Badanie oceniające dożylne podawanie ludzkiej normalnej globuliny odpornościowej (IGIV) w stężeniu 10% pacjentom z przewlekłą zapalną polineuropatią demielinizacyjną (CIDP)

Inclusion Criteria:

1. Male or female, aged ≥18 years.

2. Written informed consent and authorization to access personal health information obtained independently from participants indicating that they understand the purpose of, and procedures required for, the study and are willing to participate.

3. Documented diagnosis of CIDP consistent with the 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) criteria.

4. Current or documented history of significant disability, as defined by an overall INCAT disability score between 2 and 9. A score of 2 must be exclusively from the lower extremities.

5. Participants are currently dependent on treatment with immunoglobulins, corticosteroids, or standard of care treatments for CIDP.

6. Weakness of at least two limbs.

7. Participants should be clinically stable 12 weeks prior to screening date as defined by:

   • without a worsening in INCAT score of ≥1 point, AND/OR without significant changes in clinical symptoms AND
   • without significant dose changes or requiring additional treatments.

Exclusion Criteria:

1. Patients' incapable of giving informed consent.

2. Pure sensory and other CIDP variants.

3. Females who are pregnant, breastfeeding, unwilling to practice effective birth control methods as defined in Appendix C throughout the study, or planning a pregnancy during the study.

4. IG-experienced participants requiring an IGIV dosage of more than 1.4 g/kg/month OR SCIG pre-treated participants requiring a SCIG dosage of more than 1.6 g/kg/month.

5. Participants who have previously failed to respond to IGIV or SCIG.

6. On screening date, a body mass index (BMI) > 35 kg/m2 or an IGIV dose that puts the patient at risk of fluid overload.

7. CIDP and any neuropathy of other causes not consistent with the 2021 EAN/PNS criteria including:

   1. Hereditary demyelinating neuropathies, such as a hereditary sensory and motor neuropathy (HSMN) (Charcot-Marie-Tooth [CMT] disease), and hereditary sensory and autonomic neuropathies (HSANs).
   2. Neuropathies secondary to infections, disorders, or systemic diseases such as Borrelia burgdorferi infection (Lyme disease), diphtheria, systemic lupus erythematosus, POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome, osteosclerotic myeloma, diabetic and non-diabetic lumbosacral radiculoplexopathy or neuropathy, lymphoma, and amyloidosis.
   3. Multifocal motor neuropathy (MMN).
   4. Drug-, biologic-, chemotherapy-, or toxin-induced peripheral neuropathy. Peripheral neuropathy induced by vitamin B12 deficiency.

8. Immunoglobulin M (IgM) paraproteinemia, including IgM monoclonal gammopathy with increased titers of antibodies to myelin-associated glycoprotein.

9. Central demyelinating disorders (e.g, multiple sclerosis) or severe myopathy.

10. Any chronic or debilitating disease, or central nervous disorder that causes neurological symptoms or may interfere with assessment of CIDP or outcome measures (e.g., severe arthritis, stroke, Parkinson's disease, and diabetic peripheral neuropathy) [participants with clinically diagnosed diabetes mellitus, who have adequate glycemic control with Hemoglobin A1C (HbA1C) of <7.5% at screening, and who agree to maintain adequate glycemic control during the study are allowed].

11. Congestive heart failure (New York Heart Association (NYHA) Class III/IV), unstable angina, unstable cardiac arrhythmias, or uncontrolled hypertension [i.e., diastolic blood pressure >100 mmHg and/or systolic blood pressure >160 mmHg]. If a single measure exceeds this limit, a triple repeat measurement may be performed and the average of the three measurements used.

12. History of deep vein thrombosis or thromboembolic events (e.g, cerebrovascular accident, pulmonary embolism) in the past 12 months.

13. Condition(s) which could alter protein catabolism and/or IgG utilization (e.g, protein-losing enteropathies, nephrotic syndrome).

14. Known history of chronic kidney disease, or glomerular filtration rate (GFR) of <60 milliliter per minute per 1.73 square meter (mL/min/1.73m2) estimated based on an established chronic kidney disease epidemiology collaboration (CKD-EPI) equation at the time of screening.

15. Active 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.

16. Hypersensitivity or adverse reactions (e.g, urticaria, breathing difficulty, severe hypotension, or anaphylaxis) to human blood products such as human IgG, albumin, or other blood components.

17. Known history of immunoglobulin A (IgA) deficiency.

18. Known history of autoimmune nodo-paranodopathies causing IG treatment resistance, including anti-neurofascin (NF) 186 antibodies and antibodies against paranodal proteins, such as NF155, contactin 1 (CNTN1), and contactin-associated protein 1 (CASPR1).

19. Abnormal laboratory values at screening:

    1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2.5x upper limit of normal (ULN)
    2. Platelet count <100,000 cells/µL.
    3. Absolute neutrophil count (ANC) <1000 cells/µL.
    4. Clinically significant anemia or hemoglobin (Hgb) level of < 10.0 g/dL at screening.

20. Ongoing/active infection with hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV Type 1/2 infection. Participants with chronic hepatitis B or hepatitis C infection currently on treatment may participate if they have undetectable viral load within 12 months of screening date.

21. Subjects who have received:

    1. Within 2 months before wash-out phase:

       • PE
       • change in treatment of methotrexate, azathioprine, or mycophenolate

    2. Within 3 months before wash-out phase: Efgartigimod alfa (Vyvgart)

    3. Within 5 months before wash-out phase: cyclophosphamide, interferon, tumor necrosis factor-alpha inhibitors, fingolimod, or any other immunosuppressive medications

    4. Within 12 months before wash-out phase: rituximab or alemtuzumab

22. Participants who have received a hematopoietic stem cell transplant.

23. Participants on corticosteroids for the treatment of CIDP after being fully washed out. Participants on maintenance doses of corticosteroid may be allowed, if treatment is for conditions unrelated to CIDP (doses usually below 20 mg/day prednisone or equivalent and where the dosage is unlikely to be tapered during the duration of the trial may be allowed for indications other than CIDP).

24. Any disorder or condition that in the investigator's judgment may impede the participant's participation in the study, pose increased risk to the participant, or confound the results of the study.

25. Participation in another clinical study involving an investigational medicinal product (IMP) or investigational device within 30 days prior to screening visit or within 5 half-lives of the IMP under investigation or is scheduled to participate in another clinical study involving an IMP or investigational device during the intended course of this study.

26. History of acquired or inherited thrombophilic disorders. These will include the specific types of acquired or inherited thrombophilic disorders that could put participants at risk of developing thrombotic events. Examples include, but are not restricted to:

    1. Hereditary thrombophilia, examples include

       • Factor V Leiden mutation.
       • Prothrombin 20210A mutation.
       • Protein C deficiency.
       • Protein S deficiency.
       • Antithrombin deficiency.

    2. Acquired thrombophilias, examples include:

       • Antiphospholipid antibody syndrome.
       • Activated protein C Resistance acquired.
       • Homocysteinemia.

27. Previous participation in this clinical study, except for participants who withdrew consent during the washout phase, prior to randomization.

28. Any other factor that, in the opinion of the investigator, would prevent the subject from complying with the requirements of the protocol.