Status:
TERMINATED
Double Blind Combination of Rituximab by Intravenous and Intrathecal Injection Versus Placebo in Patients With Low-Inflammatory Secondary Progressive Multiple Sclerosis (RIVITaLISe)
Lead Sponsor:
National Institute of Neurological Disorders and Stroke (NINDS)
Conditions:
Multiple Sclerosis
Eligibility:
All Genders
18-65 years
Phase:
PHASE1
PHASE2
Brief Summary
Background: \- Secondary-progressive multiple sclerosis (SP-MS) is the chronic phase of multiple sclerosis (MS). The majority of people who have relapsing-remitting MS eventually develop SP-MS. There...
Detailed Description
Objective: The primary goal of this study is to define the safety and efficacy of combined systemic and intrathecal (IT) B cell-depleting therapy (i.e. anti-CD20, rituximab) in patients with secondary...
Eligibility Criteria
Inclusion
- INCLUSION CRITERIA:
- MS as defined by the modified McDonald s criteria (Polman, Reingold et al. 2005)
- SP-MS as documented by lack of MS relapse for the past 1 year and non-remitting/sustained (\> 3 months) progression of disability
- Age 18-65, inclusive, at the time of the first screening baseline visit
- EDSS 3.0 to 7.0, inclusive, at the time of the first screening baseline visit
- Able to provide informed consent
- Willing to participate in all aspects of trial design and follow-up
- Lack of CEL on all MRIs performed within the last 12 months or if patient has CEL, then documentation that they tried and failed or could not tolerate FDA approved disease modifying therapies (DMTh)
- Not receiving any DMTh (such as IFN-beta preparation, glatiramer acetate, corticosteroid, natalizumab, fingolimod, immunosuppressive agents or experimental therapeutics) for a period of at least 1 month before enrollment in the study, allowing for at least a 1-year
- period off therapy prior to the first study dose
- Agreeing to commit to the use of a reliable/accepted method of birth control (i.e. hormonal contraception (birth control pills, injected hormones, vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom with spermicide) or they have undergone surgical sterilization (such as hysterectomy, tubal ligation, or vasectomy)) during enrollment in the study and through 12 months after the last dose of study drug
- EXCLUSION CRITERIA:
- RR-MS or PP-MS
- Evidence of clearly documented MS relapse within the last 1 year
- Alternative diagnoses that can explain neurological disability and MRI findings
- Clinically significant medical disorders that, in the judgment of the investigators could cause CNS tissue damage, limit its repair, expose the patient to undue risk of harm or prevent the patient from completing the study (such as, but not limited to cerebrovascular disease, ischemic cardiomyopathy, clotting disorder, brittle diabetes, neurodegenerative disorder)
- Pregnant or breastfeeding female
- History or sign of congenital or acquired immunodeficiency or chronic infections, such as HIV/AIDS, Hepatitis A, B or C, HTLV-1 carrier and others that would expose patient to risks of pathogen reactivation associated with rituximab treatment
- Abnormal screening/baseline blood tests exceeding any of the limits defined below:
- Serum alanine transaminase or aspartate transaminase levels which are greater than three times the upper limit of normal values.
- Total white blood cell count \< 3 000/mm(3)
- Platelet count \< 85 000/mm(3)
- Serum creatinine level \> 2.0 mg/dl and eGFR (glomerular filtration rate) \< 60
- Serological evidence of HIV, HTLV-1 or active hepatitis A, B or C
- Positive pregnancy test
- Positive CSF or serum quantitative PCR for JC virus on CSF collected from the baseline spinal tap (test will be performed by CLIA certified laboratory of Gene Major, NINDS)
- Total serum IgG \< 600mg/dl (nl 642-1730mg/dl) or total serum IgM \< 30mg/dl (nl 34-342mg/dl) as these Ig deficiencies would suggest underlying abnormalities with B cell function/maturation
Exclusion
Key Trial Info
Start Date :
September 1 2010
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 1 2015
Estimated Enrollment :
44 Patients enrolled
Trial Details
Trial ID
NCT01212094
Start Date
September 1 2010
End Date
December 1 2015
Last Update
March 28 2016
Active Locations (1)
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1
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892