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Oral Cladribine in Early Multiple Sclerosis (MS) (ORACLE MS)

Primary Purpose

Multiple Sclerosis

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Cladribine

Placebo

Rebif® new formulation (RNF)

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring Clinically Isolated Syndrome (CIS), Early MS, Multiple Sclerosis

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Hope Research Institute Medical Plaza LLC Desert Hills
Multiple Sclerosis Center Drive, Neurology Suite 701
University of Colorado at Denver Health Sciences
Fort Collins Neurology
MS Center of Brevard MIMA Centry Research Associates
University of South Florida
MS Center of Atlanta
Bruce Hughes West Building
Michigan Neurology Associates
Henry Ford Hospital
University of Minnesota
Dennis Dietrich
University of Medicine and Dentistry of New Jersey School of Neurology
Upstate Clinical Research LLC 3
Neurological Specialists of Long Island
Multiple Sclerosis Center of Northeastern NY
Comprehensive MS Care Clinic at South Shore Multiple Sclerosis
Carolinas Medical Center
Meritcare Neuroscience Center Neurology
University of Cincinnati
MS Center of Oklahoma
Neurology and Sleep Medicine
Swedish Medical Center Cherry Hill
Neurology & Neurological Association of Tacoma
Instituto Medico Rodriguez Alfici
Fundacion Rosarina de Neurorehabilitacion
Krankenhaus der Barmherzigen Brüder
Algemeen Ziekenhuis St Jan
Cliniques Universitaires St-Luc
Hopital Erasme
CHU de Liege - Domaine Universitaire du Sart Tilman,
Clinical Center University of Sarajevo
Military Medical Academy- Sofia (MMA)
MBAL Rousse AD 1st
Central Clinic Hospital
Military Medical Academy
National Heart Hospital
Second MHAT
Tokuda Hospital
University Hospital St Naum
Medical Centre Centromed 2000
Ottawa General Hospital
General Hospital Varazdin
University Hospital Zagreb
Faculty Hospital Brno
Neurological dept of Faculty
Fakultní nemocnice s poliklinikou Ostrava
Faculty Hospital Motol
Klinika Vseobecne
Nemocnice Teplice
East Tallinn Central Hospital
West Tallinn Central Hospital
HUS Hyvinkaa Central Hospital
OYKS Neurologian Klinikka
Neurologian Klinikka Seinajoen Keskussairaala
Tampere University Hospital
Turun Yliopistollinen Keskussairaala Rakennus 3 1
CHU de Lille
CHU de Nantes
American Memorial Hospital
David Tatishvili Medical Center
Medical Center Health
S. Khechinashvili Tbilisi State Medical University
Universitaetsklinikum und Medizinische Fakultaet Heidelberg
Philipps-Universitaet Marburg
M S Ramaiah Medical College Hospital
St.John's Medical College and Hospital
Amrita Institute of Medical Sciences and Research
Kovai Medical Centre and Hospital
Sanjay Gandhi Post Graduate Institute of Medical Sciences
Mallikatta Neuro and Research Centre
Ospedale Regionale Torrette
Università de Bari
Ospedale Binaghi Centro Sclerosi Multipla
Azienda Ospedaliera Garibaldi
Dipartimento di Neuroscienze
Università G. D'Annunzio
Ospedale San Antonio Abate
Universita degli Studi di Genova
Ospedale e casa di riposo P. Richiedei
Ospedale San Raffaele
Dipartimento di Scienze Neurologiche
Azienda Sanitaria Ospedaliera San Luigi Gonzaga
Villa Sofia Hospital Azienda Ospedaliera Villa Sofia P.zza Salerno e Resuttana 1
Istituto Neurologico C. Mondino
Azienda Ospedaliera S. Camillo Forlanini
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Università di Roma La Sapienza
National Cancer Center, Department of Neurology,
Department of Neurology, 50 Ilwon-dong, Gangnam-gu
Department of Neurology, Asan Medical Center, 388-1 Pungnap 2-dong, Songpa-gu
Seoul National University Hospital, Department of Neurology
Yonsei University Medical Center, Department of Neurology, Yonsei University Medical Center
American University of Beirut
Clinic of Neurology "Klinicki Centar"
Helse Bergen HF Kvinneklinikken Haukeland Universitetssykehus Jonas
Regionsykehuset I Trondheim, Nevrologisk avd.
