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A Study Investigating Intravenous Human Normal Immune Globulin (IGIV) 10% in Subjects With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

K

Kedrion Biopharma

Status and phase

Begins enrollment in 1 month
Phase 3

Conditions

Chronic Inflammatory Demyelinating Polyneuropathy

Treatments

Biological: Immune globulin (human) 10% solution for intravenous administration

Study type

Interventional

Funder types

Industry

Identifiers

NCT06752356
2024-518596-61-00
KB071 (Other Identifier)

Details and patient eligibility

About

The current study is being conducted to assess the efficacy and safety of KIg10 (Intravenous Human Immune globulin 10%) at two different dosages as maintenance therapy for Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) following 21 weeks of treatment.

Full description

This is a Double Blind, Randomized study. All subjects will enter a wash-out phase of up to 12 weeks, or until functional deterioration, defined as an increase of ≥1 point (worsening) in the adjusted INCAT disability score, is demonstrated. Eligible subjects will then be randomized in a 1:2 ratio to receive either 0.5 g/kg or 1.0 g/kg KIg10 at 3-weekly intervals for 21 weeks. Subjects who relapse during randomized treatment due to functional deterioration, based on the INCAT score, will be rescued with 2.0 g/kg KIg10 at 3-weekly intervals for 21 weeks.

Enrollment

161 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. Male or female, aged ≥18 years.

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

  3. Documented diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) consistent with the 2021 EAN/PNS criteria.

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

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

  6. Weakness of at least two limbs.

  7. Subjects 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. Pure sensory atypical and multivariant CIDP.

  2. Females who are pregnant, breastfeeding, unwilling to practice adequate contraception throughout the study or planning a pregnancy during the course of the study.

  3. IG-experienced subjects requiring an IGIV dosage of more than 1.3 g/kg/month OR SCIG pre-treated subjects requiring a SCIG dosage of more than 1.6 g/kg/month.

  4. Subjects who have previously failed to respond to IGIV or SCIG.

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

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

  7. Immunoglobulin M (IgM) paraproteinemia, including IgM monoclonal gammopathy with high titer antibodies to myelin-associated glycoprotein.

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

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

  10. Congestive heart failure (New York Heart Association (NYHA) Class III/IV), unstable angina, unstable cardiac arrhythmias, or uncontrolled hypertension

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

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

  13. 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 CKD-EPI equation at the time of screening.

  14. 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.

  15. 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.

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

  17. Known history of autoimmune nodo-paranodopathies causing IG treatment resistance.

  18. 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 defined as hemoglobin (Hgb) level of < 10.0 g/dL at screening.
  19. Ongoing/active infection with hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV Type 1/2 infection. Subjects with chronic hepatitis B or hepatitis C infection currently on treatment may participate as long as they have undetectable viral load within 12 months of screening date.

  20. Subjects who have received:

    1. Within 2 months before wash-out phase:

      • plasma exchange
      • 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

  21. Subjects who have received a hematopoietic stem cell transplant.

  22. Subjects on corticosteroids for the treatment of CIDP after being fully washed out. Subjects 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).

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

  24. Participation in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to screening visit or is scheduled to participate in another clinical study involving an IP or investigational device during the intended course of this study.

  25. History of acquired or inherited thrombophilic disorders. These will include the specific types of acquired or inherited thrombophilic disorders that could put subjects at risk of developing thrombotic events.

  26. Previous participation in this clinical study.

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

161 participants in 2 patient groups

1.0 g/kg dose group for 24 weeks
Experimental group
Description:
This group will receive, initial loading dose of 2.0 g/kg of Intravenous (IV) KIg10 (Immunoglobulin) infusion followed by 1.0 g/kg of IV KIg10 every 3 weeks.
Treatment:
Biological: Immune globulin (human) 10% solution for intravenous administration
0.5 g/kg dose group for 24 weeks
Experimental group
Description:
This group will receive, Initial loading dose of 2.0 g/kg of Intravenous (IV) KIg10 (Immunoglobulin) infusion will be given followed by 0.5 g/kg of IV KIg10 every 3 weeks.
Treatment:
Biological: Immune globulin (human) 10% solution for intravenous administration

Trial contacts and locations

0

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Central trial contact

Anna Lotti Suffredini; Esra Cinar-Jones

Data sourced from clinicaltrials.gov

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