RITUXIMAB for Anti-myelin-associated glycoprotein (anti-MAG) neuropathy

Inclusion criteria

• {"criterion_text":"-Age over 18\n-Women of childbearing potential must agree to use contraception for 365 days following administration of rituximab\n-Disease duration of 5 years or less and documented clinical worsening (clinical or ENMG or disability over the past 24 months)\n-IgM gammopathy, either MGUS or WM\n-Demyelinating polyneuropathy according to European Federation of Neurological Societies/Peripheral Nerve Society guidelines for chronic inflammatory demyelinating polyneuropathy on nerve conduction studies\n-Anti-MAG titre of 10 000 BTU or more\n-Total INCAT score of 1 point or more at baseline\n-Absence of immunoglobulin treatment within 3 months prior to inclusion\n-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\n-Negative β-HCG in women of childbearing potential"}

Exclusion criteria

• {"criterion_text":"-Unable to give informed consent\n-History or known presence of recurrent or chronic infection (e.g. viral hepatitis, HIV syphilis, tuberculosis)\n--\thistory of cancer/solid tumors less than 3 years old or not in remission, or history of hematological malignancies. Patients with a history of cancer with solid tumors cured or in remission for at least three years may be included. Patients with a history of basal cell carcinoma and squamous cell carcinoma in situ of the skin, carcinoma in situ of the cervix, which have been removed and resolved, with healthy margins documented on pathology, may be included.\n-History of alcohol (more than two drinks a day for a woman, more than 4 glasses a day for a man [WHO definition]) or other drug abuse within 6 months prior to randomization\n-History or currently active primary or secondary immunodeficiency\n-White blood cell count < 1500/mm3 or platelet count < 75 000/mm3\n-Angle closure glaucoma\n-Urinary retention related to urethroprostatic disorders\n-Uncontrolled psychotic disorders\n-Severe liver failure\n-Recent vaccination with live vaccines (<3months) and vaccination with live virus vaccines is not recommended during the overall study period\n-History of severe allergic or anaphylactic reaction to chimeric monoclonal antibody\n-Hypersensitivity known to one of the compounds of polaramide or methylprednisolone\n-Previous treatment with rituximab\n-Diseases known to cause polyneuropathy (e.g. Disease known to cause neuropathy: type 1 diabetes or type 2 diabetes that is unbalanced or has been in progress for more than 5 years;, uncontrolled thyroid disease, vitamin B1 or B12 deficiency, renal (GFR < 60ml ml/min/1,73 m2- MDRD formula) or liver disorder, myeloma, amyloidosis, cryoglobulinemia)\n-Indication of specific immunosuppressive therapy for WM\n-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\n-Congestive heart failure (NYHA III or IV)\n-Known active bacterial, viral, fungal mycobacterial infection"}

Primary endpoints

• {"endpoint_text":"-Clinical response defined as a 4 points (or more) increase of I-RODS between baseline and 12 months","definition_or_measurement_approach":"Clinical response defined as an increase of 4 points or more in the I-RODS score between baseline and 12 months"}

Secondary endpoints

• {"endpoint_text":"-INCAT disability score","definition_or_measurement_approach":"INCAT disability score assessed between baseline, 6 months and 12 months"}
• {"endpoint_text":"-6 minutes walk test","definition_or_measurement_approach":"Six-minute walk distance measured at specified visits"}
• {"endpoint_text":"-Timed 25 foot walk test","definition_or_measurement_approach":"Timed 25-foot walk measured at specified visits"}
• {"endpoint_text":"-9 hole peg test","definition_or_measurement_approach":"Nine-hole peg test performance measured at specified visits"}
• {"endpoint_text":"-ENMG motor sum score","definition_or_measurement_approach":"ENMG motor sum score assessed by electrophysiology"}
• {"endpoint_text":"-ENMG sensory sum score","definition_or_measurement_approach":"ENMG sensory sum score assessed by electrophysiology"}
• {"endpoint_text":"-MUNIX sum score","definition_or_measurement_approach":"MUNIX total score assessed at visits"}
• {"endpoint_text":"-Adverse events","definition_or_measurement_approach":"Safety assessed by recording adverse events"}
• {"endpoint_text":"-Anti-MAG titre","definition_or_measurement_approach":"Anti-MAG antibody titre measurement"}

France

Earliest CTIS Part Ii Submission Date

14-10-2024

Latest Decision Or Authorization Date

15-09-2025

Processing Time Days

336

Number Of Sites

17

Number Of Participants

90

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Saint Etienne

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France