Oral Cladribine in Early Multiple Sclerosis (MS)

NCT00725985 | Completed Phase 3 Results DMC

• 1 other identifier: 28821
• Study Type: interventional
• Target: 617
• Locations: 31 countries
• Sites: 152

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.

Conditions

Multiple Sclerosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  ITP: Baseline up to Week 96

Secondary Outcomes (48)

• ITP: Time to Develop Multiple Sclerosis (MS) Conversion According to the Revised McDonald Criteria (2005) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With McDonald MS

  ITP: Baseline up to Week 96

• ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan

  ITP: Baseline up to Week 96

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

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

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

  Time from Randomization up to 1217 days

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

  Time from Randomization up to 1217 days

Study Arms (12)

Cladribine 5.25 mg/kg (ITP)

EXPERIMENTAL

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.

Drug: Cladribine; Drug: Rebif® new formulation (RNF)

Cladribine 3.5 mg/kg (ITP)

EXPERIMENTAL

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.

Drug: Cladribine; Drug: Rebif® new formulation (RNF)

Placebo (ITP)

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Rebif® new formulation (RNF)

Cladribine 5.25 mg/kg, Rebif (OLMP)

EXPERIMENTAL

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.

Drug: Cladribine; Drug: Rebif® new formulation (RNF)

Cladribine 3.5 mg/kg, Rebif (OLMP)

EXPERIMENTAL

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.

Drug: Cladribine; Drug: Rebif® new formulation (RNF)

Placebo, Rebif (OLMP)

EXPERIMENTAL

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.

Drug: Placebo

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

EXPERIMENTAL

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.

Drug: Cladribine; Drug: Rebif® new formulation (RNF)

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

EXPERIMENTAL

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.

Drug: Cladribine; Drug: Rebif® new formulation (RNF)

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

EXPERIMENTAL

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.

Drug: Placebo

Cladribine 5.25 mg/kg, Rebif (LTFU)

EXPERIMENTAL

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.

Drug: Cladribine; Drug: Rebif® new formulation (RNF)

Cladribine 3.5 mg/kg, Rebif (LTFU)

EXPERIMENTAL

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.

Drug: Cladribine; Drug: Rebif® new formulation (RNF)

Placebo, Rebif (LTFU)

EXPERIMENTAL

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.

Drug: Placebo

Interventions

Cladribine DRUG

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

Cladribine 3.5 mg/kg (ITP); Cladribine 3.5 mg/kg, Rebif (LTFU); Cladribine 3.5 mg/kg, Rebif (OLMP); Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU); Cladribine 5.25 mg/kg (ITP); Cladribine 5.25 mg/kg, Rebif (LTFU); Cladribine 5.25 mg/kg, Rebif (OLMP); Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)

Placebo DRUG

Placebo matched to cladribine tablets were administered.

Placebo (ITP); Placebo, Rebif (LTFU); Placebo, Rebif (OLMP); Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)

Rebif® new formulation (RNF) 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 3.5 mg/kg, Rebif (LTFU); Cladribine 3.5 mg/kg, Rebif (OLMP); Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU); Cladribine 5.25 mg/kg (ITP); Cladribine 5.25 mg/kg, Rebif (LTFU); Cladribine 5.25 mg/kg, Rebif (OLMP); Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU); Placebo (ITP)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead

Study Sites (158)

