviation 57.89 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Baseline | 27.79 mm^3 | Standard Deviation 76.02 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 36 | 57.22 mm^3 | Standard Deviation 99.1 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 24 | 57.22 mm^3 | Standard Deviation 127.95 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 13 | -17.95 mm^3 | Standard Deviation 41.38 |
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions
Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
Time frame: Baseline, Week 48
Population: LTFU analysis set (No Treatment at LTFU Entry) was used. Here Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Baseline | 1402.08 mm^3 | Standard Deviation 1799.96 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Week 48 | 0.00 mm^3 | — |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Change at Week 48 | -969.90 mm^3 | — |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Baseline | 962.26 mm^3 | Standard Deviation 1026.99 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Baseline | 1407.75 mm^3 | Standard Deviation 1890.94 |
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Number of CUA lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: LTFU: Baseline, Week 13, 24, 36 and 48
Population: LTFU analysis set (No Treatment at LTFU Entry) was used. Here Number analyzed signifies those participants who were evaluable at specified time point for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 48 | 0.00 Lesions | — |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 13 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 24 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 36 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Baseline | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 13 | 0.04 Lesions | Standard Deviation 0.21 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 36 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 24 | 0.13 Lesions | Standard Deviation 0.35 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Baseline | 0.03 Lesions | Standard Deviation 0.17 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 13 | 0.18 Lesions | Standard Deviation 0.4 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Baseline | 0.14 Lesions | Standard Deviation 0.36 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 36 | 0.33 Lesions | Standard Deviation 0.58 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 24 | 0.00 Lesions | Standard Deviation 0 |
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions
Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: LTFU: Baseline, Week 13, 24, 36 and 48
Population: LTFU analysis set (No Treatment at LTFU Entry) was used. Here Number analyzed signifies those participants who were evaluable at specified time point for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 48 | 0.00 Lesions | — |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 13 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 24 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 36 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions | Baseline | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 13 | 0.04 Lesions | Standard Deviation 0.21 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 36 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 24 | 0.13 Lesions | Standard Deviation 0.35 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions | Baseline | 0.03 Lesions | Standard Deviation 0.17 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 13 | 0.18 Lesions | Standard Deviation 0.4 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions | Baseline | 0.07 Lesions | Standard Deviation 0.27 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 36 | 0.33 Lesions | Standard Deviation 0.58 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 24 | 0.00 Lesions | Standard Deviation 0 |
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions
Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: LTFU: Baseline, Week 13, 24, 36 and 48
Population: LTFU analysis set (No Treatment at LTFU Entry) was used. Here Number analyzed signifies those participants who were evaluable at specified time point for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 48 | 0.00 Lesions | — |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 13 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 24 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 36 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Baseline | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 13 | 0.07 Lesions | Standard Deviation 0.23 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 36 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 24 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Baseline | 0.06 Lesions | Standard Deviation 0.23 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 13 | 0.09 Lesions | Standard Deviation 0.3 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Baseline | 0.14 Lesions | Standard Deviation 0.36 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 36 | 0.17 Lesions | Standard Deviation 0.29 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 24 | 0.20 Lesions | Standard Deviation 0.45 |
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Relapses
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Time frame: Baseline up to Week 48
Population: LTFU analysis set (No Treatment at LTFU Entry) was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Relapses | 0.03 Relapses | Standard Deviation 0.17 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Relapses | 0.03 Relapses | Standard Deviation 0.17 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Relapses | 0.00 Relapses | Standard Deviation 0 |
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of T1 Hypointense Lesions
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: LTFU: Baseline, Week 48
Population: LTFU analysis set (No Treatment at LTFU Entry) was used. Here Number analyzed signifies those participants who were evaluable at specified time point for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of T1 Hypointense Lesions | Baseline | 5.74 Lesions | Standard Deviation 8.21 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of T1 Hypointense Lesions | Week 48 | 4.50 Lesions | — |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of T1 Hypointense Lesions | Baseline | 3.53 Lesions | Standard Deviation 5.78 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of T1 Hypointense Lesions | Baseline | 2.93 Lesions | Standard Deviation 4.46 |
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions
Enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no New or Enlarging T2 lesions were reported.
