Rituximab Therapy in Anti-Myelin Associated Glycoprotein Patients With Characteristics of Good Responders

NCT ID: NCT05136976

Last Updated: 2025-11-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-29

Study Completion Date

2028-12-31

Brief Summary

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Anti-MAG neuropathy is a progressively disabling orphan rare disorder due to a monoclonal immunoglobulin M(IgM) gammopathy displaying reactivity toward MAG, a glycoprotein of the peripheral nervous system. Its prevalence is around 1/100000 and to date, no treatment has proven efficacy in this disease, including rituximab in 2 Randomized Controlled Trails(RCTs).

Detailed Description

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However these trials have included unselected anti-MAG patients and methodological issues have been raised.

In COFRAMAG study, the largest cohort worldwide of anti-MAG patients, predictors of clinical response to rituximab were identified through analysis of 92 treated patients: shorter disease duration and anti-MAG titre above 10000 BTU. Thus this study will focus on rituximab efficacy in a subset of patients with disease duration of less than 2 years and anti-MAG titre above 10000 Buhlmann Titer Units (BTU). The investigators selected Inflammatory Rasch-built Overall Disability Scale (I-RODS) as primary outcome measure because its responsiveness was proven higher than INCAT/ Overall Neuropathy Limitation Score (ONLS) scales to detect clinical meaningful changes in newly treated patients with inflammatory neuropathies.

Conditions

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Anti-MAG Neuropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The THERAMAG study is a French academic multicentre, randomized, double-blind trial sponsored by the University Hospital of Saint-Etienne, comparing rituximab infusion to placebo infusion in anti-MAG patients presumed as good clinical responders.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
The randomization will be performed by the pharmacy. The treatment group will not be mentioned to the clinicians.

Study Groups

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Placebo

Patient with anti-MAG neuropathy will be included. They will randomized in placebo or Rituximab group.

They will have the same premedications prior to rituximab or placebo infusions:

* IV Dexchlorpheniramine Maleate IV: 10 mg
* IV Methylprednisolone: 40 mg
* PO Paracetamol : 1 gram

Group Type PLACEBO_COMPARATOR

Placebo infusion

Intervention Type DRUG

2 infusions of placebo at a 2 week interval.

Premedications

Intervention Type DRUG

Premedications prior to rituximab or placebo infusions:

* IV Dexchlorpheniramine Maleate IV: 10 mg
* IV Methylprednisolone: 40 mg
* PO Paracetamol : 1 gram

Rituximab

Patient with anti-MAG neuropathy will be included. They will randomized in placebo or Rituximab group.

They will have the same premedications prior to rituximab or placebo infusions:

* IV Dexchlorpheniramine Maleate IV: 10 mg
* IV Methylprednisolone: 40 mg
* PO Paracetamol : 1 gram

Group Type ACTIVE_COMPARATOR

Rituximab infusion

Intervention Type DRUG

2 infusions of 1 gram of rituximab at a 2 week interval (day 1 followed by day 15).

Premedications

Intervention Type DRUG

Premedications prior to rituximab or placebo infusions:

* IV Dexchlorpheniramine Maleate IV: 10 mg
* IV Methylprednisolone: 40 mg
* PO Paracetamol : 1 gram

Interventions

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Rituximab infusion

2 infusions of 1 gram of rituximab at a 2 week interval (day 1 followed by day 15).

Intervention Type DRUG

Placebo infusion

2 infusions of placebo at a 2 week interval.

Intervention Type DRUG

Premedications

Premedications prior to rituximab or placebo infusions:

* IV Dexchlorpheniramine Maleate IV: 10 mg
* IV Methylprednisolone: 40 mg
* PO Paracetamol : 1 gram

Intervention Type DRUG

Other Intervention Names

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Mabthera Sodium chloride (NaCl)

Eligibility Criteria

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Inclusion Criteria

* Disease duration of 5 years or less and documented clinical worsening (clinical or ENMG or disability) over the past 24 months
* IgM gammopathy, either MGUS or Waldenstrom Macroglobulinemia (WM)
* Demyelinating polyneuropathy according to European Federation of Neurological Societies/Peripheral Nerve Society guidelines for chronic inflammatory demyelinating polyneuropathy on nerve conduction studies.
* Anti-MAG titre of 10 000 BTU or more
* Total INCAT score of 1 point or more at baseline
* Absence of immunoglobulin treatment within 3 months prior to inclusion.
* Absence of immunosuppressive therapy within 6 months prior to inclusion, including steroid therapy of 2 months or more as part of the management of neuropathy.
* Negative β-human chorionic gonadotropin (HCG) in women of childbearing potential
* Women of childbearing potential must agree to use contraception for 365 days following administration of rituximab.