10 Wojskowy Szpital Kliniczny
Wojewodzki Szpital Specjalistyczny im. M. Kopernika
Niepubliczny Zespol Opieki Zdrowotnej
Medical Academy of Lodz
Panstwowy Szpital Kliniczny
Wojewodzki Szpital Specjalistyczny Oddział Neurologii z Pododdziałem Udarowym
Medical Academy
Medical Academy II
Medical Academy
Hospital Fernando da Fonseca
Hospitais da Universidade de Coimbra
Hospital de Santa Maria
Centro Hospitalar de Coimbra
"Dr. Carol Davilla" Military Clinical Hospital
Centrul Medical SANA
Spitalul Clinic Judetean Mures
County Hospital Timisoara
Municipal Healthcare Institution "City Clinical Hospital #3"
State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1"
State Healthcare Institution "Kaluga Regional Hospital"
State Medical Institution "Republican Rehabilitation Clinic of Tatarstan Ministry of Health"
State Healthcare Institution "Kemerovo Regional Clinical Hospital"
State Medical Institution " Jursk Regional Clinical Hospital"
Moscow State Healthcare Institution City Clinical Hospital #11
Non-State Healthcare Institution "Central Clinical Hospital #2 named after N.A. Semasko of Russian Railways"
State Educational Institute of Higher Professional Education "I.M. Sechenov Moscow Medical Academy of Roszdrav" Russia based on A. Ya. Kozhevnikov Nervous Disease Clinic
Municipal Treatment Prophylactic Institution "City Hospital #33"
Federal State Institution " Siberian Reginal Medical Center of Roszdarv"
State institution Science Research Institute Clinical and Experimental Lymphology of Russian Academy of Medical Sciences
State Educational Institute of Higher Professional Education "Rostov State Medical University of Roszdrav"
State Healthcare Institution "Rostov Region Clinical Hospital"
State Educational Institution of Higher Professional Education "Military Medical Academy named after S. M. Korov of Dept of Defense of Russian Federation based on Clinic of Neurology of State Institution
State Educational Institution of Higher Professional Education "Samara State Medical University of Roszdrav" on State Healthcare Institution "Samara Regional Clinical Hospital named after M. I. Kalinin"
State Educational Institution of Higher Professional Education "Saratov State Medical University of Roszdrav" based on Clincial Hosptial #3 of Saratov State Medical University
Regional State Healthcare Institution "State Smolensk Region Clinical Hospital"
Institute of Human Brain of Russian Academy of Science Dept. of Multiple Sclerosis
International Clinic and Hospital, Neurology
St. Petersburg State Healthcare Institution "Multifield City Hospital #2"
State Educational Institution of Higher Professional Education "Siberian State Medical University of Roszdrav"
Closed joint-stock society Medical sanitary unit "Nephtaynik" based the hospital
Vladimir Regional State Healthcare Institution "Regional Clinical Hospital"
Municipal Healthcare Institution "Yaroslavi Clinical Hospital #8"
Clinical Centre of Serbia
Hospital for Prevention and Treatment of Cerebro-Vascular Diseases
Clinical Centre Niš
National Neuroscience Institute (TTSH Campus)
Hospital Reina Sofia Cordoba
Hospital Universitario Nuestra Senora de la Candelaria
Sahlgrenskasjukhuset
Karolinska University Hospital
Umea University Hospital
Taipei Veterans
Chang Gung Medical Foundation- Linkou Branch No5
Srinagarind Hospital
Dokuz Eylul University
Ondokuz Mayis Universitesi
State Established "Institute of Neurology, Psychiatry and Narcology of the AMS of Ukraine", Depart of Neurinfections and Multiple Sclorosis
Institue for Clinical Radiology of the State Establishment "Research Centre for Radiation Medicine of the AMS of Ukraino" Depart of Radiation Psychoneurology
Vinnylsia Regional Psychoneurological Hosptial Named After O. I Yushchenko, Neurological Depart, Vinnytsia National Medical University Named After M. I. Pirogov, Chair of Neurology
Rashid Hospital
Kings College London