Hope Research Institute Medical Plaza LLC Desert Hills

Phoenix, Arizona, United States

Location

Multiple Sclerosis Center Drive, Neurology Suite 701

Newport Beach, California, United States

Location

University of Colorado at Denver Health Sciences

Denver, Colorado, United States

Location

Fort Collins Neurology

Fort Collins, Colorado, United States

Location

MS Center of Brevard MIMA Centry Research Associates

Melbourne, Florida, United States

Location

University of South Florida

Tampa, Florida, United States

Location

MS Center of Atlanta

Atlanta, Georgia, United States

Location

Bruce Hughes West Building

Des Moines, Iowa, United States

Location

Michigan Neurology Associates

Clinton Township, Michigan, United States

Location

Henry Ford Hospital

Detroit, Michigan, United States

Location

University of Minnesota

Minneapolis, Minnesota, United States

Location

Dennis Dietrich

Great Falls, Montana, United States

Location

University of Medicine and Dentistry of New Jersey School of Neurology

Stratford, New Jersey, United States

Location

Upstate Clinical Research LLC 3

Albany, New York, United States

Location

Neurological Specialists of Long Island

Great Neck, New York, United States

Location

Multiple Sclerosis Center of Northeastern NY

New York, New York, United States

Location

Comprehensive MS Care Clinic at South Shore Multiple Sclerosis

Patchogue, New York, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, United States

Location

Meritcare Neuroscience Center Neurology

Fargo, North Dakota, United States

Location

University of Cincinnati

Cincinnati, Ohio, United States

Location

MS Center of Oklahoma

Oklahoma City, Oklahoma, United States

Location

Neurology and Sleep Medicine

Bethlehem, Pennsylvania, United States

Location

Swedish Medical Center Cherry Hill

Seattle, Washington, United States

Location

Neurology & Neurological Association of Tacoma

Tacoma, Washington, United States

Location

Instituto Medico Rodriguez Alfici

Godoy Cruz, Argentina

Location

Fundacion Rosarina de Neurorehabilitacion

Rosario, Argentina

Location

Krankenhaus der Barmherzigen Brüder

Linz, Austria

Location

Algemeen Ziekenhuis St Jan

Bruges, Belgium

Location

Cliniques Universitaires St-Luc

Brussels, Belgium

Location

Hopital Erasme

Brussels, Belgium

Location

CHU de Liege - Domaine Universitaire du Sart Tilman,

Liège, Belgium

Location

Clinical Center University of Sarajevo

Sarajevo, Bosnia and Herzegovina

Location

Military Medical Academy- Sofia (MMA)

