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Oral Cladribine in Early Multiple Sclerosis (MS) (ORACLE MS)
This study is currently recruiting participants.
Verified by EMD Serono, December 2009
First Received: July 30, 2008   Last Updated: December 8, 2009   History of Changes
Sponsor: EMD Serono
Information provided by: EMD Serono
ClinicalTrials.gov Identifier: NCT00725985
  Purpose

A randomized, double-blind, clinical trial to assess the safety and efficacy of two doses of oral cladribine vs. placebo in subjects who had a first clinical demyelinating event (clinically isolated syndrome). Subjects 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 2 dosage regimens of oral cladribine vs. placebo on the time to conversion to Multiple Sclerosis (MS) (from randomization) according to the revised McDonald criteria in subjects with a first clinical demyelinating event at high risk of converting to MS.


Condition Intervention Phase
Multiple Sclerosis
Drug: Oral cladribine
Drug: Placebo
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • The single primary endpoint for the overall study, which will be determined during the Initial Treatment Period, is time to conversion to MS (from randomization), according to the revised McDonald criteria (2005). [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to conversion to clinically definite MS (from randomization), according to the Poser Criteria, defined by either a 2nd attack or a sustained increase (³1.5 points) in the EDSS score which will be determined during the initial treatment period. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 642
Study Start Date: October 2008
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Low-dose oral cladribine
Drug: Oral cladribine
Low-dose oral cladribine - 1.75 mg/kg/year. Dosed once/week for 4 weeks at the start of a cycle.
2: Experimental
High-dose oral cladribine
Drug: Oral cladribine
Low-dose oral cladribine - 3.5 mg/kg/year. Dosed once/week for 4 weeks at the start of a cycle.
3: Placebo Comparator
Placebo
Drug: Placebo
Placebo will be administered to subjects. The placebo looks exactly like the active treatment.

Detailed Description:

This will be a randomized, double blind, three-arm, placebo-controlled, multi-centre trial to evaluate the safety and efficacy of oral cladribine versus placebo in the treatment of subjects who have sustained a first clinical demyelinating event within 75 days prior to the Screening. Subjects must have a minimum of 2 clinically silent lesions on the Screening 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, subjects will then proceed from the Initial Treatment Period to either the Maintenance Treatment Period (with open-label interferon-beta treatment) or Long-Term Follow-up Treatment 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 Initial Treatment Period, is time to conversion to MS (from randomization), according to the revised McDonald criteria (2005).

For every subject, 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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Be male or female between 18 and 55 years old, inclusive (see Appendix C)
  2. Must weigh between 40-120 kg, inclusive
  3. 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, other than a paresthesia, vegetative or cerebral dysfunction
  4. Has at least two clinically silent lesions on the T2-weighted MRI scan, at screening, with a size of at least 3 mm, at least one of which is ovoid or periventricular or infratentorial on screening MRI
  5. Has EDSS 0 - 5.0 for at least one time point during the screening period before start of treatment with blinded study medication
  6. Have no medical history or evidence of latent tuberculosis infection (LTBI) or active tubercular disease (TB), as evidenced by TB skin test and/or chest X-ray
  7. The following hematological parameters must be normal (as defined below, inclusively) within 28 days of first dosing of blinded study medication at SD 1 (see also for further Hematological Testing and Entry Guidelines):

    • Hemoglobin = 11.6 - 16.2 G/DL
    • Leukocytes (total white blood cells [WBC]) = 4.1 - 12.3 x10E3/UL
    • Absolute lymphocytes = 1.02 - 3.36 x10E3/UL
    • Absolute neutrophil count (ANC) = 2.03 - 8.36 x10E3/UL
    • Platelet count = 140 - 450 x10E3/UL
  8. 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 (i.e. less than1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomized partner, or
    • be post-menopausal or surgically sterilized [Note: for Danish sites only, subjects should use a hormonal contraceptive or intra-uterine device for the duration of the trial]
  9. If male, he must be willing to use contraception to avoid contributing to pregnancies throughout the entire duration of the study and for 90 days following the last dose of study medication
  10. Be willing and able to comply with study procedures for the duration of the study Voluntarily provide written informed consent, including, for USA, subject authorization under Health Insurance Portability and Accountability Act (HIPAA) (see Appendix J), prior to any study-related procedure that is not part of normal medical care, and with the understanding that the subject may withdraw consent at any time without prejudice to their future medical care.