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Cladribine 5.25 mg/kg (ITP)

Cladribine 3.5 mg/kg (ITP)

Placebo (ITP)

Cladribine 5.25 mg/kg, Rebif (OLMP)

Cladribine 3.5 mg/kg, Rebif (OLMP)

Placebo, Rebif (OLMP)

Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)

Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)

Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)

Cladribine 5.25 mg/kg, Rebif (LTFU)

Cladribine 3.5 mg/kg, Rebif (LTFU)

Placebo, Rebif (LTFU)

Arm Description

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 milligrams per kilograms (mg/kg) during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.

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.

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 received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.

Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.

Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.

Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) 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. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.

Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) 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. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.

Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) 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. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.

Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in 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 period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.

Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in 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 period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.

Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Multiple Sclerosis (MS) According to the 2005 McDonald Criteria

LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria

LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria

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.

ITP: Percentage of Participants Converting to McDonald Multiple Sclerosis (MS) (2005)

Percentage of participants converting to mcDonald multiple sclerosis (2005) were reported.

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.

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.

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.

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.

ITP: Number of New or Enlarging T2 Lesions

Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.

OLMP: Number of New or Enlarging T2 Lesions

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

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

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

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

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

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

Number of CUA lesions were measured by using magnetic resonance imaging (MRI) scans.

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.

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.

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.

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.

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.

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.

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.

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.

ITP: Number of T1 Hypointense Lesions

Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.

OLMP: Number of T1 Hypointense Lesions

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

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

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

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

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

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

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

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

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

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

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

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.

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.

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.

LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Relapses

LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Relapses

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.

OLMP: Percentage of Relapse-Free Participants

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.

Full Information

NCT ID

NCT00725985

First Posted

July 30, 2008

Last Updated

February 24, 2021

Sponsor

EMD Serono Research & Development Institute, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00725985

Brief Title

Oral Cladribine in Early Multiple Sclerosis (MS)

Acronym

ORACLE MS

Official Title

A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center Clinical Trial of Oral Cladribine in Subjects With a First Clinical Event at High Risk of Converting to MS

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Completed

Study Start Date

December 31, 2008 (Actual)

Primary Completion Date

July 31, 2011 (Actual)

Study Completion Date

April 30, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

EMD Serono Research & Development Institute, Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis

Keywords

Clinically Isolated Syndrome (CIS), Early MS, Multiple Sclerosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

617 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cladribine 5.25 mg/kg (ITP)

Arm Type

Experimental

Arm Description

Arm Title

Cladribine 3.5 mg/kg (ITP)

Arm Type

Experimental

Arm Description

Arm Title

Placebo (ITP)

Arm Type

Placebo Comparator

Arm Description

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.

Arm Title

Cladribine 5.25 mg/kg, Rebif (OLMP)

Arm Type

Experimental

Arm Description

Arm Title

Cladribine 3.5 mg/kg, Rebif (OLMP)

Arm Type

Experimental

Arm Description

Arm Title

Placebo, Rebif (OLMP)

Arm Type

Experimental

Arm Description

Arm Title

Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)

Arm Type

Experimental

Arm Description

Arm Title

Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)

Arm Type

Experimental

Arm Description

Arm Title

Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)

Arm Type

Experimental

Arm Description

Arm Title

Cladribine 5.25 mg/kg, Rebif (LTFU)

Arm Type

Experimental

Arm Description

Arm Title

Cladribine 3.5 mg/kg, Rebif (LTFU)

Arm Type

Experimental

Arm Description

Arm Title

Placebo, Rebif (LTFU)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cladribine

Intervention Description

Cladribine tablets were administered until CDMS conversion, whichever occur first.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo matched to cladribine tablets were administered.

Intervention Type

Drug

Intervention Name(s)

Rebif® new formulation (RNF)

Intervention Description

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.

Primary Outcome Measure Information:

Title

ITP: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS

Description

Time Frame

ITP: Baseline up to Week 96

Secondary Outcome Measure Information:

Title

Description

Time Frame

ITP: Baseline up to Week 96

Title

Description

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

Title

OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression

Description

Time Frame

OLMP: Day 1, 90, 180, 270, 360, 450, 540, 630, 720 and 810

Title

LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Multiple Sclerosis (MS) According to the 2005 McDonald Criteria

Description

Time Frame

Time from Randomization up to 1217 days

Title

LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria

Description

Time Frame

Time from Randomization up to 1217 days

Title

LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria

Description

Time Frame

Time from Randomization up to 1217 days

Title

ITP: Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) as Per Poser Criteria

Description

Time Frame

ITP: Baseline up to week 96

Title

ITP: Percentage of Participants Converting to McDonald Multiple Sclerosis (MS) (2005)

Description

Percentage of participants converting to mcDonald multiple sclerosis (2005) were reported.

Time Frame

ITP: Baseline up to week 96

Title

ITP: Number of New or Persisting Gd-enhanced Lesions

Description

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

Title

OLMP: Number of New or Persisting Gd-enhanced Lesions

Description

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

Title

LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions

Description

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

Title

LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions

Description

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

Title

ITP: Number of New or Enlarging T2 Lesions

Description

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

Title

OLMP: Number of New or Enlarging T2 Lesions

Description

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

Title

LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions

Description

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

Title

LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions

Description

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

Title

ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions

Description

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

Title

OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions

Description

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

Title

LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions

Description

Number of CUA MRI lesions were measured by using magnetic resonance imaging (MRI) scans.

