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Intrathecal Therapy With Monoclonal Antibodies in Progressive Multiple Sclerosis (ITT-PMS)

Primary Purpose

Progressive Multiple Sclerosis

Status
Completed
Phase
Phase 2
Locations
Sweden
Study Type
Interventional
Intervention
Rituximab
Sponsored by
Anders Svenningsson
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Progressive Multiple Sclerosis focused on measuring Progressive multiple sclerosis, Monoclonal antibodies, Mabthera, Intrathecal treatment

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of neurology, Umeå University Hospital
  • Dept of neurology, Uppsala University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Rituximab

Arm Description

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

Outcomes

Primary Outcome Measures

Number of participants with adverse events
Feasibility of IT administered monoclonal antibodies

Secondary Outcome Measures

Stabilisation of the neurological deterioration
Questionaires regarding MS quality of life, symptom inventory and fatigue will be used.

Full Information

First Posted
October 25, 2012
Last Updated
November 18, 2016
Sponsor
Anders Svenningsson
Collaborators
Västerbotten County Council, Sweden
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1. Study Identification

Unique Protocol Identification Number
NCT01719159
Brief Title
Intrathecal Therapy With Monoclonal Antibodies in Progressive Multiple Sclerosis
Acronym
ITT-PMS
Official Title
Intrathecal Therapy With Monoclonal Antibodies in Progressive Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
November 2009 (undefined)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Anders Svenningsson
Collaborators
Västerbotten County Council, Sweden

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Progressive Multiple Sclerosis
Keywords
Progressive multiple sclerosis, Monoclonal antibodies, Mabthera, Intrathecal treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rituximab
Arm Type
Experimental
Arm Description
Rituximab, 25 mg, is administrated intrathecal three times one week apart
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Mabthera
Intervention Description
25 mg rituximab is injected intrathecally via an Ommaya reservoir once a week for 3 weeks. Patients are then followed for one year.
Primary Outcome Measure Information:
Title
Number of participants with adverse events
Description
Feasibility of IT administered monoclonal antibodies
Time Frame
One year after completed treatment
Secondary Outcome Measure Information:
Title
Stabilisation of the neurological deterioration
Description
Questionaires regarding MS quality of life, symptom inventory and fatigue will be used.
Time Frame
At 3,6,9,12 month after completed treatment
Other Pre-specified Outcome Measures:
Title
Immunological markers in blood
Description
I.e. absolute numbers of major lymphocyte subset as well as regulatory cell subset
Time Frame
At 3,6,9,12 month after treatment
Title
Immunological markers in cerebrospinal fluid (CSF)
Description
I.e. absolute numbers of major lymphocyte subset as well as regulatory cell subset
Time Frame
At 3, 6, 9 12 month after treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anders Svenningsson, MD, PhD
Organizational Affiliation
Umea university
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of neurology, Umeå University Hospital
City
Umeå
ZIP/Postal Code
901 85
Country
Sweden
Facility Name
Dept of neurology, Uppsala University Hospital
City
Uppsala
ZIP/Postal Code
SE-751 85
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
IPD will be shared upon request from the researcher or scientific journals
Citations:
PubMed Identifier
30305449
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.
Results Reference
derived
PubMed Identifier
27536708
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.
Results Reference
derived

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Intrathecal Therapy With Monoclonal Antibodies in Progressive Multiple Sclerosis

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