NCT02545959

Brief Summary

The goal of investigators is to study the kinetics of action of a single dose of intrathecally-infused rituximab upon cerebro-spinal fluid (CSF) biological targets in progressive MS patients. Various markers of central nervous system inflammation (osteopontin, Tumor Necrosis Factor α, IgG secretion) and neurodegeneration (neurofilament) are studied at multiple time-points, assuming that a definitive action upon CSF biological targets would be strongly predictive of a delayed clinical action.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Nov 2015

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 7, 2015

Completed
3 days until next milestone

First Posted

Study publicly available on registry

September 10, 2015

Completed
3 months until next milestone

Study Start

First participant enrolled

November 30, 2015

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 22, 2019

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 2, 2019

Completed
Last Updated

October 3, 2019

Status Verified

April 1, 2019

Enrollment Period

3.2 years

First QC Date

September 7, 2015

Last Update Submit

October 2, 2019

Conditions

Multiple Sclerosis, Chronic ProgressiveNervous System Diseases

Keywords

Intrathecal Rituximabintrathecal chemotherapycerebrospinal fluidlumbar puncturePhysiological Effects of DrugsRituximab

Outcome Measures

Primary Outcomes (1)

  • Change in osteopontin level in CSF

    at day 4, day 21, day 180

Secondary Outcomes (3)

  • Change in Tumor Necrosis Factor alpha level in CSF

    day 4, day 21, day 180

  • Change in IgG synthesis in CSF

    day 4, day 21, day 180

  • Change in neurofilament level in CSF

    day 4, day 21, day 180

Other Outcomes (2)

  • Change in clinical parameters

    day 4, day 21, day 180, day 365

  • Brain volume atrophy

    day 180, day 365

Study Arms (3)

Control group

ACTIVE COMPARATOR

receive a single pulse of methylprednisolone IV (120mg)

Drug: methylprednisolone IV

Rituximab IT group

EXPERIMENTAL

receive a single intrathecal infusion of rituximab (with IV methylprednisolone 120mg to avoid side effect)

Drug: Rituximab ITDrug: methylprednisolone IV

Rituximab IT + IV group

EXPERIMENTAL

receive Rituximab IT as previous and Rituximab IV (375mg/m2) the same day

Drug: Rituximab ITDrug: methylprednisolone IVDrug: Rituximab IV

Interventions

Rituximab ITDRUG

CSF injection of intrathecal rituximab (20mg)

Also known as: intrathecal rituximab (Mabthera)
Rituximab IT + IV groupRituximab IT group
methylprednisolone IVDRUG

blood infusion of methylprednisolone IV (120mg)

Also known as: Solumedrol
Control groupRituximab IT + IV groupRituximab IT group
Rituximab IVDRUG

Blood infusion of rituximab (375mg/m2)

Also known as: Mabthera
Rituximab IT + IV group

Eligibility Criteria

Age45 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥45 years, male or female ;
  • Secondary or primary progressive MS, in progressive phase since \>2 years ;
  • EDSS ≥6.0 ;
  • Absence of alternative therapy.

You may not qualify if:

  • Relapsing-remitting phase of MS;
  • Contraindication to MRI, lumbar puncture, Trendelenburg position ;
  • Active infection or immunosuppressive state or treatment (actual or less than 6 months);
  • Earlier treatment with rituximab;
  • Dementia or severe psychiatric disorder.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Centre hospitalier F. Mitterrand (CH Pau)

Pau, 64000, France

Location

Related Publications (2)

  • Bonnan M, Ferrari S, Bertandeau E, Demasles S, Krim E, Miquel M, Barroso B. Intrathecal rituximab therapy in multiple sclerosis: review of evidence supporting the need for future trials. Curr Drug Targets. 2014;15(13):1205-14. doi: 10.2174/1389450115666141029234644.

    PMID: 25355180BACKGROUND

  • Bonnan M. Intrathecal immune reset in multiple sclerosis: exploring a new concept. Med Hypotheses. 2014 Mar;82(3):300-9. doi: 10.1016/j.mehy.2013.12.015. Epub 2013 Dec 31.

    PMID: 24417802BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis, Chronic ProgressiveNervous System Diseases

Interventions

RituximabMethylprednisolone Hemisuccinate

Condition Hierarchy (Ancestors)

Multiple SclerosisDemyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemDemyelinating DiseasesAutoimmune DiseasesImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsMethylprednisolonePrednisolonePregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Study Officials

  • Mickael Bonnan, MD

    CH Pau

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

September 7, 2015

First Posted

September 10, 2015

Study Start

November 30, 2015

Primary Completion

February 22, 2019

Study Completion

September 2, 2019

Last Updated

October 3, 2019

Record last verified: 2019-04

Locations

FR(1)