Oral Cladribine in Early Multiple Sclerosis (MS)
Information source: EMD Serono
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Multiple Sclerosis
Intervention: Cladribine (Drug); Cladribine (Drug); Placebo (Drug); Rebif® new formulation (RNF) (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: EMD Serono Official(s) and/or principal investigator(s): Bettina Stubinski, MD, Study Director, Affiliation: Merck Serono S.A., Geneva
Summary
A randomized, double-blind, clinical trial to assess the safety and efficacy of two doses of
oral cladribine versus 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
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 subjects with first
clinical demyelinating event at high risk of converting to MS.
Clinical Details
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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS
Secondary outcome: 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 MSNumber 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 Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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
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
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, subjects 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 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
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Male or female between 18 and 55 years old, inclusive
- Weighed between 40 to 120 kilogram (kg), inclusive
- Subject 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
- Subject 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
- Subject has EDSS 0 - 5. 0 at Screening
- Subject 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
- Subject 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,
subjects should use a hormonal contraceptive or intrauterine device for the
duration of the trial)
- Male subjects 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
- Subject has to provide written informed consent voluntarily, including, for United
states of America (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
- Subject 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:
- Subject has a diagnosis of MS (per McDonald criteria, 2005)
- Subject has any other disease that could better explain the subject's signs and
symptoms
- Subject has complete transverse myelitis or bilateral optic neuritis
- Subject using or has used any other approved MS disease modifying drug (DMD)
- Subject has used any investigational drug or undergone an experimental procedure
within 12 weeks prior to Study day 1
- Subject 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.
- Subject 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
- Subject suffered from current autoimmune disease other than MS
- Subject 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 subject or could affect compliance with the
study protocol
- Subject 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
- Subject has a history of seizures not adequately controlled by medications
- Subject has a known allergy to cladribine, interferon-beta, the excipient(s) of the
study medications, or to gadolinium- diethylenetriamine penta-acetic acid (DTPA)
- Subject 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])
- Subject has a history of chronic or clinically significant hematological
abnormalities
- Subject 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).
- Subject has previously been screened in this study (signed an informed consent) and
then withdrawn
- Subject 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
- Subject has received experimental MS treatment
- Subject has a history of alcohol or drug abuse
- Subject has intolerance or any contraindication to both paracetamol (acetaminophen)
and ibuprofen
- Subject has inability to administer subcutaneous injections either by self or by
caregiver
- Subject 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)
- Subject has a positive stool hemoccult test at Screening
Locations and Contacts
Natonal Cancer Center, Department of Neurology,, Gyeonggi-do, Korea, Republic of
Department of Neurology, 50 Ilwon-dong, Gangnam-gu, Seoul, 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
Yonsei University Medical Center, Department of Neurology, Yonsei University Medical Center, Seoul, Korea, Republic of
American University of Beirut, Beirut, Lebanon
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
Moscow State Healthcare Institution City Clinical Hospital #11, Moscow, 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
Municipal Treatment Prophylactic Institution "City Hospital #33", Nizhny Novgorod, Russian Federation
Federal State Institution " Siberian Reginal Medical Center of Roszdarv", Novosibirsk, Russian Federation
State Educational Institute of Higher Professional Education "Rostov State Medical University of Roszdrav", Rostov-on-Don, Russian Federation
State Healthcare Institution "Rostov Region Clinical Hospital", 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, Russian Federation
King Abdullah International Medical Research Center, King Saud Ben Abdulazziz University for Health Sciences, and National Guard Health Affairs, Riyadh, Saudi Arabia
Northern Neuroscience Center, Faculty of Medicine Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand
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, Ukraine
Research Site, Rockland, Massachusetts, United States
Additional Information
Starting date: December 2008
Last updated: August 2, 2013
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