Exclusion Criteria

* \- Unable to give informed consent
* History of severe allergic or anaphylactic reaction to chimeric monoclonal antibody
* Hypersensitivity known to one of the compounds of polaramine or methylprednisolone
* Previous treatment with rituximab
* Diseases known to cause polyneuropathy (e.g. diabetes, uncontrolled thyroid disease, vitamin B1 or B12 deficiency, renal (GFR \< 60ml ml/min/1,73 m2- Modification of Diet in Renal Disease (MDRD) formula) or liver disorder, myeloma, amyloidosis, cryoglobulinemia)
* Indication of specific immunosuppressive therapy for WM
* Significant uncontrolled disease at baseline such as cardiovascular (including cardiac arrhythmia), pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine or gastrointestinal or any other significant disease that may prevent patient from participating in the study
* Congestive heart failure (NYHA III or IV)
* Known active bacterial, viral, fungal mycobacterial infection
* History or known presence of recurrent or chronic infection (e.g. viral hepatitis, HIV syphilis, tuberculosis).
* History of cancer, including solid tumors and haematological malignancies (except basal cell and in situ squamous carcinoma of the skin, in situ carcinoma of the cervix of the uterus that have been excised and resolved, with documented clear margins on pathology)
* History of alcohol (more than two drinks a day for a woman, more than 4 glasses a day for a man \[World Health Organization (WHO) definition\]) or other drug abuse within 6 months prior to randomization
* History or currently active primary or secondary immunodeficiency
* White blood cell count \< 1500/mm3 or platelet count \< 75 000/mm3
* Angle closure glaucoma,
* Urinary retention related to urethroprostatic disorders,
* Uncontrolled psychotic disorders,
* Severe liver failure,
* Recent vaccination with live vaccines (\<3months) and vaccination with live virus vaccines is not recommended during the overall study period.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ministry of Health, France

OTHER_GOV

Sponsor Role collaborator

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Anne-Laure KAMINSKY, MD

Role: PRINCIPAL_INVESTIGATOR

CHU de Saint-Etienne

Locations

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CHU Brest - La cavale blanche

Brest, , France

Site Status RECRUITING

CHU Grenoble - La tronche

Grenoble, , France

Site Status RECRUITING

CHU Lille - Roger Salengro

Lille, , France

Site Status RECRUITING

CHU Limoges - Dupuytren

Limoges, , France

Site Status RECRUITING

HCL lyon

Lyon, , France

Site Status RECRUITING

CHU La Timone - APHM

Marseille, , France

Site Status RECRUITING

CHU Nancy- Hôpital central

Nancy, , France

Site Status RECRUITING

Hôtel-Dieu et Hôpital GR Laënnec - CHU Nantes

Nantes, , France

Site Status RECRUITING

CHU Nice - Pasteur

Nice, , France

Site Status RECRUITING

APHP Pitié Salpêtrière

Paris, , France

Site Status RECRUITING

APHP - Kremlin-Bicêtre

Paris, , France

Site Status RECRUITING

CHU de Saint-Etienne

Saint-Etienne, , France

Site Status RECRUITING

CHU Strasbourg - Hautepierre

Strasbourg, , France

Site Status RECRUITING

CHU Toulouse - Pierre-Paul Riquet

Toulouse, , France

Site Status RECRUITING

CHU Tours - Bretonneau

Tours, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Anne-Laure KAMINSKY, MD

Role: CONTACT

(0)4 77 82 95 10 ext. +33

Carine LABRUYERE, CRA

Role: CONTACT

(0)4 77 12 04 69 ext. +33

Facility Contacts

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Yann Dr PEREON

Role: primary

+33 240 083 704

Other Identifiers

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2021-000009-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

19PH226

Identifier Type: -

Identifier Source: org_study_id

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