Time frame: LTFU: Baseline up to Week 48
Population: LTFU analysis set (No Treatment at LTFU Entry) was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions | 0 Percentage of participants |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions | 0 Percentage of participants |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions | 0 Percentage of participants |
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
Time frame: Baseline up to Week 48
Population: LTFU analysis set (No Treatment at LTFU Entry) was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions | 0 Percentage of participants |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions | 0 Percentage of participants |
| Placebo (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions | 0 Percentage of participants |
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria
CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (\>=) 1 point if baseline EDSS was between \>= 1.0 and less than or equal to (=\<) 4.5; or \>= 1.5 points if baseline EDSS was 0, or \>= 0.5 if baseline EDSS \>= 5.0 over a period of at least 3 months.
Time frame: Time from Randomization up to 1217 days
Population: LTFU analysis set (No Treatment at LTFU Entry) was used. Here Number of Participants Analyzed signifies those participants who have been converted to CDMS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria | 773 Days |
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Multiple Sclerosis (MS) According to the 2005 McDonald Criteria
The McDonald criteria use dissemination in time and space established by magnetic resonance imaging (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium enhanced (Gd+) lesion found on a repeat MRI.
Time frame: Time from Randomization up to 1217 days
Population: LTFU analysis set (No Treatment at LTFU Entry) consists of all participants who completed the 96-week ITP and entered the LTFU for safety follow-up and did not receive study treatment upon entry to the LTFU. Here Number of Participants analyzed signifies those participants who have been converted to CDMS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Multiple Sclerosis (MS) According to the 2005 McDonald Criteria | 773 Days |
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
Time frame: LTFU: Baseline, Week 13, 24 and 36
Population: LTFU analysis set (Treated at LTFU Entry) was used. Here Number analyzed = participants evaluable at specified timepoint for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 24 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 13 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 36 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Baseline | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 24 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 36 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 13 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Baseline | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 13 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 24 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 36 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 24 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 36 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 13 | 0.00 mm^3 | Standard Deviation 0 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 36 | -58.93 mm^3 | Standard Deviation 85.19 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Baseline | 79.43 mm^3 | Standard Deviation 143.64 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 13 | 20.56 mm^3 | Standard Deviation 70.96 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 24 | 25.23 mm^3 | Standard Deviation 66.24 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 36 | 0.00 mm^3 | Standard Deviation 0 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 24 | -32.25 mm^3 | Standard Deviation 113.96 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 13 | -63.83 mm^3 | Standard Deviation 147.43 |
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T2 Lesions
Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
Time frame: LTFU: Baseline (Day 1)
Population: LTFU analysis set (Treated at LTFU Entry) was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T2 Lesions | 1217.53 mm^3 | Standard Deviation 1991.21 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T2 Lesions | 587.79 mm^3 | Standard Deviation 1491.2 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T2 Lesions | 702.30 mm^3 | Standard Deviation 1254.66 |
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Number of CUA MRI lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: LTFU: Baseline, Week 13, 24 and 36
Population: LTFU analysis set (Treated at LTFU Entry) analysis set consisted of all participants who converted to McDonald MS (2005) during the ITP, completed ITP 96-weeks and entered the LTFU. Here Number analyzed signifies those participants who were evaluable at specified time point for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 24 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 13 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 36 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Baseline | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 13 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 36 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Baseline | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 24 | 0.25 Lesions | Standard Deviation 0.46 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Baseline | 1.24 Lesions | Standard Deviation 2.49 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 36 | 0.10 Lesions | Standard Deviation 0.32 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 24 | 0.18 Lesions | Standard Deviation 0.4 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 13 | 2.19 Lesions | Standard Deviation 4.46 |
