1314-1 Kyokushi Kawabe, Kikuchi-shi, Kumamoto, Japan
+81-968-37-4073
rinkai-jrct@kmbiologics.com
Yamashita Masatoshi
KM Biologics Co., Ltd.
1314-1 Kyokushi Kawabe, Kikuchi-shi, Kumamoto, Japan
+81-968-37-4073
rinkai-jrct@kmbiologics.com
Not Recruiting
May. 10, 2024
June. 17, 2024
30
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
(1) CIDP patients only: Patients aged 18 years or older at the time of informed consent
(2) MMN patients only: Patients aged 16 years or older at the time of informed consent
(3) CIDP patients only: Patients diagnosed with CIDP as defined in the 2021 EAN/PNS Guideline (excluding patients with possible CIDP)
(4) MMN patients only: Patients diagnosed with MMN as defined in the 2010 EFNS/PNS Guideline (excluding patients with possible MMN)
(5) Patients with progressive or recurrent CIDP (acute treatment cohort) or MMN (acute treatment cohort) (regardless of history of treatment with IVIg/SCIg)
(6) Patients with CIDP (maintenance therapy cohort): Patients on IVIg/SCIg maintenance therapy who have responded to IgG administration (Patients receiving IVIg 0.4 to 1.2 g/kg every 2 to 6 weeks for the past 12 weeks from the time of eligibility confirmation or SCIg 80 to 480 mg/kg every 1 to 2 weeks for the past 12 weeks from the time of eligibility confirmation)
(7) Patients with MMN (maintenance therapy cohort): Patients on IVIg maintenance therapy who have responded to IgG administration (i.e., have previously shown partial or complete improvement in neurological symptoms and disabilities) (Patients receiving IVIg 0.4 to 1.2 g/kg every 2 to 6 weeks for the past 12 weeks from the time of eligibility confirmation)
(8) Patients with CIDP (acute treatment cohort): Patients with an INCAT (Inflammatory Neuropathy Cause and Treatment) score between 2 and 9 of disability at the time of eligibility confirmation (but with a lower limb disability score of 2 or more, if the upper limb disability score is 1)
(9) Patients with CIDP (maintenance therapy cohort): Patients with an INCAT score between 0 and 7 at the time of eligibility confirmation and a previous disability with an INCAT score between 2 and 9 (but with a lower limb disability score of 2 or more, if the upper limb disability score is 1)
(10) In the case of using therapeutic agents * for CIDP and MMN within 30 days prior to eligibility confirmation, the patients who continue without adding and increasing dosage and require treatment with the test product
*Immunosuppressants including steroids, azathioprine, tacrolimus, cyclosporine, cyclophosphamide, methotrexate, mycophenolate mofetil, fingolimod, eculizumab
Patients with CIDP
(1) Patients with sensory CIDP
(2) Patients with autoimmune nodopathy
(3) Patients with autoimmune/inflammatory neuropathy such as multifocal motor neuropathy (MMN), Guillain-Barre syndrome, POEMS syndrome, IgM paraproteinemia including MAG antibody-associated neuropathy
(4) Patients with hereditary neuropathy such as Charcot-Marie-Tooth disease, hereditary sensory and autonomic neuropathy (HSAN)
(5) Patients with neuropathy secondary to internal diseases such as diabetes mellitus, cancer, collagen disease, amyloidosis, or infection such as Borrelia burgdorferi infection (Lyme disease), diphtheria (Eligible if there is no diabetic neuropathy, HbA1c level is stable and blood glucose control can be maintained appropriately)
(6) Patients with drugs, biological products, chemotherapy or toxicant induced neuropathy
Patients with MMN
(7) Patients with CIDP
(8) Patients with other neuromuscular diseases (e.g., hereditary motor neuropathy, motor neuron disease, neuromuscular junction disease, muscle disease, diabetic neuropathy, cervical spondylosis, lumbar spondylosis, hereditary neuropathy with liability to pressure palsies, peripheral nerve tumor, vasculitic neuropathy, sarcoid neuropathy, etc.). However, patients with those diseases that are considered NOT to affect outcomes or evaluations during the study in the investigator's opinion can be enrolled.
