Chronic inflammatory demyelinating polyradiculoneuropathy MedDRA version: 20.0 Level: LLT Classification code 10072650 Term: CIDP System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: PT Classification code 10057645 Term: Chronic inflammatory demyelinating polyradiculoneuropathy System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: PT Classification code 10057645 Term: Chronic inflammatory demyelinating polyradiculoneuropathy System
Conditions
Interventions
Trade Name: MABTHERA - 1 FIALA 500 MG 50 ML
Product Name: Rituximab
Product Code: [Rituximab]
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 1747
Sponsors
IRCCS ISTITUTO CLINICO HUMANITAS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subject is = 18 years of age at Visit 1 (screening) - Subject has a documented diagnosis of definite or probable CIDP according to the EFNS/PNS criteria 2010 (Joint Task Force of the EFNS and the PNS, 2010) -. Subject has an Ig-dependency confirmed by clinical examination in the 12 months before screening and documented in medical history (ie, that a decrease or withdrawal of immunoglobulin was attempted that resulted in a clinically relevant decrease in function) - If the Ig dependency has been confirmed within 12 to 6 months before screening, the subject has to be on a stable dosage (not more than ±20% deviation) for SCIg or IVIg and a fixed interval for at least 3 months of either treatment, ie, once or twice weekly ±2 days for SCIg or every 2 to 8 weeks ±5 days for IVIg, respectively, for stability in functioning between dosing. If the Ig dependency has been confirmed within 6 months before Screening Visit, the stable dose and fixed interval is not required - Subject can take steroids at the maximum dosage equivalent to 12.5 mg/day of prednisone or 25 mg on alternate day or pulsed 400 mg/monthly of methylprednisolone as far as the dosage has been maintained stable (± 20%) in the previous 6 months. This treatment should be maintained unchanged during the sixmonth treatment period and the six-month follow-up period - Subject has adequate peripheral venous access - Female subjects of childbearing potential must have a negative serum pregnancy test and agree to use a highly effective method of birth control, during the study and for a period 12 months after their last dose of study drug - Male subject with a partner of childbearing potential must be willing to use an highly effective method of birth control when sexually active during the study and for 12 months after the final administration of rituximab/placebo. 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 36 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: - Subject has a current diagnosis or has a history of Type 1 or Type 2 diabetes mellitus - Subject with IgM paraproteinemia with anti-myelin associated glycoprotein antibodies - Subject has Multifocal Motor Neuropathy with conduction block (MMN) - Patient with a CIDP relapse or significant worsening of symptoms within 6 months of randomization - Clinical or known evidence of associated medical conditions that might cause neuropathy including but not limited to connective tissue disease, Lyme disease, cancer (with the exclusion of benign skin cancer), Castleman’s disease and systemic lupus erythematosus, malignant plasma cell dyscrasia, lymphoma, osteosclerotic myeloma, POEMS, or agents that may lead to neuropathy eg, amiodarone therapy - Female who is pregnant or lactating - Subjects has any medical condition (acute or chronic illness) or psychiatric condition that, in the opinion of the investigator, could harm the subject or would compromise the subject’s ability to participate in the study - Subject with congestive heart failure or a moderate or higher impairment of cardiac function - Subject has renal impairment defined as: serum creatinine > 1.4 mg/dL for females and 1.5 mg/dL for males - Subject has an absolute neutrophil count 1.5 × upper limit of the normal (ULN) range, unless in context of Gilbert’s syndrome; aspartate aminotransferase (AST), alanine aminotransferase (ALT) >3 × ULN range; alkaline phosphatase (AP) >1.5 × ULN range; gammaglutamyl-transferase (GGT) >3 × ULN range - Subject has a history of chronic alcohol or drug abuse within the previous 12 months -. Subject has a history of clinically relevant ongoing chronic infections including but not limited to human immunodeficiency virus (HIV), hepatitis B, hepatitis C, active or latent tuberculosis or is tested positive for HIV (anti-HIV1 or anti-HIV2 antibodies) hepatitis B (HBsAG positive or HBcAb positive without HBsAb) or hepatitis C (HCV antibodies) at the screening visit - Subject has severe immunocompromission or a family history of primary immunodeficiency - Subject has a clinical relevant active infection (eg. sepsis, pneumonia, and abscess) or has had a serious infection (resulting in hospitalization or parenteral antibiotic treatment) within 6 weeks prior to the first dose of rituximab/placebo - Subject has an active neoplastic disease or history of neoplastic disease within 5 years of study entry (except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix which has been definitely treated with standard of care approaches) - Subject was treated with plasma exchange or immunoabsorption within 3 months of randomization, with immunosuppressive/chemotherapeutic medications including azathioprine, cyclophosphamide, cyclosporine, mycophenolate, etanercept, methotrexate within 6 months of randomization, other immunosuppressive medications (including mitoxantrone, alemtuzumab, cladribine, pimecrolimus , IPP- 201101) at any time; total lymphoid irradiation or hematopoietic stem cell transplantation at any time; any biological therapy within 12 months of randomization - Steroids at a dose superior to the equivalent dose of 12.5mg/day or 25 mg on alternate day of oral prednisone or of pulsed 400mg/month of intravenous or intravenous methylprednisolone - Subject has received a live vaccination
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): To determine the efficacy of rituximab compared to placebo in reducing the proportion of patients with CIDP who worsen by at least one point in the INCAT score or two-points in the MRC sum-score or four points in the R-ODS score within six months after suspension of the treatment with immunoglobulins;Timepoint(s) of evaluation of this end point: The primary endpoint will be evaluated at month 12 after the start of treatment with rituximab;Main Objective: The primary objective of this study is to assess whether rituximab is effective in CIDP permitting to suspend immunoglobulin therapy without clinical worsening;Secondary Objective: The secondary objective is to evaluate whether treatment with rituximab may improve the response to therapy compared to placebo in patients treated with immunoglobulins and whether it may allow delay of the mean worsening time after discontinuation of immunoglobulin therapy. The exploratory objectives are the correlation between the response to rituximab therapy and the clinical form of CIDP and the presence of antibody reactivity against Ranvier node antigens. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To determine whether the treatment with rituximab to IVIg or SCIg in patients with CIDP may improve the disability (INCAT score and R-ODS score) and impairment (MRC sums-core for muscle strength) compared to placebo; To determine the efficacy of rituximab compared to placebo in reducing the number of patients with CIDP who worsen by at least one point in the INCAT score, two-points in the MRC sum-score or four points in the R-ODS score within 12 months and 18 months after suspension of the treatment with immunoglobulins; To determine the proportion of patients who suspend the treatment with rituximab or placebo for adverse events or for voluntary reasons or who develop adverse events in the 12 months following the start of treatment with rituximab; To compare the mean time for patients with CIDP treated with rituximab or placebo to worsen by at least one point in the INCAT score, two-points in the MRC sum-score or four points in the R-ODS score after suspension of the treatment with immunoglobulins; To determine whether the association of rituximab to IVIg or SCIg in patients with CIDP may improve compared to placebo the quality of life of the patients determined by SF-36 score after 6, 12, 18 and 24 months from the start of treatment with rituximab; Exploratory endpoint: To determine the difference between patients treated with rituximab or placebo in the mean variation of motor conduction block, negative distal CMAP amplitude, motor conduction velocity, distal and F-wave latencies in the two most relevant nerve between at the baseline and months 6, 12 and 24.; Exploratory endpoints: - To correlate the response to therapy with rituximab with the clinical form of typical or atypical CIDP - To correlate the response to therapy with rituximab in patients with CIDP with the presence of antibody reactivities against proteins at the node of Ranvier (contactin 1 and neurofascin 155);Timepoint(s) of evaluation of this end point: After 6, 12, 18 and | — |
Countries
Italy
Contacts
Public ContactProf. Eduardo Nobile-Orazio
IRCCS Istituto Clinico Humanitas
Outcome results
None listed