Clinical trial NCT00725985: Oral Cladribine in Early Multiple Sclerosis (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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Keywords: Clinically Isolated Syndrome (CIS)
Early MS
Multiple Sclerosis
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
First posted: 2008-07-31
Enrollment: 617
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: ITP: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS
timeFrame: ITP: Baseline up to Week 96
Secondary outcomes:
measure: 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
timeFrame: ITP: Baseline up to Week 96
measure: 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
timeFrame: ITP: Baseline up to Week 96
measure: OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression
timeFrame: OLMP: Day 1, 90, 180, 270, 360, 450, 540, 630, 720 and 810
measure: LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Multiple Sclerosis (MS) According to the 2005 McDonald Criteria
timeFrame: Time from Randomization up to 1217 days
measure: LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria
timeFrame: Time from Randomization up to 1217 days
measure: LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria
timeFrame: Time from Randomization up to 1217 days
measure: ITP: Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) as Per Poser Criteria
timeFrame: ITP: Baseline up to week 96
measure: ITP: Percentage of Participants Converting to McDonald Multiple Sclerosis (MS) (2005)
timeFrame: ITP: Baseline up to week 96
measure: ITP: Number of New or Persisting Gd-enhanced Lesions
timeFrame: ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
measure: OLMP: Number of New or Persisting Gd-enhanced Lesions
timeFrame: OLMP: Baseline, Week 24, 48, 72 and 96
measure: LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions
timeFrame: LTFU: Baseline, Week 13, 24 and 36
measure: LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions
timeFrame: LTFU: Baseline, Week 13, 24, 36 and 48
measure: ITP: Number of New or Enlarging T2 Lesions
timeFrame: ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
measure: OLMP: Number of New or Enlarging T2 Lesions
timeFrame: OLMP: Baseline, Week 24, 48, 72 and 96
measure: LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions
timeFrame: LTFU: Baseline, Week 13, 24 and 36
measure: LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions
timeFrame: LTFU: Baseline, Week 13, 24, 36 and 48
measure: ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
timeFrame: ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
measure: OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
timeFrame: OLMP: Baseline, Week 24, 48, 72 and 96
measure: LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
timeFrame: LTFU: Baseline, Week 13, 24 and 36
measure: LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
timeFrame: LTFU: Baseline, Week 13, 24, 36 and 48
measure: ITP: Change From Baseline in Volume of T1 Gd-Enhanced Lesions
timeFrame: ITP: Baseline, Week 96
measure: OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
timeFrame: OLMP: Baseline, Week 24, 48, 72 and 96
measure: 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
timeFrame: LTFU: Baseline, Week 13, 24 and 36
measure: 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
timeFrame: LTFU: Baseline, Week 13, 24, 36 and 48
measure: ITP: Changes From Baseline in Volume of T2 Lesions
timeFrame: ITP: Baseline, Week 48 and 96
measure: OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions
timeFrame: OLMP: Baseline, Week 48 and 96
measure: LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T2 Lesions
timeFrame: LTFU: Baseline (Day 1)
measure: LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions
timeFrame: Baseline, Week 48
measure: ITP: Number of T1 Hypointense Lesions
timeFrame: ITP: Baseline, Week 48 and 96
measure: OLMP: Number of T1 Hypointense Lesions
timeFrame: OLMP: Baseline, Week 48 and 96
measure: LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of T1 Hypointense Lesions
timeFrame: LTFU: Baseline (Day 1)
measure: LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of T1 Hypointense Lesions
timeFrame: LTFU: Baseline, Week 48
measure: ITP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
timeFrame: ITP: Baseline up to Week 96
measure: OLMP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
timeFrame: OLMP: Baseline up to Week 96
measure: LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
timeFrame: LTFU: Baseline up to Week 48
measure: LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
timeFrame: Baseline up to Week 48
measure: ITP: Percentage of Participants With no New or Enlarging T2 Lesions
timeFrame: ITP: Baseline up to Week 96
measure: OLMP: Percentage of Participants With no New or Enlarging T2 Lesions
timeFrame: OLMP: Baseline up to 96
measure: LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions
timeFrame: Baseline up to Week 48
