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| Oral Cladribine in Early Multiple Sclerosis (MS) |
| Link to the ClinicalTrials.gov record | Information obtained from ClinicalTrials.gov on February 14, 2012 |
| Title of trial/grant title | Oral Cladribine in Early Multiple Sclerosis (MS) |
| Current status of trial | Active, not recruiting |
| Sponsors and collaborators | 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 Poser criteria in subjects with a first clinical demyelinating event at high risk of converting to MS. |
| Condition(s) | Multiple Sclerosis |
| Intervention(s) | Drug: Oral cladribine Drug: Oral cladribine Drug: Placebo |
| Phase | Phase III |
| Study type and design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment |
| 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 |
| Further study details | 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 Poser criteria. 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. |
| Primary outcome | 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. 2 years Yes |
| Secondary outcome | 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). 2 years Yes |
| Study start | October 2008 |
| Minimum age | 18 Years |
| Maximum age | 55 Years |
| Gender | Both |
| Eligibility 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. Hematological parameters must be normal (as defined by the central lab) 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 intrauterine 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 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 immunoglobulin 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 |
| Study chairs or principal investigators | Bettina Stubinski, MD, Study Director, Merck Serono S.A., Geneva, an affiliate of Merck KGaA, Darmstadt, Germany |
| Locations | Massachusetts, United States Research Site Rockland Massachusetts Korea, Republic of Natonal Cancer Center, Department of Neurology, Gyeonggi-do Korea, Republic of Department of Neurology, Asan Medical Center, 388-1 Pungnap 2-dong, Songpa-gu Seoul Korea, Republic of Seoul National University Hospital, Department of Neurology Seoul Korea, Republic of Department of Neurology, 50 Ilwon-dong, Gangnam-gu Seoul Korea, Republic of Yonsei University Medical Center, Department of Neurology, Yonsei University Medical Center Seoul Lebanon American University of Beirut Beirut Russian Federation Municipal Healthcare Institution "City Clinical Hospital #3" Chelyabinsk Russian Federation State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1" Ekaterinburg Russian Federation State Medical Institution "Republican Rehabilitation Clinic of Tatarstan Ministry of Health" Kazan Russian Federation State Healthcare Institution "Kemerovo Regional Clinical Hospital" Kemerovo Russian Federation State Medical Institution " Jursk Regional Clinical Hospital" Kursk Russian Federation State Healthcare Institution "Kaluga Regional Hospital" Laluga Russian Federation Non-State Healthcare Institution "Central Clinical Hospital #2 named after N.A. Semasko of Russian Railways" Moscow Russian Federation 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 Russian Federation Moscow State Healthcare Institution City Clinical Hospital #11 Moscow Russian Federation Municipal Treatment Prophylactic Institution "City Hospital #33" Nizhny Novgorod Russian Federation Federal State Institution " Siberian Reginal Medical Center of Roszdarv" Novosibirsk Russian Federation State Healthcare Institution "Rostov Region Clinical Hospital" Rostov-on-Don Russian Federation State Educational Institute of Higher Professional Education "Rostov State Medical University of Roszdrav" Rostov-on-Don Russian Federation 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 Russian Federation 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 Russian Federation State Educational Institution of Higher Professional Education "Saratov State Medical University of Roszdrav" based on Clincial Hosptial #3 of Saratov State Medical University Saratov Russian Federation Regional State Healthcare Institution "State Smolensk Region Clinical Hospital" Smolensk Russian Federation St. Petersburg State Healthcare Institution "Multifield City Hospital #2" St. Petersburg Russian Federation State Educational Institution of Higher Professional Education "Siberian State Medical University of Roszdrav" Tomsk Russian Federation Closed joint-stock society Medical sanitary unit "Nephtaynik" based the hospital Tyumen Russian Federation Vladimir Regional State Healthcare Institution "Regional Clinical Hospital" Vladimir Russian Federation Municipal Healthcare Institution "Yaroslavi Clinical Hospital #8" Yaroslavi Saudi Arabia King Abdullah International Medical Research Center, King Saud Ben Abdulazziz University for Health Sciences, and National Guard Health Affairs Riyadh Thailand Northern Neuroscience Center, Faculty of Medicine Maharaj Nakorn Chiang Mai Hospital Chiang Mai Ukraine 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 Kylv Ukraine Vinnylsia Regional Psychoneurological Hosptial Named After O. I Yushchenko, Neurological Depart, Vinnytsia National Medical University Named After M. I. Pirogov, Chair of Neurology Vinnytsia |
| Study ID numbers | 28821 |
| Last updated | September 28, 2011 |
| Record first received | July 30, 2008 |
| ClinicalTrials.gov identifier | NCT00725985 |
| Download date | Information obtained from ClinicalTrials.gov on February 14, 2012 |
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