Time Frame

LTFU: Baseline, Week 13, 24 and 36

Title

LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions

Description

Number of CUA lesions were measured by using magnetic resonance imaging (MRI) scans.

Time Frame

LTFU: Baseline, Week 13, 24, 36 and 48

Title

ITP: Change From Baseline in Volume of T1 Gd-Enhanced Lesions

Description

Change in volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.

Time Frame

ITP: Baseline, Week 96

Title

OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions

Description

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

Title

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

Description

Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.

Time Frame

LTFU: Baseline, Week 13, 24 and 36

Title

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

Description

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

Title

ITP: Changes From Baseline in Volume of T2 Lesions

Description

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

Title

OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions

Description

Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.

Time Frame

OLMP: Baseline, Week 48 and 96

Title

LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T2 Lesions

Description

Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.

Time Frame

LTFU: Baseline (Day 1)

Title

LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions

Description

Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.

Time Frame

Baseline, Week 48

Title

ITP: Number of T1 Hypointense Lesions

Description

Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.

Time Frame

ITP: Baseline, Week 48 and 96

Title

OLMP: Number of T1 Hypointense Lesions

Description

Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.

Time Frame

OLMP: Baseline, Week 48 and 96

Title

LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of T1 Hypointense Lesions

Description

Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.

Time Frame

LTFU: Baseline (Day 1)

Title

LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of T1 Hypointense Lesions

Description

Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.

Time Frame

LTFU: Baseline, Week 48

Title

ITP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions

Description

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

Title

OLMP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions

Description

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

Title

LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions

Description

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

Title

LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions

Description

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

Title

ITP: Percentage of Participants With no New or Enlarging T2 Lesions

Description

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

Title

OLMP: Percentage of Participants With no New or Enlarging T2 Lesions

Description

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

Title

LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions

Description

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

Title

LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions

Description

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

Title

ITP: Percent Change From Baseline in Brain Volume

Description

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

Title

OLMP: Percent Change From Baseline in Brain Volume

Description

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

Title

OLMP: Number of Relapses

Description

Time Frame

Baseline up to Week 96

Title

LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Relapses

Description

Time Frame

Baseline up to Week 48

Title

LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Relapses

Description

Time Frame

Baseline up to Week 48

Title

OLMP: Annualized Relapse Rate

Description

Time Frame

Baseline up to Week 96

Title

OLMP: Percentage of Relapse-Free Participants

Description

Time Frame

Baseline up to Week 96

Title

ITP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

Description

Time Frame

ITP: Baseline up to Week 96

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bettina Stubinski, MD

Organizational Affiliation

Merck Serono S.A., Geneva

Official's Role

Study Director

Facility Information:

