Oral Cladribine in Early Multiple Sclerosis (MS)

NCT ID: NCT00725985

Last Updated: 2021-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 617 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2012-04-30

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.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cladribine 5.25 mg/kg (ITP)

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.

Group Type: EXPERIMENTAL

Cladribine

Intervention Type: DRUG

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

Rebif® new formulation (RNF)

Intervention Type: DRUG

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.

Cladribine 3.5 mg/kg (ITP)

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.

Group Type: EXPERIMENTAL

Cladribine

Intervention Type: DRUG

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

Rebif® new formulation (RNF)

Intervention Type: DRUG

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.

Placebo (ITP)

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo matched to cladribine tablets were administered.

Rebif® new formulation (RNF)

Intervention Type: DRUG

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.

Cladribine 5.25 mg/kg, Rebif (OLMP)

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.

Group Type: EXPERIMENTAL

Cladribine

Intervention Type: DRUG

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

Rebif® new formulation (RNF)

Intervention Type: DRUG

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.

Cladribine 3.5 mg/kg, Rebif (OLMP)

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.

Group Type: EXPERIMENTAL

Cladribine

Intervention Type: DRUG

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

Rebif® new formulation (RNF)

Intervention Type: DRUG

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.

Placebo, Rebif (OLMP)

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo matched to cladribine tablets were administered.

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

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.

Group Type: EXPERIMENTAL

Cladribine

Intervention Type: DRUG

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

Rebif® new formulation (RNF)

Intervention Type: DRUG

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.

Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (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.

Group Type: EXPERIMENTAL

Cladribine

Intervention Type: DRUG

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

Rebif® new formulation (RNF)

Intervention Type: DRUG

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.

Placebo, Rebif, Cladribine 3.5 mg/kg (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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo matched to cladribine tablets were administered.

Cladribine 5.25 mg/kg, Rebif (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.

Group Type: EXPERIMENTAL

Cladribine

Intervention Type: DRUG

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

Rebif® new formulation (RNF)

Intervention Type: DRUG

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.

Cladribine 3.5 mg/kg, Rebif (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.

Group Type: EXPERIMENTAL

Cladribine

Intervention Type: DRUG

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

Rebif® new formulation (RNF)

Intervention Type: DRUG

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.

Placebo, Rebif (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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo matched to cladribine tablets were administered.

Interventions

Cladribine

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

Intervention Type: DRUG

Placebo

Placebo matched to cladribine tablets were administered.

Intervention Type: DRUG

Rebif® 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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bettina Stubinski, MD

Role: STUDY_DIRECTOR

Merck Serono S.A., Geneva

Locations

Hope Research Institute Medical Plaza LLC Desert Hills

Phoenix, Arizona, United States

Multiple Sclerosis Center Drive, Neurology Suite 701

Newport Beach, California, United States

University of Colorado at Denver Health Sciences

Denver, Colorado, United States

Fort Collins Neurology

Fort Collins, Colorado, United States

MS Center of Brevard MIMA Centry Research Associates

Melbourne, Florida, United States

University of South Florida

Tampa, Florida, United States

MS Center of Atlanta

Atlanta, Georgia, United States

Bruce Hughes West Building

Des Moines, Iowa, United States

Michigan Neurology Associates

Clinton Township, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Dennis Dietrich

Great Falls, Montana, United States

University of Medicine and Dentistry of New Jersey School of Neurology

Stratford, New Jersey, United States

Upstate Clinical Research LLC 3

Albany, New York, United States

Neurological Specialists of Long Island

Great Neck, New York, United States

Multiple Sclerosis Center of Northeastern NY

New York, New York, United States

Comprehensive MS Care Clinic at South Shore Multiple Sclerosis

Patchogue, New York, United States

Carolinas Medical Center

Charlotte, North Carolina, United States

Meritcare Neuroscience Center Neurology

Fargo, North Dakota, United States

University of Cincinnati

Cincinnati, Ohio, United States

MS Center of Oklahoma

Oklahoma City, Oklahoma, United States

Neurology and Sleep Medicine

Bethlehem, Pennsylvania, United States

Swedish Medical Center Cherry Hill

Seattle, Washington, United States

Neurology & Neurological Association of Tacoma

Tacoma, Washington, United States

Instituto Medico Rodriguez Alfici

Godoy Cruz, , Argentina

Fundacion Rosarina de Neurorehabilitacion

Rosario, , Argentina

Krankenhaus der Barmherzigen Brüder

Linz, , Austria

Algemeen Ziekenhuis St Jan

Bruges, , Belgium

Cliniques Universitaires St-Luc

Brussels, , Belgium

Hopital Erasme

Brussels, , Belgium

CHU de Liege - Domaine Universitaire du Sart Tilman,

Liège, , Belgium

Clinical Center University of Sarajevo

Sarajevo, , Bosnia and Herzegovina

Military Medical Academy- Sofia (MMA)

