Rituximab Induced Remission in Patients With Chronic Inflammatory Demyelinating Polyneuropathy

NCT06714838 | Recruiting Phase 3 DMC

• 2 other identifiers: 2024.07942024-512506-25-00
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if the drug called rituximab causes remission in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The aim is to investigate this in two types of patients, those who are newly diagnosed, and those who are already being treated and are dependent on the current standard therapy: immunoglobulins administered through infusion (IVIg) or through injection (SCIg). The main questions this trial aims to answer are:

• To assess the effectiveness of rituximab
• Whether it is possible and useful to prescribe patients rituximab who experience a relapse after at least six months after their last rituximab treatment. Participants will:
• Receive the drug rituximab twice at the beginning of the trial and one additional time at six months.
• The newly diagnosed patients will also start another treatment called IVIg, which a nurse will administer every three weeks during the first three to six months.
• The patients who already being treated, will continue their regular treatment, until this is slowly reduced and stopped, during months three to six.
• Visit the clinic over the course of two years, during which they will have approximately 10 visits, for checkups and tests.
• Be asked to fill in questionnaires at each visit, and be asked to have their blood drawn four times.

Conditions

CIDP

Keywords

rituximab; remission; IVIg

Outcome Measures

Primary Outcomes (1)

• Remission at 52 weeks

  In order to assess efficacy of RTX: Remission at 52 weeks after start of RTX, i.e., no need of additional treatment after RTX treatment. For Group 1, remission is defined as sustained improvement, without the need for further treatment. Improvement will be defined as decrease in disability by at least the minimal clinical important difference (MCID) on the adjusted INCAT (aINCAT) disability scale and/or the Inflammatory-Rasch Overall Disability Scale (I-RODS). Sustained is defined as no deterioration after maximal improvement achieved in week 13 to 26. For Group 2, remission is defined as no change in disability (MCID) between start of Ig withdrawal and week 52.

  Baseline to 52 weeks

Other Outcomes (1)

• Stability on treatment at 104 weeks of follow-up.

  Baseline to 104 weeks

Study Arms (1)

Single arm: all patients receive rituximab

EXPERIMENTAL

All patients will receive rituximab at baseline (1000 mg) and after two weeks (1000 mg). Then, depending of whether the patient shows improvement in the following three to six months, the patient will receive another dose of rituximab (500 mg) at six months.

Drug: Rituximab (Mabthera)

Interventions

Rituximab (Mabthera) DRUG

Rituximab will be administered in a hospital setting in the course of one day. It will be given intravenously, at time points baseline, week 2 and week 26.

Single arm: all patients receive rituximab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• CIDP according to the EAN/PNS criteria (1)
• Untreated
• Men and women aged between 18 and 80 years
• Sufficient CIDP-related disability, as judged by treating physician to warrant IVIg and RTX treatment
• Capable of giving signed informed consent
• CIDP according to the European association of neurology/Peripheral nerve society (EAN/PNS) criteria (1) on maintenance treatment (stable dose/interval of at least 4 infusions or 3 months), including one of the following categories:
• patients with wear-off symptoms before next IVIg infusion captured by at least the minimal clinical important difference (MCID) on at least one outcome measure (see below)
• patients with a failed withdrawal attempt in the last 12 months captured by at least an MCID on at least one outcome measure (see below)
• patients with an increase of IVIg/SCIg dose/interval in the last 12 months leading to improvement by at least the MCID on at least one outcome measure, see below.
• The most commonly used MCID criteria, namely: 1) one point on the aINCAT disability score (1-10); 2) 4 points on a centile score on I-RODS (disability, 1-100); 3) 2 points on the MRC sum score (muscle strength, 0-60) and 4) 8 kPa on Vigorimeter (grip strength, single or both arms, variable range).
• Men and women aged between 18 and 80 years
• Capable of giving signed informed consent

You may not qualify if:

• Paranodopathy with demonstrated (paranodal) antibodies, previously considered part of CIDP spectrum (in these cases rituximab is preferred treatment)
• Use of drugs associated with a demyelinating neuropathy in the last six months.
• Known serious adverse events with previous IVIg or RTX treatment. Hypersensitivity to RTX or any component of the formulation. Hypersensitivity to the human immunoglobulins or to any of the excipients. Known selective IgA deficiency patients who developed antibodies to IgA.
• Positive hepatitis B and C serology suggesting active/untreated infection (HBsAg, anti-HB core en anti-HBs and HCV antibody (IgG))
• Ongoing immunosuppressive treatment for other indications.
• Immunosuppressive treatment other than (already discontinued) corticosteroids in last 6 months.
• IVIg interval of once every 6 weeks or more than 6 weeks (applies to Group 2 only)
• Obesity (BMI \> 35)
• Known active malignancy (not in remission), currently treated with chemotherapy or immunomodulatory drugs, or with a life expectancy of less than 1 year.
• History of recurrent/chronic infections
• Active, severe infections (such as tuberculosis, sepsis and opportunistic infections)
• Patients in a severely immunocompromised state Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
• Serious co-morbidity as judged by treating physician.
• Pregnancy or nursing mother; intention to become pregnant during the course of the study; female patients of childbearing potential either not using or not willing to use a medically reliable method of contraception for the entire duration of the study.
• No written informed consent

Sponsors & Collaborators

• Amsterdam University Medical Center (UMC), Location Academic Medical Center (AMC): lead
• Stichting Treatmeds: collaborator
• UMC Utrecht: collaborator
• Erasmus Medical Center: collaborator

Study Sites (1)

Amsterdam UMC

Amsterdam, 1105AZ, Netherlands

RECRUITING

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

Central Study Contacts

Filip Eftimov, MD PHD

CONTACT

+31205669111; f.eftimov@amsterdamumc.nl

Stevie Rozing, MD

CONTACT

s.c.e.rozing@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, MD PHD

Model Details: All patients will receive the same therapy

Study Record Dates

• First Submitted: November 4, 2024
• First Posted: December 4, 2024
• Study Start: October 16, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: December 4, 2024

Record last verified: 2024-12

Locations

NL (1)