Rituximab in Chronic Inflammatory Demyelinating Polyradiculoneuropathy

NCT06325943 | Completed Phase 3

• 1 other identifier: CIDPRIT
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized double-blind controlled study of rituximab versus placebo in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) on chronic treatment with immunoglobulins. The primary objective of the study is to determine whether rituximab treatment is effective in preventing the disease from getting worse after stopping immunoglobulin treatment for six months in patients with CIDP. The secondary objective is to evaluate whether treatment with rituximab can improve the response to therapy compared to placebo in patients treated with immunoglobulins and whether it can allow to delay the mean time of worsening after discontinuation of immunoglobulin therapy. Exploratory objectives are the correlation between response to rituximab therapy and the clinical form of CIDP and the presence of antibody reactivity against node of Ranvier antigens. Intervention will be Rituximab or placebo, 1 g by intravenous infusion on day 1 and 15 after randomization and concomitant treatment for 6 months with intravenous or subcutaneous immunoglobulin at the same dosage as before randomization.

Conditions

Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Outcome Measures

Primary Outcomes (3)

• Inflammatory Neuropathy Cause and Treatment (INCAT) scale, range 0-10 points with higher values meaning more severe disability

  proportion of patients with CIDP who worsen by at least one point in the INCAT score within six months after suspension of six-month treatment with intravenous or subcutaneous immunoglobulin

  6 months

• Medical Research Council (MRC), range 0-60 with lower values meaning more severe disability

  proportion of patients with CIDP who worsen by at least two points in the MRC sum score within six months after suspension of six-month treatment with intravenous or subcutaneous immunoglobulin

  6 months

• Inflammatory Rasch-built Overall Disability Scale (I-RODS), range 0-48 with lower values meaning more severe disability

  proportion of patients with CIDP who worsen by at least four points in the I-RODS scale within six months after suspension of six-month treatment with intravenous or subcutaneous immunoglobulin

  6 months

Secondary Outcomes (5)

• Inflammatory Neuropathy Cause and Treatment (INCAT) scale, , range 0-10 points with higher values meaning more severe disability

  6,12,18 months

• Inflammatory Neuropathy Cause and Treatment (INCAT) scale, range 0-10 points with higher values meaning more severe disability

  12 months

• treatment suspension

  12 months

• time to worsening

  6 months

• Short Form Health Survey 36 (SF-36), range from 0 to 100, with a higher score defining a more favorable health state

  6,12,18 months

Other Outcomes (3)

• motor conduction block in the two most relevant nerves, range 0-100% with lower score defining lesser degree of impairment

  6 and 12 months

• clinical form

  6,12, and 18 months

• response to rituximab in patients with antinerve antibodies

  6, 12 and 18 months

Study Arms (2)

Treatment arm

ACTIVE COMPARATOR

Rituximab Patients will receive two doses of rituximab 1 g at two-week interval and one dose of rituximab 1 g at month 6

Drug: Rituximab

Placebo arm

PLACEBO COMPARATOR

Placebo Patients will receive two doses of placebo at two-week interval and one dose of placebo at month 6

Other: Placebo

Interventions

Rituximab DRUG

Patients will receive two doses of rituximab 1 g at two-week interval and one dose of rituximab 1 g at month 6

Treatment arm

Placebo OTHER

Patients will receive two doses of placebo at two-week interval and one dose of placebo at month 6

Placebo arm

Eligibility Criteria

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

You may qualify if:

• Subject is ≥ 18 years of age at Visit 1 (screening)
• Subject has a documented diagnosis of definite or probable CIDP according to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria 2010 (Joint Task Force of the EFNS and the PNS, 2010)
• Subject has an immunoglobulin-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 immunoglobulin 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 subcutaneous immunoglobulin (SCIg) or intravenous immunoglobulin (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 intravenous immunoglobulin, respectively, for stability in functioning between dosing. If the immunoglobulin 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 six month 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.

You may not qualify if:

• Subject has a current diagnosis or has a history of Type 1 or Type 2 diabetes mellitus
• Subject with immunoglobulin M (IgM) paraproteinemia with anti-myelin associated glycoprotein antibodies (MAG)
• Subject has Multifocal Motor Neuropathy with conduction block (MMN)
• Patient with a CIDP relapse or significant worsening of symptoms within 6 months of randomization
• 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 leukocyte count \<4000/mm3, lymphocyte count \< 800/mm3, platelet count \<100,000/mm3
• Subject has liver impairment defined as total or conjugated bilirubin \>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; gamma glutamyl-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 a severe immunocompromising condition 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)

Sponsors & Collaborators

• Istituto Clinico Humanitas: lead
• Ospedale Mondino di Pavia: collaborator
• University of Turin, Italy: collaborator
• Istituto Neurologico Carlo Besta di Milano: collaborator
• San Raffaele University Hospital, Italy: collaborator
• Università di Messina: collaborator
• Universita degli Studi di Genova: collaborator
• Istituto Di Ricerche Farmacologiche Mario Negri: collaborator
• Università di Napoli Federico II: collaborator

Study Sites (1)

IRCCS Istituto Clinico Humanitas

Rozzano, Italy

Location

Related Publications (1)

• Nobile-Orazio E, Cocito D, Manganelli F, Fazio R, Lauria Pinter G, Benedetti L, Mazzeo A, Peci E, Spina E, Falzone Y, Dalla Bella E, Germano F, Gentile L, Liberatore G, Gallia F, Collet-Vidiella R, Bianchi E, Doneddu PE. Rituximab versus placebo for chronic inflammatory demyelinating polyradiculoneuropathy: a randomized trial. Brain. 2025 Apr 3;148(4):1112-1121. doi: 10.1093/brain/awae400.

  PMID: 39658326 DERIVED

MeSH Terms

Conditions

Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Polyradiculoneuropathy; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a phase 3, multicenter, randomized, placebo-controlled, parallel-group, double-blind study

Study Record Dates

• First Submitted: May 17, 2023
• First Posted: March 22, 2024
• Study Start: April 1, 2019
• Primary Completion: May 30, 2023
• Study Completion: November 30, 2023
• Last Updated: March 26, 2024

Record last verified: 2024-03

Locations

IT (1)