A Proof of Concept Study With Rituximab in Patients With CIDP Not Responding to Conventional Immune Therapy

NCT05877040 | Unknown Phase 2

• 1 other identifier: RF-2016-02361887
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic and often disabling neuropathy that often responds to immune therapies. A few phenotypes have been identified even if it is unclear whether they are variants of CIDP or different diseases considering their relatively different responses to therapy. Antibodies against proteins at the node of Ranvier, including contactin 1 and neurofascin 155, have been reported in up to 10% of the patients and were associated to a poor response to CIDP therapy but a positive response to Rituximab supporting the heterogeneity of CIDP. We will examine these antibodies in a large population of Italian CIDP patients included in a Database and correlate their presence with the clinical and electrophysiological features of the neuropathy, its progression and response to therapy. We will perform an open label prospective therapeutic study with Rituximab in patients with CIDP not responsive to conventional immune therapies and will correlate the response to therapy to the clinical phenotype and the presence of anti-neural antibodies.This may lead to a more appropriate choice of therapy in CIDP avoiding the use of expensive and possibly ineffective therapy. We will also collect the biological samples (serum and when available CSF) of the patients with CIDP and store them to allow the formation of a biological bank that may be used in future immunological studies to clarify the pathogenesis a of the disease and possibly to identify biomarkers of the disease and of response to therapy. This study will permit to collect a sufficiently large number of adequately and homogeneously examined patients with CIDP, with different antibody reactivities and with unsatisfactory response to therapy. This will permit to have sufficiently large number of patients to perform an open-label study with Rituximab whose efficacy has been so far reported only in anecdotal reports on small number of patients.

Conditions

Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Outcome Measures

Primary Outcomes (3)

• Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Scale

  The proportion of patients with CIDP not responsive to conventional immune therapies that improve after therapy with rituximab

  6 months

• Medical Research Council sum score

  The proportion of patients with CIDP not responsive to conventional immune therapies that improve after therapy with rituximab

  6 months

• Inflammatory Rasch-built Overall Disability Scale (I-RODS)

  The proportion of patients with CIDP not responsive to conventional immune therapies that improve after therapy with rituximab

  6 months

Secondary Outcomes (7)

• Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Scale

  12 months

• Medical Research Council sum score

  12 months

• Inflammatory Rasch-built Overall Disability Scale (I-RODS)

  12 months

• Treatment discontinuation

  12 months

• Duration of clinical improvement after therapy with rituximab

  24 months

Study Arms (1)

Treated

EXPERIMENTAL

Drug: Rituximab

Interventions

Rituximab DRUG

Open label proof-of-concept study with intravenous Rituximab, given at the dose of 1g in one day, followed by the same dose after two weeks

Treated

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 Visit1 (screening) and who signed the informed consent form for the study
• 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 not improved after and adequate dose of therapy with intravenous immunoglobulins (IVIg) corresponding to at least 2 g/kg monthly for two months, steroids corresponding to the equivalent of at least 1 mg/kg daily of oral prednisone for two months or a course of at least 4 plasma exchanges within two weeks.
• Subject can take steroids at the maximum dosage equivalent to 25 mg/day of prednisone or pulsed 600 mg/monthly of methylprednisolone as far as the dosage has not been increased (+ 20%) in the previous 6 months and has not determined a satisfactory response to therapy.
• Female subjects of childbearing potential according with the CTFG guidelinesa must have a negative serum pregnancy test and agree to use a highly effective method of birth control in accordance with the CTFG guidelinesb during the study and for a period of 12 months after their last dose of study drug.
• Male subject, when sexually active, with a partner of childbearing potential according with the CTFG guidelinesa must be willing to use a highly effective method of birth control in accordance with the CTFG recommendationsb during the study and for 12 months after the final administration of rituximab.

You may not qualify if:

• \. Female who is pregnant or lactating 6. Subjects with any medical or psychiatric condition (acute or chronic) that, in the opinion of the investigator, could harm the subject or would compromise the subject's ability to participate in the study.
• \. Subjects with congestive heart failure or a moderate or severe impairment of cardiac function 8. Subjects with renal impairment defined as: serum creatinine \> 1.4 mg/dL for females and 1.5 mg/dL for males 9. Subjects with an absolute leukocyte count \<4000/mm3, lymphocyte count \<800/mm3, platelet count \<100,000/mm3 10. Subjects with 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 11. Subjects with 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 family history of primary immunodeficiency 13. Subject has a clinically 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.
• \. 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 has received a live vaccination within 8 weeks prior to the baseline visit or intends to have live vaccination during the course of the study or within 7 weeks following the final dose of rituximab.

Sponsors & Collaborators

• Istituto Clinico Humanitas: lead

Study Sites (1)

Istituto Clinico Humanitas

Rozzano, Milano, 20089, Italy

Location

Related Publications (1)

• Doneddu PE, Cocito D, Fazio R, Benedetti L, Peci E, Liberatore G, Falzone YM, Germano F, Gallia F, Giannotta C, Lleixa C, Bianchi E, Nobile-Orazio E. Prospective open-label trial with rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy not responding to conventional immune therapies. J Neurol Neurosurg Psychiatry. 2024 Aug 16;95(9):838-844. doi: 10.1136/jnnp-2023-332844.

  PMID: 38729746 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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2023
• First Posted: May 26, 2023
• Study Start: June 1, 2019
• Primary Completion: March 30, 2023
• Study Completion: September 30, 2023
• Last Updated: May 26, 2023

Record last verified: 2023-05

Locations

IT (1)