Rituximab in Chronic Inflammatory Demyelinating Polyneuropathy: A Phase II Study

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Brief Title

Rituximab in Chronic Inflammatory Demyelinating Polyneuropathy: A Phase II Study

Official Title

Rituximab in Chronic Inflammatory Demyelinating Polyneuropathy: A Phase II Study

Brief Summary

      CIDP is a heterogeneous disease with variable responses to therapy. Recently, a distinctive
      subgroup of patients with serum autoantibodies to the paranodal proteins contactin and
      neurofascin have been identified. Although they present with active and serious disease,
      multiple clinical reports suggest that these patients can be cured with a treatment that
      depletes B cells and presumably eliminates pathogenic autoantibodies. However, beyond that
      subgroup of CIDP patients, which CIDP patients might benefit from Rituximab and B cell
      depletion is unknown. This Phase II study will treat 3 homogenous groups of 16 CIDP patients
      each with Rituximab in order to determine if there are subgroups that can be taken off
      current medications and put into long-term remission. The results from this study will be
      used to design a future larger trial. Biomarkers including paranodal antibodies, serum
      neurofilament light chains, anti-ganglioside antibodies will be obtained in order to learn
      about disease pathogenesis and possibly target therapy
    


Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score

Secondary Outcome

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

Condition

Chronic Inflammatory Demyelinating Polyneuropathy

Intervention

Rituximab

Study Arms / Comparison Groups

 IVIg/SCIg < 12 Months Arm
Description:  Patients with CIDP successfully treated with IVIg/SCIg for under 12 months.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

48

Start Date

November 2020

Completion Date

October 2025

Primary Completion Date

October 2023

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent obtained from subjects indicating that they understand the
             purpose of and procedures required for the study and are willing to participate

          2. Male or female, aged ≥18 years

          3. Documented diagnosis of CIDP according to the European Federation of Neurological
             Societies/Peripheral Nerve Society (EFNS/PNS) criteria 2010

          4. Must be willing to complete the study and return for follow-up visits.

          5. Men and women of reproductive potential must agree to use an acceptable method of
             birth control during treatment and for twelve months (1 year) after completion of
             treatment.

          6. Successfully treated CIDP patients. Data at or prior to the screening visit must show
             evidence that during the course of therapy either the INCAT score improved by 1 or
             more points or improvement occurred according to the physician opinion.

          7. CIDP disease stability is based on 2 visits that are 3 or more months apart
             documenting at or prior to the screening visit either the same INCAT score or
             unchanged CIDP status per physician opinion. The subject must be at the same dosage
             and frequency of CIDP therapy in between these 2 timepoints.

          8. Belonging to 1 of the following 3 treatment groups:

               1. IVIg/SCIg for under 12 months.

               2. IVIg/SCIg for more than 12 months.

               3. Corticosteroids for at least 6 months.

          9. Subject has an IVIg/SCIg or corticosteroid dependency confirmed by clinical
             examination in the 12 months before screening and documented in medical history (i.e.,
             that a decrease or withdrawal of treatment was attempted that resulted in a clinically
             relevant decrease in function)

         10. Stable dose of corticosteroid or IVIg/SCIg for 1 month prior to screening and no
             anticipated change in dosage or CIDP therapy from week 0 to week 24.

         11. Concurrent immunosuppressive agents (such as azathioprine, methotrexate, mycophenolate
             mofetil, or cyclosporine or cyclophosphamide or any other agent) are not allowed
             except if discontinued for at least 6 months prior to screening visit.

        Exclusion Criteria:

          1. Female subjects who are premenopausal and are

               1. pregnant on the basis of a serum pregnancy test,

               2. breast-feeding, or

               3. not using an effective method of double barrier (1 hormonal plus 1 barrier method
                  or 2 simultaneous barrier methods) or birth control (birth control pills, male
                  condom, female condom, intrauterine device, Norplant, tubal ligation, or other
                  sterilization procedures).