measure: LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions
timeFrame: LTFU: Baseline up to Week 48
measure: ITP: Percent Change From Baseline in Brain Volume
timeFrame: ITP: Baseline, Week 48 and 96
measure: OLMP: Percent Change From Baseline in Brain Volume
timeFrame: OLMP: Baseline, Week 48 and 96
measure: OLMP: Number of Relapses
timeFrame: Baseline up to Week 96
measure: LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Relapses
timeFrame: Baseline up to Week 48
measure: LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Relapses
timeFrame: Baseline up to Week 48
measure: OLMP: Annualized Relapse Rate
timeFrame: Baseline up to Week 96
measure: OLMP: Percentage of Relapse-Free Participants
timeFrame: Baseline up to Week 96
measure: ITP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: ITP: Baseline up to Week 96
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Hope Research Institute Medical Plaza LLC Desert Hills
state: Arizona
city: Newport Beach
country: United States
facility: Multiple Sclerosis Center Drive, Neurology Suite 701
state: California
city: Denver
country: United States
facility: University of Colorado at Denver Health Sciences
state: Colorado
city: Fort Collins
country: United States
facility: Fort Collins Neurology
state: Colorado
city: Melbourne
country: United States
facility: MS Center of Brevard MIMA Centry Research Associates
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: MS Center of Atlanta
state: Georgia
city: Des Moines
country: United States
facility: Bruce Hughes West Building
state: Iowa
city: Clinton Township
country: United States
facility: Michigan Neurology Associates
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Great Falls
country: United States
facility: Dennis Dietrich
state: Montana
city: Stratford
country: United States
facility: University of Medicine and Dentistry of New Jersey School of Neurology
state: New Jersey
city: Albany
country: United States
facility: Upstate Clinical Research LLC 3
state: New York
city: Great Neck
country: United States
facility: Neurological Specialists of Long Island
state: New York
city: New York
country: United States
facility: Multiple Sclerosis Center of Northeastern NY
state: New York
city: Patchogue
country: United States
facility: Comprehensive MS Care Clinic at South Shore Multiple Sclerosis
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Fargo
country: United States
facility: Meritcare Neuroscience Center Neurology
state: North Dakota
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Oklahoma City
country: United States
facility: MS Center of Oklahoma
state: Oklahoma
city: Bethlehem
country: United States
facility: Neurology and Sleep Medicine
state: Pennsylvania
city: Seattle
country: United States
facility: Swedish Medical Center Cherry Hill
state: Washington
city: Tacoma
country: United States
facility: Neurology & Neurological Association of Tacoma
state: Washington
city: Godoy Cruz
country: Argentina
facility: Instituto Medico Rodriguez Alfici
city: Rosario
country: Argentina
facility: Fundacion Rosarina de Neurorehabilitacion
city: Linz
country: Austria
facility: Krankenhaus der Barmherzigen Brüder
city: Brugge
country: Belgium
facility: Algemeen Ziekenhuis St Jan
city: Brussels
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Bruxelles
country: Belgium
facility: Hopital Erasme
city: Liège
country: Belgium
facility: CHU de Liege - Domaine Universitaire du Sart Tilman,
city: Sarajevo
country: Bosnia and Herzegovina
facility: Clinical Center University of Sarajevo
city: Pleven
country: Bulgaria
facility: Military Medical Academy- Sofia (MMA)
city: Rousse
country: Bulgaria
facility: MBAL Rousse AD 1st
city: Sofia
country: Bulgaria
facility: Central Clinic Hospital
city: Sofia
country: Bulgaria
facility: Military Medical Academy
city: Sofia
country: Bulgaria
facility: National Heart Hospital
city: Sofia
country: Bulgaria
facility: Second MHAT
city: Sofia
country: Bulgaria
facility: Tokuda Hospital
city: Sofia
country: Bulgaria
facility: University Hospital St Naum
city: Veliko Tarnovo
country: Bulgaria
facility: Medical Centre Centromed 2000
city: Ottawa
country: Canada
facility: Ottawa General Hospital
city: Varazdin
country: Croatia
facility: General Hospital Varazdin
city: Zagreb
country: Croatia
facility: University Hospital Zagreb
city: Brno
country: Czechia
facility: Faculty Hospital Brno
city: Hradec Kralove
country: Czechia
facility: Neurological dept of Faculty
city: Ostrava
country: Czechia
facility: Fakultní nemocnice s poliklinikou Ostrava
city: Prague
country: Czechia
facility: Faculty Hospital Motol
city: Prague
country: Czechia
facility: Klinika Vseobecne
city: Teplice
country: Czechia
facility: Nemocnice Teplice
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital
city: Tallinn
country: Estonia
facility: West Tallinn Central Hospital
city: Hyvinkaa
country: Finland