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions
Number of new or enlarging T2 Lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: LTFU: Baseline, Week 13, 24 and 36
Population: LTFU analysis set (Treated at LTFU Entry) analysis set consisted of all participants who converted to McDonald MS (2005) during the ITP, completed ITP 96-weeks and entered the LTFU. Here Number analyzed signifies those participants who were evaluable at specified time point for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions | Baseline | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 13 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 24 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 36 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 36 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions | Baseline | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 24 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 13 | 0.25 Lesions | Standard Deviation 0.46 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 36 | 0.10 Lesions | Standard Deviation 0.32 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 13 | 2.06 Lesions | Standard Deviation 4.25 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions | Week 24 | 0.00 Lesions | Standard Deviation 0 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions | Baseline | 0.71 Lesions | Standard Deviation 1.53 |
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions
Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: LTFU: Baseline, Week 13, 24 and 36
Population: LTFU analysis set (Treated at LTFU Entry) analysis set consisted of all participants who converted to McDonald MS (2005) during the ITP, completed ITP 96-weeks and entered the LTFU. Here Number analyzed signifies those participants who were evaluable at specified time point for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Baseline | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 13 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 24 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 36 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 36 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Baseline | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 24 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 13 | 0.00 Lesions | Standard Deviation 0 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 36 | 0.00 Lesions | Standard Deviation 0 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 13 | 0.13 Lesions | Standard Deviation 0.34 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Week 24 | 0.18 Lesions | Standard Deviation 0.4 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions | Baseline | 0.71 Lesions | Standard Deviation 1.16 |
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Relapses
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Time frame: Baseline up to Week 48
Population: LTFU analysis set (Treated at LTFU Entry) was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Relapses | 0.00 Relapses | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Relapses | 0.00 Relapses | Standard Deviation 0 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Relapses | 0.06 Relapses | Standard Deviation 0.24 |
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of T1 Hypointense Lesions
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: LTFU: Baseline (Day 1)
Population: LTFU analysis set (Treated at LTFU Entry) analysis set consisted of all participants who converted to McDonald MS (2005) during the ITP, completed ITP 96-weeks and entered the LTFU.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of T1 Hypointense Lesions | 4.44 Lesions | Standard Deviation 7.25 |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of T1 Hypointense Lesions | 1.22 Lesions | Standard Deviation 3.31 |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of T1 Hypointense Lesions | 2.24 Lesions | Standard Deviation 5.01 |
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions
Enlarging T2 Lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no New or Enlarging T2 Lesions were reported.
Time frame: Baseline up to Week 48
Population: LTFU analysis set (Treated at LTFU Entry) was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions | 0 Percentage of Participants |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions | 0 Percentage of Participants |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions | 0 Percentage of Participants |
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
Time frame: LTFU: Baseline up to Week 48
Population: LTFU analysis set (Treated at LTFU Entry) was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions | 0 Percentage of Participants |
| Cladribine 3.5 mg/kg (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions | 0 Percentage of Participants |
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions | 0 Percentage of Participants |
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria
CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (\>=) 1 point if baseline EDSS was between \>= 1.0 and less than or equal to (=\<) 4.5; or \>= 1.5 points if baseline EDSS was 0, or \>= 0.5 if baseline EDSS \>= 5.0 over a period of at least 3 months.
