Intrathecal Therapy With Monoclonal Antibodies in Progressive Multiple Sclerosis

NCT ID: NCT01719159

Last Updated: 2016-11-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2016-06-30

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

Conditions

Progressive Multiple Sclerosis

Keywords

Progressive multiple sclerosis; Monoclonal antibodies; Mabthera; Intrathecal treatment

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituximab

Rituximab, 25 mg, is administrated intrathecal three times one week apart

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

25 mg rituximab is injected intrathecally via an Ommaya reservoir once a week for 3 weeks. Patients are then followed for one year.

Interventions

Rituximab

25 mg rituximab is injected intrathecally via an Ommaya reservoir once a week for 3 weeks. Patients are then followed for one year.

Intervention Type: DRUG

Other Intervention Names

Mabthera

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Västerbotten County Council, Sweden

OTHER_GOV

Sponsor Role: collaborator

Anders Svenningsson

OTHER

Sponsor Role: lead

Responsible Party

Anders Svenningsson

MD, PhD, Assoc Prof

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Anders Svenningsson, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Umea university

Locations

Department of neurology, Umeå University Hospital

Umeå, , Sweden

Dept of neurology, Uppsala University Hospital

Uppsala, , Sweden

Countries

Sweden

References

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.

Reference Type: DERIVED

PMID: 30305449 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27536708 (View on PubMed)

Other Identifiers

ITT-PMS

Identifier Type: -

Identifier Source: org_study_id