Anti-MAG neuropathy MedDRA version: 21.1 Level: LLT Classification code 10066137 Term: Anti-MAG neuropathy System Organ Class: 100000004852
Conditions
Interventions
Trade Name: Rituximab
Product Name: MabThera
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit: g gram(s)
Concentration type: equal
C
Sponsors
CHU SAINT-ETIENNE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age over 18 - Disease duration of 24 months or less and documented clinical worsening (clinical or ENMG or disability) over the past 12 months - IgM gammopathy, either MGUS or 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 ß-HCG in women of childbearing potential. 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 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: - Unable to give informed consent - History of severe allergic or anaphylactic reaction to chimeric monoclonal antibody - 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- 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 [(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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Demonstrate the efficacy of rituximab versus placebo in a subgroup of anti-MAG patients presumed as good clinical responders to improve neurological disability assessed by I-RODS score between baseline and 12 months.;Secondary Objective: 1- Evaluate the efficacy of rituximab versus placebo in a subgroup of anti-MAG patients presumed as good clinical responders to improve neurological disability assessed by I-RODS score between baseline and 6 months. 2- Evaluate the efficacy of rituximab versus placebo, between baseline, 6 months and 12 months, in a subgroup of anti-MAG patients presumed as good clinical responders to improve neurological disability assessed by: -Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, -Six minute walk test, -Timed 25-foot walk test, -9 hole peg test, -ENMG motor and sensory sum score -ENMG sensory sum score -MUNIX sum score 3- Evaluate the tolerability and short-term safety of rituximab between baseline and 12 months. 4- Explore the correlation between clinical response and change in anti-MAG antibody titre.;Primary end point(s): Demonstrate the efficacy of rituximab versus placebo in a subgroup of anti-MAG patients presumed as good clinical responders to improve neurological disability assessed by I-RODS score between baseline and 12 months. A patient will be considered with clinical response if an increase of I-RODS = 4 points within 12 months is observed. ;Timepoint(s) of evaluation of this end point: Months: 0, 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1- Evaluate the efficacy of rituximab versus placebo in a subgroup of anti-MAG patients presumed as good clinical responders to improve neurological disability assessed by I-RODS score between baseline and 6 months. 2- Evaluate the efficacy of rituximab versus placebo, between baseline, 6 months and 12 months, in a subgroup of anti-MAG patients presumed as good clinical responders to improve neurological disability assessed by: - Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, - Six minute walk test, - Timed 25-foot walk test, - 9 hole peg test, - ENMG motor and sensory sum score - ENMG sensory sum score - MUNIX sum score 3- Evaluate the tolerability and short-term safety of rituximab between baseline and 12 months. - Adverse events. 4- Explore the correlation between clinical response and change in anti-MAG antibody titre. - Anti-MAG titre. ;Timepoint(s) of evaluation of this end point: 1- Months: 0, 6 2- Months: 0, 6, 12 3- Months: 0, 12 4- Months: 12 | — |
Countries
France
Contacts
Public ContactProject manager
CHU SAINT-ETIENNE
Outcome results
None listed