facility: HUS Hyvinkaa Central Hospital
city: Oulu
country: Finland
facility: OYKS Neurologian Klinikka
city: Seinajoki
country: Finland
facility: Neurologian Klinikka Seinajoen Keskussairaala
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turun Yliopistollinen Keskussairaala Rakennus 3 1
city: Lille Cedex
country: France
facility: CHU de Lille
city: Nantes
country: France
facility: CHU de Nantes
city: Reims Cedex
country: France
facility: American Memorial Hospital
city: Tbilisi
country: Georgia
facility: David Tatishvili Medical Center
city: Tbilisi
country: Georgia
facility: Medical Center Health
city: Tbilisi
country: Georgia
facility: S. Khechinashvili Tbilisi State Medical University
city: Heidelberg
country: Germany
facility: Universitaetsklinikum und Medizinische Fakultaet Heidelberg
city: Marburg
country: Germany
facility: Philipps-Universitaet Marburg
city: Bangalore
country: India
facility: M S Ramaiah Medical College Hospital
state: Karnataka
city: Bangalore
country: India
facility: St.John's Medical College and Hospital
state: Karnataka
city: Kochi
country: India
facility: Amrita Institute of Medical Sciences and Research
state: Kerala
city: Coimbatore
country: India
facility: Kovai Medical Centre and Hospital
city: Lucknow
country: India
facility: Sanjay Gandhi Post Graduate Institute of Medical Sciences
city: Mangalore
country: India
facility: Mallikatta Neuro and Research Centre
city: Ancona
country: Italy
facility: Ospedale Regionale Torrette
city: Bari
country: Italy
facility: Università de Bari
city: Cagliari
country: Italy
facility: Ospedale Binaghi Centro Sclerosi Multipla
city: Catania
country: Italy
facility: Azienda Ospedaliera Garibaldi
city: Catania
country: Italy
facility: Dipartimento di Neuroscienze
city: Chieti
country: Italy
facility: Università G. D'Annunzio
city: Gallarate
country: Italy
facility: Ospedale San Antonio Abate
city: Genova
country: Italy
facility: Universita degli Studi di Genova
city: Gussago
country: Italy
facility: Ospedale e casa di riposo P. Richiedei
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Napoli
country: Italy
facility: Dipartimento di Scienze Neurologiche
city: Orbassano
country: Italy
facility: Azienda Sanitaria Ospedaliera San Luigi Gonzaga
city: Palermo
country: Italy
facility: Villa Sofia Hospital Azienda Ospedaliera Villa Sofia P.zza Salerno e Resuttana 1
city: Pavia
country: Italy
facility: Istituto Neurologico C. Mondino
city: Roma
country: Italy
facility: Azienda Ospedaliera S. Camillo Forlanini
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Tor Vergata
city: Roma
country: Italy
facility: Università di Roma La Sapienza
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center, Department of Neurology,
city: Seoul
country: Korea, Republic of
facility: Department of Neurology, 50 Ilwon-dong, Gangnam-gu
city: Seoul
country: Korea, Republic of
facility: Department of Neurology, Asan Medical Center, 388-1 Pungnap 2-dong, Songpa-gu
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital, Department of Neurology
city: Seoul
country: Korea, Republic of
facility: Yonsei University Medical Center, Department of Neurology, Yonsei University Medical Center
city: Beirut
country: Lebanon
facility: American University of Beirut
city: Skopje
country: North Macedonia
facility: Clinic of Neurology "Klinicki Centar"
city: Bergen
country: Norway
facility: Helse Bergen HF Kvinneklinikken Haukeland Universitetssykehus Jonas
city: Trondheim
country: Norway
facility: Regionsykehuset I Trondheim, Nevrologisk avd.
city: Bydgoszcz
country: Poland
facility: 10 Wojskowy Szpital Kliniczny
city: Gdansk
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. M. Kopernika
city: Krakow
country: Poland
facility: Niepubliczny Zespol Opieki Zdrowotnej
city: Lodz
country: Poland
facility: Medical Academy of Lodz
city: Lublin
country: Poland
facility: Panstwowy Szpital Kliniczny
city: Olsztyn
country: Poland
facility: Wojewodzki Szpital Specjalistyczny Oddział Neurologii z Pododdziałem Udarowym
city: Poznan
country: Poland
facility: Medical Academy
city: Warsaw
country: Poland
facility: Medical Academy II
city: Warsaw
country: Poland
facility: Medical Academy
city: Amadora
country: Portugal
facility: Hospital Fernando da Fonseca
city: Coimbra
country: Portugal
facility: Hospitais da Universidade de Coimbra
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria
city: S. Martinho Do Bispo
country: Portugal
facility: Centro Hospitalar de Coimbra
city: Bucharest
country: Romania
facility: "Dr. Carol Davilla" Military Clinical Hospital
city: Bucharest
country: Romania
facility: Centrul Medical SANA
city: Targu-Mures
country: Romania
facility: Spitalul Clinic Judetean Mures
city: Timisoara
country: Romania
facility: County Hospital Timisoara
city: Chelyabinsk
country: Russian Federation
facility: Municipal Healthcare Institution "City Clinical Hospital #3"
city: Ekaterinburg
country: Russian Federation