Time frame: Time from Randomization up to 1217 days
Population: LTFU analysis set (Treated at LTFU Entry) analysis set consisted of all participants who converted to McDonald MS (2005) during the ITP, completed ITP 96-weeks and entered the LTFU. Here Number of Participants analyzed signifies those participants who have been converted to CDMS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (ITP) | LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria | 767 Days |
Secondary
OLMP: Annualized Relapse Rate
The annualized relapse rate for each treatment group was the mean of the annualized relapse rates for all the participants in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25. Where, Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Time frame: Baseline up to Week 96
Population: OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | OLMP: Annualized Relapse Rate | 0.24 relapses per year |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Annualized Relapse Rate | 0.14 relapses per year |
| Placebo (ITP) | OLMP: Annualized Relapse Rate | 0.42 relapses per year |
Secondary
OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
Time frame: OLMP: Baseline, Week 24, 48, 72 and 96
Population: OLMP Analysis Set was used. Here Number of participants analyzed signifies those participants who were evaluable for this outcome measure and Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 24 | -87.30 mm^3 | Standard Deviation 379.5 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 48 | -106.82 mm^3 | Standard Deviation 415.7 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 24 | 7.71 mm^3 | Standard Deviation 26.35 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 72 | 26.00 mm^3 | Standard Deviation 600.82 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 72 | 219.52 mm^3 | Standard Deviation 377.85 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 96 | 275.83 mm^3 | Standard Deviation 360.07 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 48 | 5.22 mm^3 | Standard Deviation 19.75 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Baseline | 91.06 mm^3 | Standard Deviation 368.98 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 96 | 330.20 mm^3 | Standard Deviation 442.02 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 24 | -120.04 mm^3 | Standard Deviation 250.42 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 72 | 56.86 mm^3 | Standard Deviation 160.83 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 96 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 48 | -146.62 mm^3 | Standard Deviation 298.86 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 48 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 96 | -391.93 mm^3 | Standard Deviation 523.92 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 72 | -155.91 mm^3 | Standard Deviation 341.97 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 24 | 3.48 mm^3 | Standard Deviation 16.7 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Baseline | 113.64 mm^3 | Standard Deviation 248.74 |
| Placebo (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 96 | -247.76 mm^3 | Standard Deviation 593.34 |
| Placebo (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Baseline | 136.61 mm^3 | Standard Deviation 344.31 |
| Placebo (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 24 | 9.14 mm^3 | Standard Deviation 55.62 |
| Placebo (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 48 | 39.00 mm^3 | Standard Deviation 188.8 |
| Placebo (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 72 | 25.85 mm^3 | Standard Deviation 96.18 |
| Placebo (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Week 96 | 22.51 mm^3 | Standard Deviation 87.17 |
| Placebo (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 24 | -134.67 mm^3 | Standard Deviation 343.19 |
| Placebo (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 48 | -116.06 mm^3 | Standard Deviation 429.9 |
| Placebo (ITP) | OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions | Change at Week 72 | -192.24 mm^3 | Standard Deviation 439.11 |
Secondary
OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions
Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
Time frame: OLMP: Baseline, Week 48 and 96
Population: OLMP Analysis Set was used. Here Number analyzed = participants evaluable at specified timepoint for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Change at Week 48 | 523.27 mm^3 | Standard Deviation 2065.54 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Week 96 | 2606.15 mm^3 | Standard Deviation 5542.81 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Baseline | 398.88 mm^3 | Standard Deviation 1102.27 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Week 48 | 767.66 mm^3 | Standard Deviation 1875.86 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Change at Week 96 | 2245.18 mm^3 | Standard Deviation 5810.53 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Week 96 | 0.00 mm^3 | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Baseline | 630.70 mm^3 | Standard Deviation 1707.24 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Week 48 | 458.13 mm^3 | Standard Deviation 984.12 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Change at Week 48 | -20.20 mm^3 | Standard Deviation 2025.21 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Change at Week 96 | 0.00 mm^3 | Standard Deviation 0 |