Pleven, Bulgaria

Location

MBAL Rousse AD 1st

Rousse, Bulgaria

Location

Central Clinic Hospital

Sofia, Bulgaria

Location

Military Medical Academy

Sofia, Bulgaria

Location

National Heart Hospital

Sofia, Bulgaria

Location

Second MHAT

Sofia, Bulgaria

Location

Tokuda Hospital

Sofia, Bulgaria

Location

University Hospital St Naum

Sofia, Bulgaria

Location

Medical Centre Centromed 2000

Veliko Tarnovo, Bulgaria

Location

Ottawa General Hospital

Ottawa, Canada

Location

General Hospital Varazdin

Varaždin, Croatia

Location

University Hospital Zagreb

Zagreb, Croatia

Location

Faculty Hospital Brno

Brno, Czechia

Location

Neurological dept of Faculty

Hradec Králové, Czechia

Location

Fakultní nemocnice s poliklinikou Ostrava

Ostrava, Czechia

Location

Faculty Hospital Motol

Prague, Czechia

Location

Klinika Vseobecne

Prague, Czechia

Location

Nemocnice Teplice

Teplice, Czechia

Location

East Tallinn Central Hospital

Tallinn, Estonia

Location

West Tallinn Central Hospital

Tallinn, Estonia

Location

HUS Hyvinkaa Central Hospital

Hyvinkää, Finland

Location

OYKS Neurologian Klinikka

Oulu, Finland

Location

Neurologian Klinikka Seinajoen Keskussairaala

Seinäjoki, Finland

Location

Tampere University Hospital

Tampere, Finland

Location

Turun Yliopistollinen Keskussairaala Rakennus 3 1

Turku, Finland

Location

CHU de Lille

Lille, France

Location

CHU de Nantes

Nantes, France

Location

American Memorial Hospital

Reims, France

Location

David Tatishvili Medical Center

Tbilisi, Georgia

Location

Medical Center Health

Tbilisi, Georgia

Location

S. Khechinashvili Tbilisi State Medical University

Tbilisi, Georgia

Location

Universitaetsklinikum und Medizinische Fakultaet Heidelberg

Heidelberg, Germany

Location

Philipps-Universitaet Marburg

Marburg, Germany

Location

M S Ramaiah Medical College Hospital

Bangalore, Karnataka, India

Location

St.John's Medical College and Hospital

Bangalore, Karnataka, India

Location

Amrita Institute of Medical Sciences and Research

Kochi, Kerala, India

Location

Kovai Medical Centre and Hospital

Coimbatore, India

Location

Sanjay Gandhi Post Graduate Institute of Medical Sciences

Lucknow, India

Location

Mallikatta Neuro and Research Centre

Mangalore, India

Location

Ospedale Regionale Torrette

Ancona, Italy

Location

Università de Bari

Bari, Italy

Location

Ospedale Binaghi Centro Sclerosi Multipla

Cagliari, Italy

Location

Azienda Ospedaliera Garibaldi

Catania, Italy

Location

Dipartimento di Neuroscienze

Catania, Italy

Location

Università G. D'Annunzio

Chieti, Italy

Location

Ospedale San Antonio Abate

Gallarate, Italy

Location

Universita degli Studi di Genova

Genova, Italy

Location

Ospedale e casa di riposo P. Richiedei

Gussago, Italy

Location

Ospedale San Raffaele

Milan, Italy

Location

Dipartimento di Scienze Neurologiche

Napoli, Italy

Location

Azienda Sanitaria Ospedaliera San Luigi Gonzaga

Orbassano, Italy

Location

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

Palermo, Italy

Location

Istituto Neurologico C. Mondino

Pavia, Italy

Location

Azienda Ospedaliera S. Camillo Forlanini

Roma, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Roma, Italy

Location

Università di Roma La Sapienza

Roma, Italy

Location

American University of Beirut

Beirut, Lebanon

Location

Clinic of Neurology "Klinicki Centar"

Skopje, North Macedonia

Location

Helse Bergen HF Kvinneklinikken Haukeland Universitetssykehus Jonas

Bergen, Norway

Location

Regionsykehuset I Trondheim, Nevrologisk avd.

Trondheim, Norway

Location

10 Wojskowy Szpital Kliniczny

Bydgoszcz, Poland

Location

Wojewodzki Szpital Specjalistyczny im. M. Kopernika

Gdansk, Poland

Location

Niepubliczny Zespol Opieki Zdrowotnej

Krakow, Poland

Location

Medical Academy of Lodz

Lodz, Poland

Location

Panstwowy Szpital Kliniczny

Lublin, Poland

Location

Wojewodzki Szpital Specjalistyczny Oddział Neurologii z Pododdziałem Udarowym

Olsztyn, Poland

Location

Medical Academy

Poznan, Poland

Location

Medical Academy II

Warsaw, Poland

Location

Medical Academy

Warsaw, Poland

Location

Hospital Fernando da Fonseca

Amadora, Portugal

Location

Hospitais da Universidade de Coimbra

Coimbra, Portugal

Location

Hospital de Santa Maria

Lisbon, Portugal

Location

Centro Hospitalar de Coimbra

S. Martinho Do Bispo, Portugal

Location

"Dr. Carol Davilla" Military Clinical Hospital

Bucharest, Romania

Location

Centrul Medical SANA

Bucharest, Romania

Location

Spitalul Clinic Judetean Mures

Târgu Mureş, Romania

Location

County Hospital Timisoara

Timișoara, Romania

Location

Municipal Healthcare Institution "City Clinical Hospital #3"

Chelyabinsk, Russia

Location

State Healthcare Institution "Kaluga Regional Hospital"

Kaluga, Russia

Location

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

Kazan', Russia

Location

State Healthcare Institution "Kemerovo Regional Clinical Hospital"