Facility Name

Hope Research Institute Medical Plaza LLC Desert Hills

City

Phoenix

State/Province

Arizona

Country

United States

Facility Name

Multiple Sclerosis Center Drive, Neurology Suite 701

City

Newport Beach

State/Province

California

Country

United States

Facility Name

University of Colorado at Denver Health Sciences

City

Denver

State/Province

Colorado

Country

United States

Facility Name

Fort Collins Neurology

City

Fort Collins

State/Province

Colorado

Country

United States

Facility Name

MS Center of Brevard MIMA Centry Research Associates

City

Melbourne

State/Province

Florida

Country

United States

Facility Name

University of South Florida

City

Tampa

State/Province

Florida

Country

United States

Facility Name

MS Center of Atlanta

City

Atlanta

State/Province

Georgia

Country

United States

Facility Name

Bruce Hughes West Building

City

Des Moines

State/Province

Iowa

Country

United States

Facility Name

Michigan Neurology Associates

City

Clinton Township

State/Province

Michigan

Country

United States

Facility Name

Henry Ford Hospital

City

Detroit

State/Province

Michigan

Country

United States

Facility Name

University of Minnesota

City

Minneapolis

State/Province

Minnesota

Country

United States

Facility Name

Dennis Dietrich

City

Great Falls

State/Province

Montana

Country

United States

Facility Name

University of Medicine and Dentistry of New Jersey School of Neurology

City

Stratford

State/Province

New Jersey

Country

United States

Facility Name

Upstate Clinical Research LLC 3

City

Albany

State/Province

New York

Country

United States

Facility Name

Neurological Specialists of Long Island

City

Great Neck

State/Province

New York

Country

United States

Facility Name

Multiple Sclerosis Center of Northeastern NY

City

New York

State/Province

New York

Country

United States

Facility Name

Comprehensive MS Care Clinic at South Shore Multiple Sclerosis

City

Patchogue

State/Province

New York

Country

United States

Facility Name

Carolinas Medical Center

City

Charlotte

State/Province

North Carolina

Country

United States

Facility Name

Meritcare Neuroscience Center Neurology

City

Fargo

State/Province

North Dakota

Country

United States

Facility Name

University of Cincinnati

City

Cincinnati

State/Province

Ohio

Country

United States

Facility Name

MS Center of Oklahoma

City

Oklahoma City

State/Province

Oklahoma

Country

United States

Facility Name

Neurology and Sleep Medicine

City

Bethlehem

State/Province

Pennsylvania

Country

United States

Facility Name

Swedish Medical Center Cherry Hill

City

Seattle

State/Province

Washington

Country

United States

Facility Name

Neurology & Neurological Association of Tacoma

City

Tacoma

State/Province

Washington

Country

United States

Facility Name

Instituto Medico Rodriguez Alfici

City

Godoy Cruz

Country

Argentina

Facility Name

Fundacion Rosarina de Neurorehabilitacion

City

Rosario

Country

Argentina

Facility Name

Krankenhaus der Barmherzigen Brüder

City

Linz

Country

Austria

Facility Name

Algemeen Ziekenhuis St Jan

City

Brugge

Country

Belgium

Facility Name

Cliniques Universitaires St-Luc

City

Brussels

Country

Belgium

Facility Name

Hopital Erasme

City

Bruxelles

Country

Belgium

Facility Name

CHU de Liege - Domaine Universitaire du Sart Tilman,

City

Liège

Country

Belgium

Facility Name

Clinical Center University of Sarajevo

City

Sarajevo

Country

Bosnia and Herzegovina

Facility Name

Military Medical Academy- Sofia (MMA)