Exclusion Criteria:

  1. Subject has a diagnosis of multiple sclerosis (per McDonald criteria, 2005)
  2. Subject has any other disease that could better explain the subject's signs and symptoms
  3. Subject has complete transverse myelitis or bilateral optic neuritis
  4. Subject uses or has used any other approved MS disease modifying drug (DMD)
  5. Subject has used any investigational drug (other than Rebif® New Formulation) or undergone an experimental procedure within 12 weeks prior to SD1 with the exclusion of MS drug
  6. Subject received oral or systemic corticosteroids or ACTH within 30 days prior to SD1
  7. Subject has abnormal total bilirubin, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase
  8. Subject suffers from current autoimmune disease
  9. Subject suffers from psychiatric illness (including history of, or current, severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the study protocol
  10. Subject suffers from major medical illness such as cardiac (e.g. 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
  11. Subject has a history of seizures
  12. Subject has a known allergy to cladribine, IFN-beta, the excipient(s) of the study medications, or to gadolinium-DTPA
  13. Has any renal condition that would preclude the administration of gadolinium (e.g. acute or chronic severe renal insufficiency (GFR < 30 mL/min/1.73m2)
  14. Has a history of chronic or clinically significant hematological abnormalities
  15. History of active or chronic infectious disease or any disease that compromises immune function (e.g. HIV+, HTLV-1, Lyme disease, LTBI or TB, insulin-dependent diabetes).
  16. Subject has previously been screened in this study thus signed an informed consent and than withdrawn
  17. Subject has received any immunomodulatory or immunosuppressive therapy) at any time prior to Screening, 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 (e.g. natalizumab, alemtuzumab/Campath, anti-CD4), intravenous immunoglobuline G (IVIG), cytokines or anti-cytokine therapy
  18. Subject has received experimental MS treatment
  19. Subject has a history of alcohol or drug abuse
  20. Subject has intolerance or any contraindication to both paracetamol (acetaminophen) and ibuprofen
  21. Inability to administer subcutaneous injections either by self or by caregiver
  22. 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) Have a positive stool heme-occult test at Screening
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00725985

Contacts
Contact: Recruiting Sites in US - Local Medical Information 1-888-275-7376
Contact: Recruiting Sites Outside the US - Vissia Viglietta, MD 1-800-283-8088