| Placebo (ITP) | OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Change at Week 96 | 255.39 mm^3 | Standard Deviation 1352.8 |
| Placebo (ITP) | OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Change at Week 48 | -77.67 mm^3 | Standard Deviation 1760.2 |
| Placebo (ITP) | OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Baseline | 1019.30 mm^3 | Standard Deviation 2872.03 |
| Placebo (ITP) | OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Week 96 | 647.17 mm^3 | Standard Deviation 1345.62 |
| Placebo (ITP) | OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions | Week 48 | 508.97 mm^3 | Standard Deviation 1159.97 |
Secondary
OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Number of combined unique active (CUA) lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: OLMP: Baseline, Week 24, 48, 72 and 96
Population: OLMP Analysis Set included all participants who received at least 1 dose of study drug, converted to CDMS in ITP period, entered OLMP and received at least 1 dose of OLMP study drug. Here Number of participants analyzed = participants who were evaluable for this outcome measure and Number analyzed = who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 72 | 2.45 Lesions | Standard Deviation 5.01 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 48 | 0.39 Lesions | Standard Deviation 0.81 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Baseline | 0.63 Lesions | Standard Deviation 1.17 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 24 | 0.42 Lesions | Standard Deviation 1.02 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 96 | 3.33 Lesions | Standard Deviation 6.03 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 48 | 0.38 Lesions | Standard Deviation 1.09 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Baseline | 2.17 Lesions | Standard Deviation 7.72 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 24 | 0.48 Lesions | Standard Deviation 1.4 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 72 | 0.38 Lesions | Standard Deviation 0.74 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 96 | 0.67 Lesions | Standard Deviation 1.15 |
| Placebo (ITP) | OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 96 | 0.53 Lesions | Standard Deviation 1.25 |
| Placebo (ITP) | OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 72 | 1.30 Lesions | Standard Deviation 2.71 |
| Placebo (ITP) | OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Baseline | 3.23 Lesions | Standard Deviation 8.07 |
| Placebo (ITP) | OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 48 | 0.61 Lesions | Standard Deviation 1.02 |
| Placebo (ITP) | OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions | Week 24 | 0.79 Lesions | Standard Deviation 1.33 |
Secondary
OLMP: Number of New or Enlarging T2 Lesions
Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: OLMP: Baseline, Week 24, 48, 72 and 96
Population: OLMP Analysis Set included all participants who received at least 1 dose of study drug, converted to CDMS in ITP period, entered OLMP and received at least 1 dose of OLMP study drug. Here Number of participants analyzed = participants who were evaluable for this outcome measure and Number analyzed = who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of New or Enlarging T2 Lesions | Week 72 | 0.95 Lesions | Standard Deviation 1.85 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of New or Enlarging T2 Lesions | Week 48 | 0.32 Lesions | Standard Deviation 0.65 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of New or Enlarging T2 Lesions | Baseline | 0.29 Lesions | Standard Deviation 0.75 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of New or Enlarging T2 Lesions | Week 24 | 0.26 Lesions | Standard Deviation 0.69 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of New or Enlarging T2 Lesions | Week 96 | 2.00 Lesions | Standard Deviation 3.52 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of New or Enlarging T2 Lesions | Week 48 | 0.38 Lesions | Standard Deviation 1.09 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of New or Enlarging T2 Lesions | Baseline | 1.54 Lesions | Standard Deviation 6.72 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of New or Enlarging T2 Lesions | Week 24 | 0.43 Lesions | Standard Deviation 1.35 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of New or Enlarging T2 Lesions | Week 72 | 0.25 Lesions | Standard Deviation 0.46 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of New or Enlarging T2 Lesions | Week 96 | 0.67 Lesions | Standard Deviation 1.15 |
| Placebo (ITP) | OLMP: Number of New or Enlarging T2 Lesions | Week 96 | 0.47 Lesions | Standard Deviation 1.06 |
| Placebo (ITP) | OLMP: Number of New or Enlarging T2 Lesions | Week 72 | 0.97 Lesions | Standard Deviation 1.69 |
| Placebo (ITP) | OLMP: Number of New or Enlarging T2 Lesions | Baseline | 2.13 Lesions | Standard Deviation 7.29 |
| Placebo (ITP) | OLMP: Number of New or Enlarging T2 Lesions | Week 48 | 0.41 Lesions | Standard Deviation 0.71 |
| Placebo (ITP) | OLMP: Number of New or Enlarging T2 Lesions | Week 24 | 0.68 Lesions | Standard Deviation 1.1 |
Secondary
OLMP: Number of New or Persisting Gd-enhanced Lesions
Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: OLMP: Baseline, Week 24, 48, 72 and 96