City

Pleven

Country

Bulgaria

Facility Name

MBAL Rousse AD 1st

City

Rousse

Country

Bulgaria

Facility Name

Central Clinic Hospital

City

Sofia

Country

Bulgaria

Facility Name

Military Medical Academy

City

Sofia

Country

Bulgaria

Facility Name

National Heart Hospital

City

Sofia

Country

Bulgaria

Facility Name

Second MHAT

City

Sofia

Country

Bulgaria

Facility Name

Tokuda Hospital

City

Sofia

Country

Bulgaria

Facility Name

University Hospital St Naum

City

Sofia

Country

Bulgaria

Facility Name

Medical Centre Centromed 2000

City

Veliko Tarnovo

Country

Bulgaria

Facility Name

Ottawa General Hospital

City

Ottawa

Country

Canada

Facility Name

General Hospital Varazdin

City

Varazdin

Country

Croatia

Facility Name

University Hospital Zagreb

City

Zagreb

Country

Croatia

Facility Name

Faculty Hospital Brno

City

Brno

Country

Czechia

Facility Name

Neurological dept of Faculty

City

Hradec Kralove

Country

Czechia

Facility Name

Fakultní nemocnice s poliklinikou Ostrava

City

Ostrava

Country

Czechia

Facility Name

Faculty Hospital Motol

City

Prague

Country

Czechia

Facility Name

Klinika Vseobecne

City

Prague

Country

Czechia

Facility Name

Nemocnice Teplice

City

Teplice

Country

Czechia

Facility Name

East Tallinn Central Hospital

City

Tallinn

Country

Estonia

Facility Name

West Tallinn Central Hospital

City

Tallinn

Country

Estonia

Facility Name

HUS Hyvinkaa Central Hospital

City

Hyvinkaa

Country

Finland

Facility Name

OYKS Neurologian Klinikka

City

Oulu

Country

Finland

Facility Name

Neurologian Klinikka Seinajoen Keskussairaala

City

Seinajoki

Country

Finland

Facility Name

Tampere University Hospital

City

Tampere

Country

Finland

Facility Name

Turun Yliopistollinen Keskussairaala Rakennus 3 1

City

Turku

Country

Finland

Facility Name

CHU de Lille

City

Lille Cedex

Country

France

Facility Name

CHU de Nantes

City

Nantes

Country

France

Facility Name

American Memorial Hospital

City

Reims Cedex

Country

France

Facility Name

David Tatishvili Medical Center

City

Tbilisi

Country

Georgia

Facility Name

Medical Center Health

City

Tbilisi

Country

Georgia

Facility Name

S. Khechinashvili Tbilisi State Medical University

City

Tbilisi

Country

Georgia

Facility Name

Universitaetsklinikum und Medizinische Fakultaet Heidelberg

City

Heidelberg

Country

Germany

Facility Name

Philipps-Universitaet Marburg

City

Marburg

Country

Germany

Facility Name

M S Ramaiah Medical College Hospital

City

Bangalore

State/Province

Karnataka

Country

India

Facility Name

St.John's Medical College and Hospital

City

Bangalore

State/Province

Karnataka

Country

India

Facility Name

Amrita Institute of Medical Sciences and Research

City

Kochi

State/Province

Kerala

Country

India

Facility Name

Kovai Medical Centre and Hospital

City

Coimbatore

Country

India

Facility Name

Sanjay Gandhi Post Graduate Institute of Medical Sciences

City

Lucknow

Country

India

Facility Name

Mallikatta Neuro and Research Centre

City

Mangalore

Country

India

Facility Name

Ospedale Regionale Torrette

City

Ancona

Country

Italy

Facility Name

Università de Bari

City

Bari

Country

Italy

Facility Name

Ospedale Binaghi Centro Sclerosi Multipla

City

Cagliari

Country

Italy

Facility Name

Azienda Ospedaliera Garibaldi

City

Catania

Country

Italy

Facility Name

Dipartimento di Neuroscienze

City

Catania

Country

Italy

Facility Name

Università G. D'Annunzio

City

Chieti

Country

Italy

Facility Name

Ospedale San Antonio Abate

City

Gallarate

Country

Italy

Facility Name

Universita degli Studi di Genova

City

Genova

Country

Italy

Facility Name

Ospedale e casa di riposo P. Richiedei

City

Gussago

Country

Italy

Facility Name

Ospedale San Raffaele

City

Milano

Country

Italy

Facility Name

Dipartimento di Scienze Neurologiche

City

Napoli

Country

Italy

Facility Name

Azienda Sanitaria Ospedaliera San Luigi Gonzaga

City

Orbassano

Country

Italy

Facility Name

Villa Sofia Hospital Azienda Ospedaliera Villa Sofia P.zza Salerno e Resuttana 1

City

Palermo

Country

Italy

Facility Name

Istituto Neurologico C. Mondino

City

Pavia

Country

Italy

Facility Name

Azienda Ospedaliera S. Camillo Forlanini

City

Roma

Country

Italy

Facility Name

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

City

Roma

Country

Italy

Facility Name

Università di Roma La Sapienza

City

Roma

Country

Italy

Facility Name

National Cancer Center, Department of Neurology,

City

Gyeonggi-do

Country

Korea, Republic of

Facility Name

Department of Neurology, 50 Ilwon-dong, Gangnam-gu

City

Seoul

Country

Korea, Republic of

Facility Name

Department of Neurology, Asan Medical Center, 388-1 Pungnap 2-dong, Songpa-gu

City

Seoul

Country

Korea, Republic of

Facility Name

Seoul National University Hospital, Department of Neurology

City

Seoul

Country

Korea, Republic of

Facility Name

Yonsei University Medical Center, Department of Neurology, Yonsei University Medical Center

City

Seoul

Country

Korea, Republic of

Facility Name

American University of Beirut

City

Beirut

Country

Lebanon

Facility Name

Clinic of Neurology "Klinicki Centar"

City

Skopje

Country

North Macedonia

Facility Name

Helse Bergen HF Kvinneklinikken Haukeland Universitetssykehus Jonas

City

Bergen

Country

Norway

Facility Name

Regionsykehuset I Trondheim, Nevrologisk avd.

City

Trondheim

Country

Norway

Facility Name

10 Wojskowy Szpital Kliniczny

City

Bydgoszcz

Country

Poland

Facility Name

Wojewodzki Szpital Specjalistyczny im. M. Kopernika

City

Gdansk

Country

Poland

Facility Name

Niepubliczny Zespol Opieki Zdrowotnej

City

Krakow

Country

Poland

Facility Name

Medical Academy of Lodz

City

Lodz

Country

Poland

Facility Name

Panstwowy Szpital Kliniczny

City

Lublin

Country

Poland

Facility Name

Wojewodzki Szpital Specjalistyczny Oddział Neurologii z Pododdziałem Udarowym

City

Olsztyn

Country

Poland

Facility Name

Medical Academy

City

Poznan

Country

Poland

Facility Name

Medical Academy II

City

Warsaw

Country

Poland

Facility Name

Medical Academy

City

Warsaw

Country

Poland

Facility Name

Hospital Fernando da Fonseca

City

Amadora

Country

Portugal

Facility Name

Hospitais da Universidade de Coimbra

City

Coimbra

Country

Portugal

Facility Name

Hospital de Santa Maria

City

Lisboa

Country

Portugal

Facility Name

Centro Hospitalar de Coimbra

City

S. Martinho Do Bispo

Country

Portugal

Facility Name

"Dr. Carol Davilla" Military Clinical Hospital

City

Bucharest

Country

Romania

Facility Name

Centrul Medical SANA

City

Bucharest

Country

Romania

Facility Name

Spitalul Clinic Judetean Mures

City

Targu-Mures

Country

Romania

Facility Name

County Hospital Timisoara

City

Timisoara

Country

Romania

Facility Name

Municipal Healthcare Institution "City Clinical Hospital #3"