Locations
United States, Massachusetts
Research Site Recruiting
Rockland, Massachusetts, United States
Contact: US Local Medical Information     888-275-7376        
Korea, Republic of
Department of Neurology, Asan Medical Center, 388-1 Pungnap 2-dong, Songpa-gu Recruiting
Seoul, Korea, Republic of
Contact     +822 3010 3444     kkkim@amc.seoul.kr    
Principal Investigator: Dr. Kwang-Kuk Kim            
Seoul National University Hospital, Department of Neurology Recruiting
Seoul, Korea, Republic of
Contact: Dr. Yoon-Ho Hong     +822 870 2474     yhh@snu.ac.kr    
Principal Investigator: Dr. Yoon-Ho Hong            
Department of Neurology, 50 Ilwon-dong, Gangnam-gu Recruiting
Seoul, Korea, Republic of
Contact: Dr. Kwang Ho Lee     +822 3410 3590     khlee3590@skku.edu    
Principal Investigator: Dr. Kwang Ho Lee            
Yonsei University Medical Center, Department of Neurology, Yonsei University Medical Center Recruiting
Seoul, Korea, Republic of
Contact     + 82 2 2228 1604     kimsm@yuhs.ac    
Principal Investigator: Seung Min Kim, MD            
Natonal Cancer Center, Department of Neurology, Recruiting
Gyeonggi-do, Korea, Republic of
Contact     + 82 31 920 2438     hojinkim@ncc.re.kr    
Principal Investigator: Dr. Ho Jin Kim            
Lebanon
American University of Beirut Recruiting
Beirut, Lebanon
Contact     +961-1-344-042     yamoutba@idm.net.lb    
Principal Investigator: Bassem Yamout, MD            
Russian Federation
Municipal Treatment Prophylactic Institution "City Hospital #33" Recruiting
Nizhny Novgorod, Russian Federation
Contact: Irina Sokolova     007 831 436 16 79     irsokol@inbox.ru    
Principal Investigator: Dr. Anna N. Belova            
Non-State Healthcare Institution "Central Clinical Hospital #2 named after N.A. Semasko of Russian Railways" Recruiting
Moscow, Russian Federation
Contact     007 (499) 160 50 19     ovvorobeva@mail.ru    
Principal Investigator: Dr. Olga V. Vorobeyva            
State Healthcare Institution "Kemerovo Regional Clinical Hospital" Recruiting
Kemerovo, Russian Federation
Contact: Vera Pavlova     +7 3842 39 64 22     vera.447_kem@mail.ru    
Principal Investigator: Dr. Nadejda A. Korotkevich            
State Medical Institution " Jursk Regional Clinical Hospital" Recruiting
Kursk, Russian Federation
Contact: Elena Logacheva     007 (4712) 35 49 86     lvb46@rambler.ru    
Principal Investigator: Dr. Vitaliy B. Loskov            
Federal State Institution " Siberian Reginal Medical Center of Roszdarv" Recruiting
Novosibirsk, Russian Federation
Contact: Nina Savchenko     700 383 228 72 61     ocrs@mail.ru    
Principal Investigator: Dr. Nadezhda A. Malkova            
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 Recruiting
Saint-Petersburg, Russian Federation
Contact: Alexey Popov     007 (812) 542 25 88     aepopow@yandex.ru    
Principal Investigator: Dr. Miroslav M. Odinak            
State Healthcare Institution "Kaluga Regional Hospital" Recruiting
Laluga, Russian Federation
Contact     007 4842 72 59 15     pasechnik@yandex.ru    
Principal Investigator: Dr. Elena S. Pasechnik            
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" Recruiting
Samara, Russian Federation
Contact: Nadezhda Kuznetsova     007 846 956 16 95     samaranevr@samtel.ru    
Principal Investigator: Dr. Irina P. Poverenova            
Closed joint-stock society Medical sanitary unit "Nephtaynik" based the hospital Recruiting
Tyumen, Russian Federation
Contact     007 (3452) 32 91 36     neurolog@bk.ru    
Principal Investigator: Dr. Stella A. Sivertseva            
State Medical Institution "Republican Rehabilitation Clinic of Tatarstan Ministry of Health" Recruiting
Kazan, Russian Federation
Contact: Timur Khaybullin     007 (843) 278 88 29     timuur@gmail.com    
Contact: A.            
Principal Investigator: Dr. Farit A. Khabirov            
State Educational Institution of Higher Professional Education "Saratov State Medical University of Roszdrav" based on Clincial Hosptial #3 of Saratov State Medical University Recruiting
Saratov, Russian Federation
Contact: Nikolay Makarov     007 845 252 56 62     nikola-makaro@vandex.ru    
Principal Investigator: Dr. Olga N. Voskresenskaya            
St. Petersburg State Healthcare Institution "Multifield City Hospital #2" Recruiting
St. Petersburg, Russian Federation
Contact     007 812 510 93 34     hospital_2_ND2@mail.ru    
Principal Investigator: Dr. Semen V. Perfiliev            
State Educational Institute of Higher Professional Education "I.M. Sechenov Moscow Medical Academy of Roszdrav" Russia based on A. Ya. Kozhevnikov Nervous Disease Clinic Recruiting
Moscow, Russian Federation
Contact: Tatiana Shmidt     007 499 248 65 38     tshmidt@complat.ru    
Principal Investigator: Dr. Nicolay N. Yakhno            
Municipal Healthcare Institution "City Clinical Hospital #3" Recruiting
Chelyabinsk, Russian Federation
Contact: Oksana Gavrikova     007 351 792 94 69     nervugmado@yandex.ru    
Principal Investigator: Dr. Galina N. Belskaya            
State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1" Recruiting
Ekaterinburg, Russian Federation
Contact: Elena Prazdnichkova     007 343 351 15 35     vli@okb1.ru    
Principal Investigator: Larisa I. Volkova            
State Educational Institution of Higher Professional Education "Siberian State Medical University of Roszdrav" Recruiting
Tomsk, Russian Federation
Contact: Marina Titova     007 3822 53 20 50     titovam82@tist.ru    
Principal Investigator: Dr. Valentina M. Alifirova            
Regional State Healthcare Institution "State Smolensk Region Clinical Hospital" Recruiting
Smolensk, Russian Federation
Contact: Anna Pysina     007 903 893 75 93     neuro_smolensk@mail.ru    
Principal Investigator: Dr. Natalia N. Maslova            
State Healthcare Institution "Rostov Region Clinical Hospital" Recruiting
Rostov-on-Don, Russian Federation
Contact: Vladimir Bulgakov     007 863 222 0346     gistrion@mail.ru    
Principal Investigator: Dr. Yuri V. Trinitatsky            
Municipal Healthcare Institution "Yaroslavi Clinical Hospital #8" Recruiting
Yaroslavi, Russian Federation
Contact     007 4852 44 53 44     neurol_08@mail.ru    
Principal Investigator: Dr. Nicolay N. Spirin            
Moscow State Healthcare Institution City Clinical Hospital #11 Recruiting
Moscow, Russian Federation
Contact: Serguey Shchur     007 (495) 543 57 04     nerv2005@mail.ru    
Principal Investigator: Dr. Alexey N. Boiko            
Vladimir Regional State Healthcare Institution "Regional Clinical Hospital" Recruiting
Vladimir, Russian Federation
Contact: Svetiana Kudryavtseva     007 4922 32 93 88     neurology@vtsnet.ru    
Principal Investigator: Dr. Anatoly A. Kudryavtsev            
State Educational Institute of Higher Professional Education "Rostov State Medical University of Roszdrav" Recruiting
Rostov-on-Don, Russian Federation
Contact: Zoya Goncharova     007 8632 63 56 05     centrms@mail.ru    
Principal Investigator: Dr. Victor A. Balyazin            
Saudi Arabia
King Abdullah International Medical Research Center, King Saud Ben Abdulazziz University for Health Sciences, and National Guard Health Affairs Recruiting
Riyadh, Saudi Arabia
Contact     +00966 - 252 0088 ext 16587     jumahm@ngha.med.sa    
Principal Investigator: Dr. Mohammed Al Jumah            
Thailand
Northern Neuroscience Center, Faculty of Medicine Maharaj Nakorn Chiang Mai Hospital Recruiting
Chiang Mai, Thailand
Contact     +66 53 946 757     siwaporn@mail.med.cmu.ac.th    
Principal Investigator: Assis. Prof. Siwaporn Chankrachang, MD            
Ukraine
Institue for Clinical Radiology of the State Establishment "Research Centre for Radiation Medicine of the AMS of Ukraino" Depart of Radiation Psychoneurology Recruiting
Kylv, Ukraine
Contact: Kateryna Antypohuk     +38 44 452 18 03     psycho@in.ua    
Principal Investigator: Prof. Konstantin Loganovsky            
Vinnylsia Regional Psychoneurological Hosptial Named After O. I Yushchenko, Neurological Depart, Vinnytsia National Medical University Named After M. I. Pirogov, Chair of Neurology Recruiting
Vinnytsia, Ukraine
Contact: Gennadiy Moskovko     +38 432 53 65 65     mosk6565@rambler.ru    
State Established "Institute of Neurology, Psychiatry and Narcology of the AMS of Ukraine", Depart of Neurinfections and Multiple Sclorosis Recruiting
Kharkiv, Ukraine
Contact: Vasilovskly Vitaliy     + 38 057 771 68 65     neuroinfection@kharkov.ukrtel.net    
Principal Investigator: Prof. Natalia Voloshyna            
Sponsors and Collaborators
EMD Serono
Investigators
Study Director: Vissia Viglietta, MD EMD Serono
  More Information