Population: OLMP Analysis Set included all participants who received at least 1 dose of study drug, converted to CDMS in ITP period, entered OLMP and received at least 1 dose of OLMP study drug. Here Number of participants analyzed = participants who were evaluable for this outcome measure and Number analyzed = who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of New or Persisting Gd-enhanced Lesions | Week 72 | 1.50 Lesions | Standard Deviation 3.28 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of New or Persisting Gd-enhanced Lesions | Week 48 | 0.07 Lesions | Standard Deviation 0.24 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of New or Persisting Gd-enhanced Lesions | Baseline | 1.38 Lesions | Standard Deviation 5.52 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of New or Persisting Gd-enhanced Lesions | Week 24 | 0.17 Lesions | Standard Deviation 0.48 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of New or Persisting Gd-enhanced Lesions | Week 96 | 1.58 Lesions | Standard Deviation 2.69 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of New or Persisting Gd-enhanced Lesions | Week 48 | 0.00 Lesions | Standard Deviation 0 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of New or Persisting Gd-enhanced Lesions | Baseline | 0.88 Lesions | Standard Deviation 1.8 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of New or Persisting Gd-enhanced Lesions | Week 24 | 0.05 Lesions | Standard Deviation 0.21 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of New or Persisting Gd-enhanced Lesions | Week 72 | 0.13 Lesions | Standard Deviation 0.35 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of New or Persisting Gd-enhanced Lesions | Week 96 | 0.00 Lesions | Standard Deviation 0 |
| Placebo (ITP) | OLMP: Number of New or Persisting Gd-enhanced Lesions | Week 96 | 0.07 Lesions | Standard Deviation 0.26 |
| Placebo (ITP) | OLMP: Number of New or Persisting Gd-enhanced Lesions | Week 72 | 0.33 Lesions | Standard Deviation 1.18 |
| Placebo (ITP) | OLMP: Number of New or Persisting Gd-enhanced Lesions | Baseline | 1.27 Lesions | Standard Deviation 2.58 |
| Placebo (ITP) | OLMP: Number of New or Persisting Gd-enhanced Lesions | Week 48 | 0.20 Lesions | Standard Deviation 0.5 |
| Placebo (ITP) | OLMP: Number of New or Persisting Gd-enhanced Lesions | Week 24 | 0.11 Lesions | Standard Deviation 0.56 |
Secondary
OLMP: Number of Relapses
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Time frame: Baseline up to Week 96
Population: OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of Relapses | 0.33 Relapses | Standard Deviation 0.64 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of Relapses | 0.16 Relapses | Standard Deviation 0.37 |
| Placebo (ITP) | OLMP: Number of Relapses | 0.55 Relapses | Standard Deviation 1 |
Secondary
OLMP: Number of T1 Hypointense Lesions
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
Time frame: OLMP: Baseline, Week 48 and 96
Population: OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif). Here Number analyzed = participants evaluable at specified timepoint for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of T1 Hypointense Lesions | Baseline | 0.92 Lesions | Standard Deviation 2.22 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of T1 Hypointense Lesions | Week 96 | 0.50 Lesions | Standard Deviation 0.84 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Number of T1 Hypointense Lesions | Week 48 | 3.79 Lesions | Standard Deviation 8.32 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of T1 Hypointense Lesions | Baseline | 2.32 Lesions | Standard Deviation 9.52 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of T1 Hypointense Lesions | Week 48 | 1.00 Lesions | Standard Deviation 2.85 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Number of T1 Hypointense Lesions | Week 96 | 0.00 Lesions | Standard Deviation 0 |
| Placebo (ITP) | OLMP: Number of T1 Hypointense Lesions | Baseline | 1.45 Lesions | Standard Deviation 3.53 |
| Placebo (ITP) | OLMP: Number of T1 Hypointense Lesions | Week 96 | 1.47 Lesions | Standard Deviation 2.8 |
| Placebo (ITP) | OLMP: Number of T1 Hypointense Lesions | Week 48 | 0.74 Lesions | Standard Deviation 1.83 |
Secondary
OLMP: Percentage of Participants With no New or Enlarging T2 Lesions
T2 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or enlarging T2 Lesions were reported.
Time frame: OLMP: Baseline up to 96
Population: OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | OLMP: Percentage of Participants With no New or Enlarging T2 Lesions | 18.2 Percentage of participants |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Percentage of Participants With no New or Enlarging T2 Lesions | 16.7 Percentage of participants |
| Placebo (ITP) | OLMP: Percentage of Participants With no New or Enlarging T2 Lesions | 13.5 Percentage of participants |
Secondary
OLMP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
Time frame: OLMP: Baseline up to Week 96
Population: OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | OLMP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions | 25.0 Percentage of participants |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions | 50.0 Percentage of participants |
| Placebo (ITP) | OLMP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions | 35.3 Percentage of participants |
Secondary
OLMP: Percentage of Relapse-Free Participants
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of relapse-free participants were reported.
