A Study Investigating Intravenous Human Normal Immune Globulin (IGIV) 10% KIg10 (QIVIGY) in Subjects With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

A Double-blind, Randomized, Multi-Center Study Investigating Efficacy and Safety of Two Different Dosages of Intravenous Human Normal Immune Globulin (IGIV) 10% KIg10 (QIVIGY) in Participants With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Inflammatory Demyelinating Polyneuropathy
• Intervention / Treatment: Biological: Immune globulin (human) 10% solution for intravenous administration

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 161
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Anna Lotti Suffredini; Phone Number: +39 338 6827568; Email: a.lotti@kedrion.com
• Study Contact Backup: Name: Esra Cinar-Jones; Phone Number: +44 7551 563340; Email: e.cinarjones@kedrion.com

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33613
      • Recruiting
      • USF Health - Morsani Center for Advanced Healthcare
      • Principal Investigator: Kathleen Murray
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Recruiting
      • Dartmouth-Hitchcock Medical Center
      • Principal Investigator: Victoria Lawson
  • Texas
    • El Paso, Texas, United States, 79912
      • Recruiting
      • Advanced Neurology Epilepsy and Sleep Center/ANESC Research
      • Principal Investigator: Aamr Herekar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1.0 g/kg dose group for 24 weeks; 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.	Biological: Immune globulin (human) 10% solution for intravenous administration; Kedrion intravenous immunoglobulin (IVIg) 10%; Other Names: KIg10
Experimental: 0.5 g/kg dose group for 24 weeks; 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.	Biological: Immune globulin (human) 10% solution for intravenous administration; Kedrion intravenous immunoglobulin (IVIg) 10%; Other Names: KIg10

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of 1.0 g/kg KIg10 in the treatment of adult subjects with active CIDP	The proportion of responders in the 1.0 g/kg KIg10 arm, at week 24 relative to Randomization Baseline week 0, based on the adjusted INCAT disability score. A responder is defined as having a ≥1 point decrease (improvement) in the adjusted INCAT score at week 24 relative to adjusted INCAT score at randomization baseline.	From Baseline upto 24 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of 0.5 g/kg KIg10 in the treatment of adult subjects with active CIDP	The proportion of responders in the 0.5 g/kg KIg10 arm at week 24 relative to randomization baseline, based on the adjusted INCAT disability score. A responder is defined as having a ≥1 point decrease (improvement) in the adjusted INCAT score at week 24 relative to adjusted INCAT score at randomization baseline.	From Baseline upto 24 weeks of treatment
Proportion of responders (Week 24 vs Baseline) in both dose groups	Proportion of responders in both dose groups based on Grip Strength and I-RODs	From Baseline upto 24 weeks of treatment
Proportion of responders in rescued subjects	Proportion of responders in rescued subjects based on grip strength, I-RODS scores, adjusted INCAT disability score	End of Treatment vs onset of rescue treatment
Improvers based on the MRC-sumscore	Improvers by a change of 4 points in both dose groups (week 24 versus baseline) based on MRC-sumscore	From Baseline upto 24 weeks of treatment
Mean Change in MRC-sumscore	Mean change in MRC-sumscore for both dose groups at week 24 vs baseline	From Baseline upto 24 weeks of treatment
Mean Change in MRC-sumscore for rescued subjects	Mean change in MRC-sumscore for rescued subjects from End of Treatment versus onset of rescue treatment	End of Treatment vs onset of rescue treatment
Disease Related QoL (CAPPRI) for each dose level	For each dose level the Chronic Acquired Polyneuropathy Patient Reported Index (CAPPRI) will be analysed for disease related QoL	From Baseline upto 24 weeks of treatment
Mean change in I-RODS	For each dose level, mean change from randomization baseline (visit 2, week 0) to end of study (visit 10, week 24) in Inflammatory-Rasch-built Overall Disability Scale (I- RODS) score	From Baseline upto 24 weeks of treatment
Mean change in I-RODS for rescued subjects	Mean change to the end of treatment assessments prior to onset of rescue treatment, in Inflammatory-Rasch-built Overall Disability Scale (I- RODS) score for rescued subjects	End of Treatment vs onset of rescue treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events	Assess Safety and Tolerability of KIg10	From Baseline upto 25 weeks
The proportion of patients experiencing at least one adverse event.	Assess Safety and Tolerability of KIg10	From Baseline upto 25 weeks

Collaborators and Investigators

• Sponsor: Kedrion S.p.A.
• Investigators: Study Chair: Lakshmi Deshpande, Kedrion S.p.A.

Publications and helpful links

General Publications

• Hughes RA, Donofrio P, Bril V, Dalakas MC, Deng C, Hanna K, Hartung HP, Latov N, Merkies IS, van Doorn PA; ICE Study Group. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. Lancet Neurol. 2008 Feb;7(2):136-44. doi: 10.1016/S1474-4422(07)70329-0.

Helpful Links

• Lewis et al. Chronic Inflammatory Demyelinating Polyneuropathy, National Organization for Rare Disorders, Updated 01Oct2024

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): December 20, 2027
• Study Completion (Estimated): December 27, 2027

Study Registration Dates

• First Submitted: December 16, 2024
• First Submitted That Met QC Criteria: December 27, 2024
• First Posted (Actual): December 30, 2024

Study Record Updates

• Last Update Posted (Actual): August 6, 2026
• Last Update Submitted That Met QC Criteria: August 5, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Intravenous; Chronic Inflammatory Demyelinating Polyneuropathy; CIDP; Human Immunoglobulin; KIg10; QIVIGY
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Peripheral Nervous System Diseases; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Polyneuropathies; Polyradiculoneuropathy; Pathological Conditions, Signs and Symptoms; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Amino Acids, Peptides, and Proteins; Proteins; Pharmaceutical Preparations; Therapeutics; Drug Administration Routes; Drug Therapy; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Immunoglobulins; Administration, Intravenous; Solutions
• Other Study ID Numbers: KB071 (Other Identifier: Kedrion S.p.A)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Publishing of data and IPD that underlie results in the publication will be determined at study completion to comply with ICJME minimum requirements.
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No