No publications provided

Responsible Party: EMD Serono ( George Hemsey, Sr. Clinical Project Mgr )
Study ID Numbers: 28821
Study First Received: July 30, 2008
Last Updated: December 8, 2009
ClinicalTrials.gov Identifier: NCT00725985     History of Changes
Health Authority: United States: Food and Drug Administration;   Algeria: Ministry of Health;   Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica;   Australia: Human Research Ethics Committee;   Austria: Agency for Health and Food Safety;   Belgium: Federal Agency for Medicinal Products and Health Products;   Bulgaria: Ministry of Health;   Canada: Health Canada;   Chile: Comisión Nacional de Investigación Científica y Tecnológica;   Croatia: Ministry of Health and Social Care;   Czech Republic: State Institute for Drug Control;   Estonia: The State Agency of Medicine;   Finland: Finnish Medicines Agency;   France: Ministry of Health;   Germany: Federal Institute for Drugs and Medical Devices;   Greece: National Organization of Medicines;   India: Ministry of Health;   Ireland: Ministry of Health;   Italy: National Institute of Health;   Korea: Food and Drug Administration;   Lebanon: Ministry of Public Health;   Lithuania: State Medicine Control Agency - Ministry of Health;   Macedonia: Ethics Committee;   Mexico: Ministry of Health;   Norway: Norwegian Medicines Agency;   Poland: Ministry of Health;   Portugal: National Pharmacy and Medicines Institute;   Romania: National Medicines Agency;   Serbia and Montenegro: Agency for Drugs and Medicinal Devices;   Singapore: Health Sciences Authority;   Spain: Ministry of Health;   Sweden: Medical Products Agency;   Switzerland: Federal Office of Public Health;   Taiwan: National Bureau of Controlled Drugs;   Thailand: Food and Drug Administration;   Turkey: Ministry of Health;   United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by EMD Serono:
Clinically Isolated Syndrome (CIS)
Early MS
Multiple Sclerosis

Additional relevant MeSH terms:
Cladribine
Autoimmune Diseases
Immunologic Factors
Demyelinating Diseases
Immune System Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Nervous System Diseases
Sclerosis
Immunosuppressive Agents
Pharmacologic Actions
Multiple Sclerosis
Pathologic Processes
Therapeutic Uses
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System

ClinicalTrials.gov processed this record on February 08, 2010