Pleven, , Bulgaria

MBAL Rousse AD 1st

Rousse, , Bulgaria

Central Clinic Hospital

Sofia, , Bulgaria

Military Medical Academy

Sofia, , Bulgaria

National Heart Hospital

Sofia, , Bulgaria

Second MHAT

Sofia, , Bulgaria

Tokuda Hospital

Sofia, , Bulgaria

University Hospital St Naum

Sofia, , Bulgaria

Medical Centre Centromed 2000

Veliko Tarnovo, , Bulgaria

Ottawa General Hospital

Ottawa, , Canada

General Hospital Varazdin

Varaždin, , Croatia

University Hospital Zagreb

Zagreb, , Croatia

Faculty Hospital Brno

Brno, , Czechia

Neurological dept of Faculty

Hradec Králové, , Czechia

Fakultní nemocnice s poliklinikou Ostrava

Ostrava, , Czechia

Faculty Hospital Motol

Prague, , Czechia

Klinika Vseobecne

Prague, , Czechia

Nemocnice Teplice

Teplice, , Czechia

East Tallinn Central Hospital

Tallinn, , Estonia

West Tallinn Central Hospital

Tallinn, , Estonia

HUS Hyvinkaa Central Hospital

Hyvinkää, , Finland

OYKS Neurologian Klinikka

Oulu, , Finland

Neurologian Klinikka Seinajoen Keskussairaala

Seinäjoki, , Finland

Tampere University Hospital

Tampere, , Finland

Turun Yliopistollinen Keskussairaala Rakennus 3 1

Turku, , Finland

CHU de Lille

Lille, , France

CHU de Nantes

Nantes, , France

American Memorial Hospital

Reims, , France

David Tatishvili Medical Center

Tbilisi, , Georgia

Medical Center Health

Tbilisi, , Georgia

S. Khechinashvili Tbilisi State Medical University

Tbilisi, , Georgia

Universitaetsklinikum und Medizinische Fakultaet Heidelberg

Heidelberg, , Germany

Philipps-Universitaet Marburg

Marburg, , Germany

M S Ramaiah Medical College Hospital

Bangalore, Karnataka, India

St.John's Medical College and Hospital

Bangalore, Karnataka, India

Amrita Institute of Medical Sciences and Research

Kochi, Kerala, India

Kovai Medical Centre and Hospital

Coimbatore, , India

Sanjay Gandhi Post Graduate Institute of Medical Sciences

Lucknow, , India

Mallikatta Neuro and Research Centre

Mangalore, , India

Ospedale Regionale Torrette

Ancona, , Italy

Università de Bari

Bari, , Italy

Ospedale Binaghi Centro Sclerosi Multipla

Cagliari, , Italy

Azienda Ospedaliera Garibaldi

Catania, , Italy

Dipartimento di Neuroscienze

Catania, , Italy

Università G. D'Annunzio

Chieti, , Italy

Ospedale San Antonio Abate

Gallarate, , Italy

Universita degli Studi di Genova

Genova, , Italy

Ospedale e casa di riposo P. Richiedei

Gussago, , Italy

Ospedale San Raffaele

Milan, , Italy

Dipartimento di Scienze Neurologiche

Napoli, , Italy

Azienda Sanitaria Ospedaliera San Luigi Gonzaga

Orbassano, , Italy

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

Palermo, , Italy

Istituto Neurologico C. Mondino

Pavia, , Italy

Azienda Ospedaliera S. Camillo Forlanini

Roma, , Italy

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Roma, , Italy

Università di Roma La Sapienza

Roma, , Italy

American University of Beirut

Beirut, , Lebanon

Clinic of Neurology "Klinicki Centar"

Skopje, , North Macedonia

Helse Bergen HF Kvinneklinikken Haukeland Universitetssykehus Jonas

Bergen, , Norway

Regionsykehuset I Trondheim, Nevrologisk avd.