City

Chelyabinsk

Country

Russian Federation

Facility Name

State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1"

City

Ekaterinburg

Country

Russian Federation

Facility Name

State Healthcare Institution "Kaluga Regional Hospital"

City

Kaluga

Country

Russian Federation

Facility Name

State Medical Institution "Republican Rehabilitation Clinic of Tatarstan Ministry of Health"

City

Kazan

Country

Russian Federation

Facility Name

State Healthcare Institution "Kemerovo Regional Clinical Hospital"

City

Kemerovo

Country

Russian Federation

Facility Name

State Medical Institution " Jursk Regional Clinical Hospital"

City

Kursk

Country

Russian Federation

Facility Name

Moscow State Healthcare Institution City Clinical Hospital #11

City

Moscow

Country

Russian Federation

Facility Name

Non-State Healthcare Institution "Central Clinical Hospital #2 named after N.A. Semasko of Russian Railways"

City

Moscow

Country

Russian Federation

Facility Name

State Educational Institute of Higher Professional Education "I.M. Sechenov Moscow Medical Academy of Roszdrav" Russia based on A. Ya. Kozhevnikov Nervous Disease Clinic

City

Moscow

Country

Russian Federation

Facility Name

Municipal Treatment Prophylactic Institution "City Hospital #33"

City

Nizhny Novgorod

Country

Russian Federation

Facility Name

Federal State Institution " Siberian Reginal Medical Center of Roszdarv"

City

Novosibirsk

Country

Russian Federation

Facility Name

State institution Science Research Institute Clinical and Experimental Lymphology of Russian Academy of Medical Sciences

City

Novosibirsk

Country

Russian Federation

Facility Name

State Educational Institute of Higher Professional Education "Rostov State Medical University of Roszdrav"

City

Rostov-on-Don

Country

Russian Federation

Facility Name

State Healthcare Institution "Rostov Region Clinical Hospital"

City

Rostov-on-Don

Country

Russian Federation

Facility Name

State Educational Institution of Higher Professional Education "Military Medical Academy named after S. M. Korov of Dept of Defense of Russian Federation based on Clinic of Neurology of State Institution

City

Saint-Petersburg

Country

Russian Federation

Facility Name

State Educational Institution of Higher Professional Education "Samara State Medical University of Roszdrav" on State Healthcare Institution "Samara Regional Clinical Hospital named after M. I. Kalinin"

City

Samara

Country

Russian Federation

Facility Name

State Educational Institution of Higher Professional Education "Saratov State Medical University of Roszdrav" based on Clincial Hosptial #3 of Saratov State Medical University

City

Saratov

Country

Russian Federation

Facility Name

Regional State Healthcare Institution "State Smolensk Region Clinical Hospital"

City

Smolensk

Country

Russian Federation

Facility Name

Institute of Human Brain of Russian Academy of Science Dept. of Multiple Sclerosis

City

St Petersburg

Country

Russian Federation

Facility Name

International Clinic and Hospital, Neurology

City

St Petersburg

Country

Russian Federation

Facility Name

St. Petersburg State Healthcare Institution "Multifield City Hospital #2"

City

St. Petersburg

Country

Russian Federation

Facility Name

State Educational Institution of Higher Professional Education "Siberian State Medical University of Roszdrav"

City

Tomsk

Country

Russian Federation

Facility Name

Closed joint-stock society Medical sanitary unit "Nephtaynik" based the hospital

City

Tyumen

Country

Russian Federation

Facility Name

Vladimir Regional State Healthcare Institution "Regional Clinical Hospital"

City

Vladimir

Country

Russian Federation

Facility Name

Municipal Healthcare Institution "Yaroslavi Clinical Hospital #8"

City

Yaroslavl

Country

Russian Federation

Facility Name

Clinical Centre of Serbia

City

Belgrade

Country

Serbia

Facility Name

Hospital for Prevention and Treatment of Cerebro-Vascular Diseases

City

Belgrade

Country

Serbia

Facility Name

Clinical Centre Niš

City

Niš

Country

Serbia

Facility Name

National Neuroscience Institute (TTSH Campus)