Time frame: Baseline up to Week 96
Population: OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif). Here Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | OLMP: Percentage of Relapse-Free Participants | 40.0 Percentage of participants |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Percentage of Relapse-Free Participants | 20.0 Percentage of participants |
| Placebo (ITP) | OLMP: Percentage of Relapse-Free Participants | 30.8 Percentage of participants |
Secondary
OLMP: Percent Change From Baseline in Brain Volume
Brain volume was measured by using magnetic resonance imaging (MRI) scans. Percent change from baseline in brain volume at Week 48 and 96 was reported.
Time frame: OLMP: Baseline, Week 48 and 96
Population: OLMP Analysis Set was used. Here Number of participants analyzed signifies those participants who were evaluable for this outcome measure and Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | OLMP: Percent Change From Baseline in Brain Volume | Week 48 | -0.41 Percent change | Standard Deviation 0.98 |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Percent Change From Baseline in Brain Volume | Week 96 | 0.06 Percent change | Standard Deviation 1.36 |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Percent Change From Baseline in Brain Volume | Week 48 | -1.60 Percent change | Standard Deviation 1.4 |
| Placebo (ITP) | OLMP: Percent Change From Baseline in Brain Volume | Week 48 | -0.56 Percent change | Standard Deviation 1.11 |
| Placebo (ITP) | OLMP: Percent Change From Baseline in Brain Volume | Week 96 | -1.31 Percent change | Standard Deviation 0.76 |
Secondary
OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression
EDSS progression is based on a standardized neurological exam and focuses on symptoms that commonly occur in Multiple Sclerosis (MS). Overall scores ranges from 0.0 (normal) to 10.0 (death due to MS). A sustained progression on EDSS score was defined as an EDSS progression confirmed into two consecutive assessment. Probability of disability progression at different time points was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first EDSS increase.
Time frame: OLMP: Day 1, 90, 180, 270, 360, 450, 540, 630, 720 and 810
Population: OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif). Here Number analyzed signifies those participants who were evaluable at specified time point for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cladribine 5.25 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 540 | 0.0417 Probability of Disability Progression |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 630 | 0.0417 Probability of Disability Progression |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 180 | 0.0417 Probability of Disability Progression |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 720 | 0.0417 Probability of Disability Progression |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 1 | 0.0000 Probability of Disability Progression |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 270 | 0.0417 Probability of Disability Progression |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 360 | 0.0417 Probability of Disability Progression |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 90 | 0.0000 Probability of Disability Progression |
| Cladribine 5.25 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 450 | 0.0417 Probability of Disability Progression |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 360 | 0.0417 Probability of Disability Progression |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 540 | 0.0417 Probability of Disability Progression |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 1 | 0.0000 Probability of Disability Progression |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 450 | 0.0417 Probability of Disability Progression |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 630 | 0.0417 Probability of Disability Progression |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 270 | 0.0417 Probability of Disability Progression |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 90 | 0.0000 Probability of Disability Progression |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 720 | 0.0417 Probability of Disability Progression |
| Cladribine 3.5 mg/kg (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 180 | 0.0417 Probability of Disability Progression |
| Placebo (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 720 | 0.1094 Probability of Disability Progression |
| Placebo (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 1 | 0.0000 Probability of Disability Progression |
| Placebo (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 90 | 0.0000 Probability of Disability Progression |
| Placebo (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 180 | 0.0527 Probability of Disability Progression |
| Placebo (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 360 | 0.0527 Probability of Disability Progression |
| Placebo (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 450 | 0.0764 Probability of Disability Progression |
| Placebo (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 540 | 0.1094 Probability of Disability Progression |
| Placebo (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 630 | 0.1094 Probability of Disability Progression |
| Placebo (ITP) | OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression | Day 270 | 0.0527 Probability of Disability Progression |