Study the action of a single dose of intrathecally-infused rituximab upon cerebro-spinal fluid (CSF) biological targets, assuming that a definitive action upon CSF biological targets would be strongly predictive of a delayed clinical action in patients with Progressive Multiple Sclerosis.

Intrathecal Rituximab in Progressive Multiple Sclerosis - EFFRITE

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2014-005493-11-FR

Enrollment

Registered

2018-03-15

Start date

2015-08-31

Completion date

Unknown

Last updated

2019-12-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Patients included in our study suffer from a progressive form of Multiple sclerosis and will be treated by intravenous and intrathecal rituximab, with intravenous methylprednisolone.

Interventions

Trade Name: Méthylprednisolone Mylan Product Name: méthylprednisolone Pharmaceutical Form: Powder for infusion Trade Name: Mabthera Pro

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Age =45 years, male or female ; Secondary or primary progressive MS, in progressive phase since >2 years ; EDSS =6.0 ; Absence of alternative therapy. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: 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); Severe heart failure or uncontrolled severe heart disease. Earlier treatment with rituximab; Dementia or severe psychiatric disorder.

Design outcomes

Primary

Measure	Time frame
Main Objective: Our goal is to study the kinetics of action of a single dose of intrathecally-infused rituximab upon cerebro-spinal fluid (CSF) biological targets. The main objective of the trial is to study the osteopontin level in CSF at d4 after a single intrathecal infusion of rituximab. CSF level is expected to normalize. ; Secondary Objective: The secondary objectives of the trial are : Biological outcomes in CSF (IgG synthesis, TNFa, neurofilament) at d4; delay to regain pre-therapeutic levels of biological targets in CSF (d21, d180) ; clinical data (walking time, nine hole peg test, EDSS, SDMT, fatigue intensity scale) at each time point, and brain MRI volumetry at d180 and d365. ; Primary end point(s): Primary end point: Osteopontine level in CSF at day 4. Osteopontine is a key cytokine participating to the polarization of Th1 and Th17 lymphocytes. Since CSF level is always high during MS, it is commonly used a criteria in recent studies. A decrease of CSF level would be indicative of an action upon T-cells. Our treatment will not only deplete CSF B-cells but this will impede the B/T-cell interaction necessary to T-cell activation. Therefore, this criteria is pertinent since it would demonstrate that targeting B cells will also affect T cell immunity in CSF. CSF osteopontine level is normally <0,4 µg/mL whereas levels are 1-30µg/mL in MS patients, well in range of commercial tests. A complete response is defined as a CSF level normalization. ; Timepoint(s) of evaluation of this end point: CSF will be drawn at day 4. Our treatment will immediately deplete CSF B-cells but a repopulation will probably occur in unknown delay. CSF is renewed 5-fold a day and intrathecally injected drugs are completely eliminated by day 2.	—

Measure

Time frame

Main Objective: Our goal is to study the kinetics of action of a single dose of intrathecally-infused rituximab upon cerebro-spinal fluid (CSF) biological targets. The main objective of the trial is to study the osteopontin level in CSF at d4 after a single intrathecal infusion of rituximab. CSF level is expected to normalize. ; Secondary Objective: The secondary objectives of the trial are : Biological outcomes in CSF (IgG synthesis, TNFa, neurofilament) at d4; delay to regain pre-therapeutic levels of biological targets in CSF (d21, d180) ; clinical data (walking time, nine hole peg test, EDSS, SDMT, fatigue intensity scale) at each time point, and brain MRI volumetry at d180 and d365. ; Primary end point(s): Primary end point: Osteopontine level in CSF at day 4. Osteopontine is a key cytokine participating to the polarization of Th1 and Th17 lymphocytes. Since CSF level is always high during MS, it is commonly used a criteria in recent studies. A decrease of CSF level would be indicative of an action upon T-cells. Our treatment will not only deplete CSF B-cells but this will impede the B/T-cell interaction necessary to T-cell activation. Therefore, this criteria is pertinent since it would demonstrate that targeting B cells will also affect T cell immunity in CSF. CSF osteopontine level is normally <0,4 µg/mL whereas levels are 1-30µg/mL in MS patients, well in range of commercial tests. A complete response is defined as a CSF level normalization. ; Timepoint(s) of evaluation of this end point: CSF will be drawn at day 4. Our treatment will immediately deplete CSF B-cells but a repopulation will probably occur in unknown delay. CSF is renewed 5-fold a day and intrathecally injected drugs are completely eliminated by day 2.

