Progressive Multiple SclerosisPhase 2ITT-PMSNCT01719159
Intrathecal Therapy With Monoclonal Antibodies in Progressive Multiple Sclerosis
A Phase 2 study testing Rituximab in people with Progressive Multiple Sclerosis, run by Anders Svenningsson at 2 sites in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Progressive Multiple Sclerosis
- What is being tested?
- Rituximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 2 sitesSweden
- Study dates
- Nov 2009to Jun 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
Sweden2 sites
Department of neurology, Umeå University Hospital
Umeå, 901 85
Dept of neurology, Uppsala University Hospital
Uppsala, SE-751 85
About this study
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.
Read the 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
- Being tested
- Rituximab
- Keywords
- Progressive multiple sclerosis, Monoclonal antibodies, Mabthera, Intrathecal treatment
- Medical subject headings
- Multiple Sclerosis, Chronic Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Mabthera
25 mg rituximab is injected intrathecally via an Ommaya reservoir once a week for 3 weeks. Patients are then followed for one year.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | Rituximab, 25 mg, is administrated intrathecal three times one week apart Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events
Feasibility of IT administered monoclonal antibodies
Measured: One year after completed treatment
Secondary outcomes (1)
Stabilisation of the neurological deterioration
Questionaires regarding MS quality of life, symptom inventory and fatigue will be used.
Measured: At 3,6,9,12 month after completed treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2012 (estimated)
- Study startNov 2009
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Progressive Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anders Svenningsson
- Sponsor type
- University, hospital or other
- Collaborators
- Västerbotten County Council, Sweden
- Responsible party
- Sponsor-investigator, Anders Svenningsson, Umeå University
- Investigators
- Anders Svenningsson, MD, PhD, Principal investigator, Umea university
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01719159
- Sponsor's protocol ID
- ITT-PMS
- Acronym
- ITT-PMS
- Status last verified
- Nov 2016
- First submitted
- 25 Oct 2012
- Last updated
- 22 Nov 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided: IPD will be shared upon request from the researcher or scientific journals
Publications
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.
PubMed 30305449Bergman 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.
PubMed 27536708
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intrathecal Therapy With Monoclonal Antibodies in Progressive Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT01719159
- Acronym / sponsor ID
- ITT-PMS / ITT-PMS
- Conditions
- Progressive Multiple Sclerosis
- Keywords
- Progressive multiple sclerosis, Monoclonal antibodies, Mabthera, Intrathecal treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Anders SvenningssonUniversity, hospital or other
- Collaborators
- Västerbotten County Council, Sweden
- Study start
- Nov 2009
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 1 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: RituximabRituximab, 25 mg, is administrated intrathecal three times one week apart |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: Mabthera25 mg rituximab is injected intrathecally via an Ommaya reservoir once a week for 3 weeks. Patients are then followed for one year. | Drug | Rituximab |
Primary outcome
Number of participants with adverse events
Time frame: One year after completed treatment
Feasibility of IT administered monoclonal antibodies
1 secondary outcome
Stabilisation of the neurological deterioration
Time frame: At 3,6,9,12 month after completed treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2016.
- Derived from this study: PubMed 30305449Bergman 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.
- Derived from this study: PubMed 27536708Bergman 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.
- Individual participant dataSharing planned: Undecided. IPD will be shared upon request from the researcher or scientific journals
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anders Svenningsson, MD, PhD principal investigator
Umea university
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab in people with Progressive Multiple Sclerosis, run by Anders Svenningsson at 2 sites in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events (time frame: One year after completed treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01719159, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2016.