Trondheim, , Norway

10 Wojskowy Szpital Kliniczny

Bydgoszcz, , Poland

Wojewodzki Szpital Specjalistyczny im. M. Kopernika

Gdansk, , Poland

Niepubliczny Zespol Opieki Zdrowotnej

Krakow, , Poland

Medical Academy of Lodz

Lodz, , Poland

Panstwowy Szpital Kliniczny

Lublin, , Poland

Wojewodzki Szpital Specjalistyczny Oddział Neurologii z Pododdziałem Udarowym

Olsztyn, , Poland

Medical Academy

Poznan, , Poland

Medical Academy II

Warsaw, , Poland

Medical Academy

Warsaw, , Poland

Hospital Fernando da Fonseca

Amadora, , Portugal

Hospitais da Universidade de Coimbra

Coimbra, , Portugal

Hospital de Santa Maria

Lisbon, , Portugal

Centro Hospitalar de Coimbra

S. Martinho Do Bispo, , Portugal

"Dr. Carol Davilla" Military Clinical Hospital

Bucharest, , Romania

Centrul Medical SANA

Bucharest, , Romania

Spitalul Clinic Judetean Mures

Târgu Mureş, , Romania

County Hospital Timisoara

Timișoara, , Romania

Municipal Healthcare Institution "City Clinical Hospital #3"

Chelyabinsk, , Russia

State Healthcare Institution "Kaluga Regional Hospital"

Kaluga, , Russia

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

Kazan', , Russia

State Healthcare Institution "Kemerovo Regional Clinical Hospital"

Kemerovo, , Russia

State Medical Institution " Jursk Regional Clinical Hospital"

Kursk, , Russia

Moscow State Healthcare Institution City Clinical Hospital #11

Moscow, , Russia

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

Moscow, , Russia

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

Moscow, , Russia

Municipal Treatment Prophylactic Institution "City Hospital #33"

Nizhny Novgorod, , Russia

Federal State Institution " Siberian Reginal Medical Center of Roszdarv"

Novosibirsk, , Russia

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

Novosibirsk, , Russia

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

Rostov-on-Don, , Russia

State Healthcare Institution "Rostov Region Clinical Hospital"

Rostov-on-Don, , Russia

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

Saint Petersburg, , Russia

International Clinic and Hospital, Neurology

Saint Petersburg, , Russia

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

Saint Petersburg, , Russia

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

Saint Petersburg, , Russia

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"

Samara, , Russia

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

Saratov, , Russia

Regional State Healthcare Institution "State Smolensk Region Clinical Hospital"

Smolensk, , Russia

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

Tomsk, , Russia

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

Tyumen, , Russia

Vladimir Regional State Healthcare Institution "Regional Clinical Hospital"

Vladimir, , Russia

Municipal Healthcare Institution "Yaroslavi Clinical Hospital #8"

Yaroslavl, , Russia

State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1"

Yekaterinburg, , Russia

Clinical Centre of Serbia

Belgrade, , Serbia

Hospital for Prevention and Treatment of Cerebro-Vascular Diseases

Belgrade, , Serbia

Clinical Centre Niš

Niš, , Serbia

National Neuroscience Institute (TTSH Campus)

Singapore, , Singapore

National Cancer Center, Department of Neurology,

Gyeonggi-do, , South Korea

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

Seoul, , South Korea

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

Seoul, , South Korea

Seoul National University Hospital, Department of Neurology

Seoul, , South Korea

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

Seoul, , South Korea

Hospital Reina Sofia Cordoba

Córdoba, , Spain

Hospital Universitario Nuestra Senora de la Candelaria

Santa Cruz de Tenerife, , Spain

Sahlgrenskasjukhuset

Gothenburg, , Sweden

Karolinska University Hospital

Stockholm, , Sweden

Umea University Hospital

Umeå, , Sweden

Taipei Veterans

Taipei, , Taiwan

Chang Gung Medical Foundation- Linkou Branch No5

Taoyuan District, , Taiwan

Srinagarind Hospital

Khon Kaen, , Thailand

Dokuz Eylul University

Izmir, , Turkey (Türkiye)

Ondokuz Mayis Universitesi

Samsun, , Turkey (Türkiye)

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

Kharkiv, , Ukraine

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

Kiev, , Ukraine

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

Vinnitsa, , Ukraine

Rashid Hospital

Dubai, , United Arab Emirates

Kings College London

London, , United Kingdom

Countries

United States; 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

References

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.

Reference Type: DERIVED

PMID: 35019731 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35003076 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32447743 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29051829 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24502830 (View on PubMed)

Related Links

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

Trial Awareness and Transparency website

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

US Medical Information website, Medical Resources

Other Identifiers

28821

Identifier Type: -

Identifier Source: org_study_id