—

Secondary

Measure	Time frame
Secondary end point(s): Multiple secondary end points will be used: 1) intrathecal IgG synthesis at day 4. CSF IgG is commonly though to be synthesized by plasmablasts more than plasma cells. Although rituximab depletes only plasmablasts, and serum IgG are mostly unchanged after rituximab, our trial will examine CSF plasmablast depletion effectively impacts CSF IgG synthesis. 2) TNF alpha in CSF at day 4. TNF is secreted by lymphocytes and may play a major role in the development of cortical lesions. Although undetectable during RR-MS or basal state, TNF level is elevated during progressive phase of MS. A complete response would be the normalization of CSF level. 3) Neurofilament light (NFL) in CF at day 4. NFL is an axonal component release during neuronal destruction and level is elevated during MS. A normalization of CSF level would demonstrate a neuroprotective effect of our treatment. A complete response is defined as CSF level normalization. 4) Kinetics of inflammatory parameters relapse after initial improvement. Parameters are osteopontine, TNF, NFL levels in CSF and CSF IgG synthesis. CSF will be analyzed at day 21 and 180. 5) Clinical and MRI parameters at months 6 and 12. Clinical parameters are time walk 25 feet, nine hole peg test, EDSS, SDMT, fatigue scales (analogical, MFIS). MRI will monitor T2 lesion load, global, white and grey matter atrophy. ; Timepoint(s) of evaluation of this end point: IgG synthesis, TNF, NFL levels will be evaluated at day 4. Kinetics of relapse for inflammatory parameters will be examined at day 21 and 180. Clinical and MRI effects will monitored at months 6 and 12.	—

Measure

Time frame

Secondary end point(s): Multiple secondary end points will be used: 1) intrathecal IgG synthesis at day 4. CSF IgG is commonly though to be synthesized by plasmablasts more than plasma cells. Although rituximab depletes only plasmablasts, and serum IgG are mostly unchanged after rituximab, our trial will examine CSF plasmablast depletion effectively impacts CSF IgG synthesis. 2) TNF alpha in CSF at day 4. TNF is secreted by lymphocytes and may play a major role in the development of cortical lesions. Although undetectable during RR-MS or basal state, TNF level is elevated during progressive phase of MS. A complete response would be the normalization of CSF level. 3) Neurofilament light (NFL) in CF at day 4. NFL is an axonal component release during neuronal destruction and level is elevated during MS. A normalization of CSF level would demonstrate a neuroprotective effect of our treatment. A complete response is defined as CSF level normalization. 4) Kinetics of inflammatory parameters relapse after initial improvement. Parameters are osteopontine, TNF, NFL levels in CSF and CSF IgG synthesis. CSF will be analyzed at day 21 and 180. 5) Clinical and MRI parameters at months 6 and 12. Clinical parameters are time walk 25 feet, nine hole peg test, EDSS, SDMT, fatigue scales (analogical, MFIS). MRI will monitor T2 lesion load, global, white and grey matter atrophy. ; Timepoint(s) of evaluation of this end point: IgG synthesis, TNF, NFL levels will be evaluated at day 4. Kinetics of relapse for inflammatory parameters will be examined at day 21 and 180. Clinical and MRI effects will monitored at months 6 and 12.

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Countries

France

Contacts

Public ContactURC - Information sur Essai EFFRITE

Centre Hospitalier de Pau

stephane.debeugny@ch-pau.fr+33559726801

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 23, 2026