City

Singapore

Country

Singapore

Facility Name

Hospital Reina Sofia Cordoba

City

Cordoba

Country

Spain

Facility Name

Hospital Universitario Nuestra Senora de la Candelaria

City

Sta. Cruz de Tenerife

Country

Spain

Facility Name

Sahlgrenskasjukhuset

City

Goteborg

Country

Sweden

Facility Name

Karolinska University Hospital

City

Stockholm

Country

Sweden

Facility Name

Umea University Hospital

City

Umea

Country

Sweden

Facility Name

Taipei Veterans

City

Taipei

Country

Taiwan

Facility Name

Chang Gung Medical Foundation- Linkou Branch No5

City

Taoyuan

Country

Taiwan

Facility Name

Srinagarind Hospital

City

Khon Kaen

Country

Thailand

Facility Name

Dokuz Eylul University

City

Izmir

Country

Turkey

Facility Name

Ondokuz Mayis Universitesi

City

Samsun

Country

Turkey

Facility Name

State Established "Institute of Neurology, Psychiatry and Narcology of the AMS of Ukraine", Depart of Neurinfections and Multiple Sclorosis

City

Kharkiv

Country

Ukraine

Facility Name

Institue for Clinical Radiology of the State Establishment "Research Centre for Radiation Medicine of the AMS of Ukraino" Depart of Radiation Psychoneurology

City

Kiev

Country

Ukraine

Facility Name

Vinnylsia Regional Psychoneurological Hosptial Named After O. I Yushchenko, Neurological Depart, Vinnytsia National Medical University Named After M. I. Pirogov, Chair of Neurology

City

Vinnitsa

Country

Ukraine

Facility Name

Rashid Hospital

City

Dubai

Country

United Arab Emirates

Facility Name

Kings College London

City

London

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

35019731

Citation

Oh J, Walker B, Giovannoni G, Jack D, Dangond F, Nolting A, Aldridge J, Lebson LA, Leist TP. Side effects that occurred early in people with multiple sclerosis during the first year of treatment with cladribine tablets: a plain language summary. Neurodegener Dis Manag. 2022 Feb 1;12(1):1-7. doi: 10.2217/nmt-2021-0041. Epub 2022 Jan 12.

Results Reference

derived

PubMed Identifier

35003076

Citation

Giovannoni G, Coyle PK, Vermersch P, Walker B, Aldridge J, Nolting A, Galazka A, Lemieux C, Leist TP. Integrated Lymphopenia Analysis in Younger and Older Patients With Multiple Sclerosis Treated With Cladribine Tablets. Front Immunol. 2021 Dec 24;12:763433. doi: 10.3389/fimmu.2021.763433. eCollection 2021.

Results Reference

derived

PubMed Identifier

32447743

Citation

Giovannoni G, Galazka A, Schick R, Leist T, Comi G, Montalban X, Damian D, Dangond F, Cook S. Pregnancy Outcomes During the Clinical Development Program of Cladribine in Multiple Sclerosis: An Integrated Analysis of Safety. Drug Saf. 2020 Jul;43(7):635-643. doi: 10.1007/s40264-020-00948-x.

Results Reference

derived

PubMed Identifier

29051829

Citation

Freedman MS, Leist TP, Comi G, Cree BA, Coyle PK, Hartung HP, Vermersch P, Damian D, Dangond F. The efficacy of cladribine tablets in CIS patients retrospectively assigned the diagnosis of MS using modern criteria: Results from the ORACLE-MS study. Mult Scler J Exp Transl Clin. 2017 Oct 9;3(4):2055217317732802. doi: 10.1177/2055217317732802. eCollection 2017 Oct-Dec.

Results Reference

derived

PubMed Identifier

24502830

Citation

Leist TP, Comi G, Cree BA, Coyle PK, Freedman MS, Hartung HP, Vermersch P, Casset-Semanaz F, Scaramozza M; oral cladribine for early MS (ORACLE MS) Study Group. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol. 2014 Mar;13(3):257-67. doi: 10.1016/S1474-4422(14)70005-5. Epub 2014 Feb 4.

Results Reference

derived

Links:

URL

https://clinicaltrials.emdgroup.com/en/trial-details/?id=28821

Description

Trial Awareness and Transparency website

URL

https://medical.emdserono.com/en_US/home.html

Description

US Medical Information website, Medical Resources

Learn more about this trial

Oral Cladribine in Early Multiple Sclerosis (MS)

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