Clinical trial NCT01719159: Intrathecal Therapy With Monoclonal Antibodies in Progressive Multiple Sclerosis
Official title: Intrathecal Therapy With Monoclonal Antibodies in Progressive Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Progressive Multiple Sclerosis
Keywords: Progressive multiple sclerosis
Monoclonal antibodies
Mabthera
Intrathecal treatment
Lead sponsor: Umeå University
Sponsor class: OTHER
Collaborators: name: Västerbotten County Council, Sweden
First posted: 2012-11-01
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: One year after completed treatment
Secondary outcomes:
measure: Stabilisation of the neurological deterioration
timeFrame: At 3,6,9,12 month after completed treatment
Other outcomes:
measure: Immunological markers in blood
timeFrame: At 3,6,9,12 month after treatment
measure: Immunological markers in cerebrospinal fluid (CSF)
timeFrame: At 3, 6, 9 12 month after treatment
Locations:
city: Umeå
country: Sweden
facility: Department of neurology, Umeå University Hospital
city: Uppsala
country: Sweden
facility: Dept of neurology, Uppsala University Hospital
Study officials:
affiliation: Umea university
name: Anders Svenningsson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bergman J, Burman J, Gilthorpe JD, Zetterberg H, Jiltsova E, Bergenheim T, Svenningsson A. Intrathecal treatment trial of rituximab in progressive MS: An open-label phase 1b study. Neurology. 2018 Nov 13;91(20):e1893-e1901. doi: 10.1212/WNL.0000000000006500. Epub 2018 Oct 10.
citation: Bergman J, Dring A, Zetterberg H, Blennow K, Norgren N, Gilthorpe J, Bergenheim T, Svenningsson A. Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS. Neurol Neuroimmunol Neuroinflamm. 2016 Aug 2;3(5):e271. doi: 10.1212/NXI.0000000000000271. eCollection 2016 Oct.