          2. Participation in another clinical study within 30 days before entering the study or
             during the study

          3. Employee or direct relative of an employee of the study site or Sponsor

          4. Other medical condition, laboratory finding, or physical exam finding that precludes
             participation

          5. A neuropathy of other causes, including:

               1. A motor syndrome that fulfils criteria for multifocal motor neuropathy (MMN) with
                  conduction block

               2. CIDP with monoclonal gammopathy of uncertain significance (CIDP-MGUS) or
                  monoclonal gammopathy associated with an oncologic diagnosis

               3. Neuropathies secondary to infections, disorders, or systemic diseases

               4. Drug-, biologic-, chemotherapy-, or toxin-induced peripheral neuropathy

               5. Hereditary demyelinating neuropathies

               6. Central demyelinating disorders (e.g. multiple sclerosis)

               7. Others, like polyneuropathy, lumbosacral radiculoplexus neuropathy

          6. Any chronic or debilitating disease, or central nervous disorder that causes
             neurological symptoms or may interfere with assessment of CIDP or outcome measures

          7. Cardiac insufficiency (New York Heart Association Classes III/IV), cardiomyopathy,
             significant cardiac arrhythmia requiring treatment, unstable or advanced ischemic
             heart disease, congestive heart failure or severe hypertension

          8. Subjects with current malignancy requiring chemotherapy and/or radiotherapy, or
             history of malignancy with less than 2 years of complete remission prior to screening.
             Exceptions are: adequately treated basal cell or squamous cell carcinoma of the skin,
             carcinoma in situ of the cervix, and stable prostate cancer not requiring treatment

          9. Patients on both corticosteroids and IVIg/SCIg

         10. Plasma exchange within the last 3 months of screen visit.

         11. Any prior treatment with a biologic (e.g. rituximab (MabThera®/Rituximab®),
             ocrelizumab (Ocrevus®), natalizumab (Tysabri®), alemtuzumab, TNF-α inhibitor)

         12. Abnormal laboratory parameters:

               1. creatinine >1.5 times the upper normal limit (UNL)

               2. hemoglobin (Hb) <10 g/dL

               3. absolute neutrophil count (ANC) <1000 cells/µl

               4. elevated liver enzymes (AST or ALT >2.5 x Upper Limit of Normal).

               5. platelets < 100,000/mL

         13. History of bone marrow hypoplasia, leucopenia, thrombocytopenia, significant anemia,
             clinical or laboratory evidence of immunodeficiency syndromes, that are not transient
             events or side effects related to a clinical procedure (i.e. plasmapheresis) and
             within one year of screening.

         14. Positive Hepatitis B or C serology (Hep B surface antigen and Hep C antibody). For
             patients who are negative for surface antigen [HBsAg] and positive for HB core
             antibody [HBcAb+], we will consult liver disease experts before starting and during
             treatment

         15. History of positive HIV (HIV conducted during screening if applicable)

         16. Receipt of a live vaccine within 4 weeks prior to randomization

         17. Contraindication to receiving Rituximab

         18. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
             antibodies

         19. History of recurrent significant infection or history of recurrent bacterial
             infections

         20. Known active bacterial, viral fungal mycobacterial, or other infection (including
             tuberculosis or atypical mycobacterial disease, but excluding fungal infections of
             nail beds) or any major episode of infection requiring hospitalization or treatment
             with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks
             prior to screening

         21. Lack of venous access

         22. History of drug, alcohol, or chemical abuse within 6 months prior to screening

         23. Any other disease, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that may affect the
             interpretation of the results or render the subject at high risk from treatment
             complications
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Mazen Dimachkie, MD, 913-945-9926, [email protected]



Administrative Informations


NCT ID

NCT04480450

Organization ID

R4CIDP


Responsible Party

Sponsor

Study Sponsor

University of Kansas Medical Center


Study Sponsor

Mazen Dimachkie, MD, Principal Investigator, University of Kansas Medical Center


Verification Date

July 2020