facility: State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1"
city: Kaluga
country: Russian Federation
facility: State Healthcare Institution "Kaluga Regional Hospital"
city: Kazan
country: Russian Federation
facility: State Medical Institution "Republican Rehabilitation Clinic of Tatarstan Ministry of Health"
city: Kemerovo
country: Russian Federation
facility: State Healthcare Institution "Kemerovo Regional Clinical Hospital"
city: Kursk
country: Russian Federation
facility: State Medical Institution " Jursk Regional Clinical Hospital"
city: Moscow
country: Russian Federation
facility: Moscow State Healthcare Institution City Clinical Hospital #11
city: Moscow
country: Russian Federation
facility: Non-State Healthcare Institution "Central Clinical Hospital #2 named after N.A. Semasko of Russian Railways"
city: Moscow
country: Russian Federation
facility: 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: Nizhny Novgorod
country: Russian Federation
facility: Municipal Treatment Prophylactic Institution "City Hospital #33"
city: Novosibirsk
country: Russian Federation
facility: Federal State Institution " Siberian Reginal Medical Center of Roszdarv"
city: Novosibirsk
country: Russian Federation
facility: State institution Science Research Institute Clinical and Experimental Lymphology of Russian Academy of Medical Sciences
city: Rostov-on-Don
country: Russian Federation
facility: State Educational Institute of Higher Professional Education "Rostov State Medical University of Roszdrav"
city: Rostov-on-Don
country: Russian Federation
facility: State Healthcare Institution "Rostov Region Clinical Hospital"
city: Saint-Petersburg
country: Russian Federation
facility: 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: Samara
country: Russian Federation
facility: 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: Saratov
country: Russian Federation
facility: State Educational Institution of Higher Professional Education "Saratov State Medical University of Roszdrav" based on Clincial Hosptial #3 of Saratov State Medical University
city: Smolensk
country: Russian Federation
facility: Regional State Healthcare Institution "State Smolensk Region Clinical Hospital"
city: St Petersburg
country: Russian Federation
facility: Institute of Human Brain of Russian Academy of Science Dept. of Multiple Sclerosis
city: St Petersburg
country: Russian Federation
facility: International Clinic and Hospital, Neurology
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Healthcare Institution "Multifield City Hospital #2"
city: Tomsk
country: Russian Federation
facility: State Educational Institution of Higher Professional Education "Siberian State Medical University of Roszdrav"
city: Tyumen
country: Russian Federation
facility: Closed joint-stock society Medical sanitary unit "Nephtaynik" based the hospital
city: Vladimir
country: Russian Federation
facility: Vladimir Regional State Healthcare Institution "Regional Clinical Hospital"
city: Yaroslavl
country: Russian Federation
facility: Municipal Healthcare Institution "Yaroslavi Clinical Hospital #8"
city: Belgrade
country: Serbia
facility: Clinical Centre of Serbia
city: Belgrade
country: Serbia
facility: Hospital for Prevention and Treatment of Cerebro-Vascular Diseases
city: Niš
country: Serbia
facility: Clinical Centre Niš
city: Singapore
country: Singapore
facility: National Neuroscience Institute (TTSH Campus)
city: Cordoba
country: Spain
facility: Hospital Reina Sofia Cordoba
city: Sta. Cruz de Tenerife
country: Spain
facility: Hospital Universitario Nuestra Senora de la Candelaria
city: Goteborg
country: Sweden
facility: Sahlgrenskasjukhuset
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Umea
country: Sweden
facility: Umea University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation- Linkou Branch No5
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital
city: Izmir
country: Turkey
facility: Dokuz Eylul University
city: Samsun
country: Turkey
facility: Ondokuz Mayis Universitesi
city: Kharkiv
country: Ukraine
facility: State Established "Institute of Neurology, Psychiatry and Narcology of the AMS of Ukraine", Depart of Neurinfections and Multiple Sclorosis
city: Kiev
country: Ukraine
facility: Institue for Clinical Radiology of the State Establishment "Research Centre for Radiation Medicine of the AMS of Ukraino" Depart of Radiation Psychoneurology
city: Vinnitsa
country: Ukraine
facility: Vinnylsia Regional Psychoneurological Hosptial Named After O. I Yushchenko, Neurological Depart, Vinnytsia National Medical University Named After M. I. Pirogov, Chair of Neurology
city: Dubai
country: United Arab Emirates
facility: Rashid Hospital
city: London
country: United Kingdom
facility: Kings College London
Study officials:
affiliation: Merck Serono S.A., Geneva
name: Bettina Stubinski, MD
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
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.