Intrathecal Therapy With Monoclonal Antibodies in Progressive Multiple Sclerosis

Study Overview
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Brief Summary
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This is a is a small scale open phase two interventional study to assess long-term stabilising effects of on neurological symptoms by regular intrathecal administered monoclonal antibodies in progressive multiple sclerosis.

Detailed Description
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There is presently no efficient therapy available in progressive MS, especially if there is no clear evidence of active inflammatory lesions or exacerbations as part of the disease. There are, however, evidence that some treatment protocols using cytotoxic drugs may to some extent slow down the progressive course. One specific feature of long-standing MS is that inflammatory cells accumulate in the central nervous system(CNS) compartment in the subarachnoid and perivascular spaces and may therefore be hard to reach via standard drug delivery through systemic administration. Administration of substances via the Intrathecal (IT) route, however, have shown to efficiently distribute in the subarachnoid spaces and may therefore be an attractive route of drug delivery

Official Title
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Intrathecal Therapy With Monoclonal Antibodies in Progressive Multiple Sclerosis

Conditions
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Progressive Multiple Sclerosis

Intervention / Treatment
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* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between the age of 18 and 65 years of age (nonfertile women or fertile women with effective contraceptive methods) Progressive MS since at least three years Some kind of documented progression of neurological symptoms during the previous two years. Expanded Disability Status Scale (EDSS) 4,0 - 7.0 (inclusive) (basically spared arm functions) Conventional therapy not indicated, contraindicated or failed Judged as compliant with the protocol Exclusion Criteria: Eligible for any of the conventional MS therapies Relapsing remitting multiple sclerosis (RRMS) Bleeding diathesis or medication contraindicating neurosurgical procedures or lumbar puncture Cognitive defect making informed consent unreliable Any medical condition contraindicating minor surgical procedures, as judged by anaesthesiologist Severe, uncontrolled heart disease Pregnant or lactating women Patients having contraindication for or otherwise not compliant with MRI investigations Documented vulnerability to infections Simultaneous treatment with other immunosuppressive drugs Documented allergy or intolerance to Rituximab Severe psychiatric condition

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab<br>Rituximab, 25 mg, is administrated intrathecal three times one week apart | Drug: Rituximab<br>* 25 mg rituximab is injected intrathecally via an Ommaya reservoir once a week for 3 weeks. Patients are then followed for one year.<br>* Other names: Mabthera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | Feasibility of IT administered monoclonal antibodies | One year after completed treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stabilisation of the neurological deterioration | Questionaires regarding MS quality of life, symptom inventory and fatigue will be used. | At 3,6,9,12 month after completed treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Progressive multiple sclerosis, Monoclonal antibodies, Mabthera, Intrathecal treatment