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

NCT05136976 | Recruiting Phase 3 DMC

• 2 other identifiers: 19PH2262021-000009-25
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 15

Brief Summary

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).

Conditions

Anti-MAG Neuropathy

Keywords

Neuropathy; Anti-MAG; Rituximab; I-RODS; placebo

Outcome Measures

Primary Outcomes (1)

• I-RODS score

  Clinical response defined as a 4 points (or more) change of I-RODS between baseline and 12 months. I-RODS is a 24-item patient-reported outcome measure which maximum score is 48. It is a linearly weighted scale that specifically captures activity and social participation limitations in patients with inflammatory neuropathies, including Monoclonal Gammopathy of Unknown Significance (MGUS) related polyneuropathies.

  Baseline and 12 months

Secondary Outcomes (9)

• Inflammatory Neuropathy Cause and Treatment (INCAT) disability score

  Months: 0, 6, 12

• Six minute walk test

  Months : 0, 6, 12

• Timed 25- foot walk (FW) test

  Months : 0, 6, 12

• 9 hole peg test

  Months : 0, 6, 12

• ElectroNeuroMyography (ENMG)

  Months : 0, 6, 12

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo infusion; Drug: Premedications

Rituximab

ACTIVE COMPARATOR

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

Drug: Rituximab infusion; Drug: Premedications

Interventions

Rituximab infusion DRUG

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

Also known as: Mabthera

Rituximab

Placebo infusion DRUG

2 infusions of placebo at a 2 week interval.

Also known as: Sodium chloride (NaCl)

Placebo

Premedications DRUG

Premedications prior to rituximab or placebo infusions: * IV Dexchlorpheniramine Maleate IV: 10 mg * IV Methylprednisolone: 40 mg * PO Paracetamol : 1 gram

Placebo; Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• \- 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,

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Ministry of Health, France: collaborator

Study Sites (15)

CHU Brest - La cavale blanche

Brest, 29200, France

RECRUITING

CHU Grenoble - La tronche

Grenoble, 38700, France

RECRUITING

CHU Lille - Roger Salengro

Lille, 59037, France

RECRUITING

CHU Limoges - Dupuytren

Limoges, 87170, France

RECRUITING

HCL lyon

Lyon, 69002, France

RECRUITING

CHU La Timone - APHM

Marseille, 13915, France

RECRUITING

CHU Nancy- Hôpital central

Nancy, 54035, France

RECRUITING

Hôtel-Dieu et Hôpital GR Laënnec - CHU Nantes

Nantes, France

RECRUITING

CHU Nice - Pasteur

Nice, 06031, France

RECRUITING

APHP Pitié Salpêtrière

Paris, 75651, France

RECRUITING

APHP - Kremlin-Bicêtre

Paris, 94270, France

RECRUITING

CHU de Saint-Etienne

Saint-Etienne, France

RECRUITING

CHU Strasbourg - Hautepierre

Strasbourg, 67091, France

RECRUITING

CHU Toulouse - Pierre-Paul Riquet

Toulouse, 31059, France

RECRUITING

CHU Tours - Bretonneau

Tours, 37044, France

RECRUITING

MeSH Terms

Interventions

Rituximab; Sodium Chloride; Premedication

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Drug Therapy; Therapeutics

Study Officials

• Anne-Laure KAMINSKY, MD

  CHU de Saint-Etienne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne-Laure KAMINSKY, MD

CONTACT

(0)4 77 82 95 10; a.laure.kaminsky@chu-st-etienne.fr

Carine LABRUYERE, CRA

CONTACT

(0)4 77 12 04 69; carine.labruyere@chu-st-etienne.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The randomization will be performed by the pharmacy. The treatment group will not be mentioned to the clinicians.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 16, 2021
• First Posted: November 30, 2021
• Study Start: June 29, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (15)