Kemerovo, Russia

Location

State Medical Institution " Jursk Regional Clinical Hospital"

Kursk, Russia

Location

Moscow State Healthcare Institution City Clinical Hospital #11

Moscow, Russia

Location

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

Moscow, Russia

Location

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

Location

Municipal Treatment Prophylactic Institution "City Hospital #33"

Nizhny Novgorod, Russia

Location

Federal State Institution " Siberian Reginal Medical Center of Roszdarv"

Novosibirsk, Russia

Location

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

Novosibirsk, Russia

Location

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

Rostov-on-Don, Russia

Location

State Healthcare Institution "Rostov Region Clinical Hospital"

Rostov-on-Don, Russia

Location

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

Saint Petersburg, Russia

Location

International Clinic and Hospital, Neurology

Saint Petersburg, Russia

Location

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

Saint Petersburg, Russia

Location

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

Location

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

Location

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

Location

Regional State Healthcare Institution "State Smolensk Region Clinical Hospital"

Smolensk, Russia

Location

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

Tomsk, Russia

Location

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

Tyumen, Russia

Location

Vladimir Regional State Healthcare Institution "Regional Clinical Hospital"

Vladimir, Russia

Location

Municipal Healthcare Institution "Yaroslavi Clinical Hospital #8"

Yaroslavl, Russia

Location

State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1"

Yekaterinburg, Russia

Location

Clinical Centre of Serbia

Belgrade, Serbia

Location

Hospital for Prevention and Treatment of Cerebro-Vascular Diseases

Belgrade, Serbia

Location

Clinical Centre Niš

Niš, Serbia

Location

National Neuroscience Institute (TTSH Campus)

Singapore, Singapore

Location

National Cancer Center, Department of Neurology,

Gyeonggi-do, South Korea

Location

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

Seoul, South Korea

Location

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

Seoul, South Korea

Location

Seoul National University Hospital, Department of Neurology

Seoul, South Korea

Location

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

Seoul, South Korea

Location

Hospital Reina Sofia Cordoba

Córdoba, Spain

Location

Hospital Universitario Nuestra Senora de la Candelaria

Santa Cruz de Tenerife, Spain

Location

Sahlgrenskasjukhuset

Gothenburg, Sweden

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Umea University Hospital

Umeå, Sweden

Location

Taipei Veterans

Taipei, Taiwan

Location

Chang Gung Medical Foundation- Linkou Branch No5

Taoyuan District, Taiwan

Location

Srinagarind Hospital

Khon Kaen, Thailand

Location

Dokuz Eylul University

Izmir, Turkey (Türkiye)

Location

Ondokuz Mayis Universitesi

Samsun, Turkey (Türkiye)

Location

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

Kharkiv, Ukraine

Location

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

Kiev, Ukraine

Location

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

Location

Rashid Hospital

Dubai, United Arab Emirates

Location

Kings College London

London, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 35019731 DERIVED

• 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.

  PMID: 35003076 DERIVED

• 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.

  PMID: 32447743 DERIVED

• 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.

  PMID: 29051829 DERIVED

• 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.

  PMID: 24502830 DERIVED

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Cladribine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Bettina Stubinski, MD

  Merck Serono S.A., Geneva

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2008
• First Posted: July 31, 2008
• Study Start: December 31, 2008
• Primary Completion: July 31, 2011
• Study Completion: April 30, 2012
• Last Updated: March 22, 2021
• Results First Posted: October 10, 2013

Record last verified: 2021-02

Locations

BE (4); CR (2); KR (5); FR (3); TW (2); BU (9); IT (17); IN (6); CA (1); GB (1); SE (3); AE (1); NO (2); BO (1); RU (25); US (24); AR (2); AU (1); FI (5); PL (9); PT (4); TU (2); DE (2); CZ (6); ES (2); RO (4); GE (3); TH (1); UA (3); LE (1); SG (1)