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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 7 January 2013
Main ID:  EUCTR2008-003706-33-PT
Date of registration: 17/12/2008
Prospective Registration: Yes
Primary sponsor: Merck Serono SA - Geneva
Public title: A Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial of oral cladribine in subjects with a first clinical event at high risk of converting to MS - ORAl CLadribine in Early MS (ORACLE MS) Trial
Scientific title: A Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial of oral cladribine in subjects with a first clinical event at high risk of converting to MS - ORAl CLadribine in Early MS (ORACLE MS) Trial
Date of first enrolment: 06/03/2009
Target sample size: 600
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-003706-33
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no  
Phase: 
Countries of recruitment
Austria Belgium Bulgaria Czech Republic Estonia Finland France Germany
Greece Italy Norway Portugal Spain Sweden United Kingdom
Contacts
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Key inclusion & exclusion criteria
Inclusion criteria:
1. Be male or female between 18 and 55 years old, inclusive
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 initial 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
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 at Screening
6. Have no medical history or evidence of latent tuberculosis infection (LTBI) or active
tubercular disease (TB), as evidenced by the Mantoux TB skin test or a comparable sensitive test, according to local regulation guidelines if Mantoux test is not available and/or chest X-ray
7. ALL the hematological parameters must be normal at Screening according to the normal ranges provided by the centralized laboratory performing all the assessments
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. For the purpose of this trial, women of childbearing potential are defined as: "All female subjects after puberty unless they are post-menopausal for at least two years, are surgically sterile or are sexually inactive."
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
11. Voluntarily provide written informed consent, including, for USA, subject authorization under Health Insurance Portability and Accountability Act (HIPAA), 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
12. Must refuse any treatment already available for CIS such as Interferons and Glatiramer Acetate, entering the Initial Treatment Period of the Study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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
6. Subject who received oral or systemic corticosteroids or ACTH within 30 days prior to screening MRI. The MRI has to be performed 30 days after the oral or systemic corticosteroids or ACTH treatment. In case this interferes with MRI timing the screening period can be extended accordingly.
7. Subject has abnormal total bilirubin, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase greater thatn 2.5 x ULN
8. Subject suffers from current autoimmune disease other that MS
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 not adequately controlled by medications
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 SD1, 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)
23. Have a positive stool heme-occult test at Screening


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Subjects with a first clinical demyelinating event (Clinically Isolated Syndrome (CIS)) at high risk of converting to Multiple Sclerosis (MS)
MedDRA version: 14.0 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Intervention(s)

Product Name: Cladribine
Pharmaceutical Form: Tablet
INN or Proposed INN: CLADRIBINE
CAS Number: 4291638
Current Sponsor code: EMD280922
Other descriptive name: 2-chloro-2’-deoxy-ß-D-adenosine (2-CdA)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Rebif 44 micrograms solution for injection
Product Name: Interferon beta-1a FBS-free/HSA-free
Pharmaceutical Form: Solution for injection
INN or Proposed INN: INTERFERON BETA-1A
CAS Number: 9008-11-1
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 44-

Primary Outcome(s)
Main Objective: The primary objective of this study is to evaluate the effect of oral cladribine on the time to conversion to Clinical Definite Multiple Sclerosis (CDMS) according to the Poser criteria, defined by either a second attack or a sustained increase in EDSS score in subjects with a first clinical demyelinating event at high risk of converting to MS.
Primary end point(s): The single primary endpoint for the overall study is time to conversion to CDMS (from randomization), according to the Poser Criteria, defined by either a 2nd attack or a sustained increase in the EDSS score (EDSS=1 point if baseline was =1 and =4.5, or =1.5 points if baseline EDSS was 0, or =0.5 points if baseline was=5, over a period of at least three months).
Secondary Objective: Secondary objectives of Initial Treatment Period:
• The main secondary objective of this study, is to evaluate the effect of 2 dosage regimens of oral cladribine vs. placebo on the time to conversion to MS (from randomization) according to the revised McDonald criteria in subjects with a first clinical demyelinating event at high risk of converting to MS
• Evaluate the effect of oral cladribine on selected MRI parameters and disease
progression in subjects with a first clinical demyelinating event suggestive of MS
• Evaluate the effect of oral cladribine on Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test-Revised (BVMT-R) as measures of cognition in subjects with a first clinical demyelinating event suggestive of MS
• Evaluate the safety and tolerability of treatment with oral cladribine in subjects with a first clinical demyelinating event suggestive of MS.
Secondary Outcome(s)
Secondary ID(s)
2008-003706-33-CZ
28821
Source(s) of Monetary Support
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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