Patients with CIDP/MMN
(9) Patients who have received maintenance therapy with IVIg/SCIg for more than 52 weeks (maintenance therapy cohort only) (however, patients who received maintenance therapy with IVIg/SCIg for more than 52 weeks may also be enrolled if immunoglobulin administrations are considered necessary based on medical judgment).
(10) Patients with central demyelinating diseases such as multiple sclerosis
(11) Patients with chronic illnesses or central nervous system disorders (e.g. stroke, Parkinson's disease, amyotrophic lateral sclerosis, etc.) that may cause neurological symptoms or signs. However, patients with those diseases that are considered NOT to affect outcomes or evaluations during the study in the investigator's opinion can be enrolled.
(12) Patients who have an active malignancy requiring chemotherapy and/or radiation therapy, or have a medical history of malignancy and have been in complete remission for less than 2 years prior to eligibility confirmation. Exceptions to this exclusion criterion are appropriately treated basal cell or squamous cell carcinoma of the skin, intraepithelial carcinoma of the cervix, and stable prostate cancer not requiring treatment.
(13) For the most recent IVIg treatment, those who received >1.2 g/kg and <= 2.4 g/kg IVIg treatment within 9 weeks before eligibility confirmation, >=0.75 g/kg and <=1.2g/kg IVIg treatment within 6 weeks, or <0.75 g/kg within 3 weeks (excluding patients with CIDP and MMN, (both in the maintenance therapy cohort)). Otherwise, blood IVIg level* is >=0.375 g/kg at the time of eligibility confirmation.
*Blood IVIg level is calculated based on the dosage of IVIg treatment within 15 weeks before eligibility confirmation and its half-life (21 days).
(14) Patients who received SCIg in excess of 480 mg/kg as a single dose 4-5 weeks (22-35 days) prior to eligibility confirmation, patients who received SCIg in excess of 240 mg/kg as a single dose (480 mg/kg total) 3-5 weeks (15-35 days) prior to eligibility confirmation, patients who received SCIg in excess of 120 mg/kg as a single dose (480 mg/kg total) 2-5 weeks (8-35 days) prior to eligibility confirmation (but must not have received SCIg 1 week (1-7 days) prior to eligibility confirmation) (excluding patients with CIDP (maintenance therapy cohort) and MMN)
(15) Patients with heart failure, cardiomyopathy, severe arrhythmia requiring treatment, or ischemic heart disease
(16) Patients who have a medical history of pulmonary embolism, deep vein thrombosis or thromboembolic event in the past 12 months from the time of eligibility confirmation
(17) Patients with severe liver disease (alanine aminotransferase (ALT) level or aspartate aminotransferase (AST) level > 3 times the upper limit of reference (ULN)) or severe kidney disease (creatinine level > 1.5 times the upper limit of reference)
(18) Patients with severe anemia that interferes with repeated blood sampling in the clinical trial or whose hemoglobin (Hb) level < 10.0 g/dL at the time of eligibility confirmation
(19) Patients with severe hypersensitivity including urticaria, dyspnea, headache, hypotension or anaphylaxis, or a history of severe adverse reactions following administration of human blood products (IgG, albumin and other blood components)
(20) Patients with any of the following diseases/conditions:
a) IgA deficiency
b) anti-IgA antibodies
c) hypersensitivity to IgA
(21) Patients with an abnormal laboratory value which meets any of the following criteria at the time of eligibility confirmation
a) Platelet count < 100,000/microlitre
b) Absolute neutrophil count (ANC) < 1000/microlitre
(22) Patients who are positive for human immunodeficiency virus (HIV) type 1/2 or hepatitis B/C virus at the time of eligibility confirmation
(23) Patients who have received plasma exchange therapy within 3 months prior to eligibility confirmation
(24) Patients who had a dose increase or added any of the following therapeutic agents* within 30 days prior to eligibility confirmation (Except for external use)
* Immunosuppressants including steroids, azathioprine, tacrolimus, cyclosporine, cyclophosphamide, methotrexate, mycophenolate mofetil, fingolimod, eculizumab
(25) Patients who have been treated with rituximab within 6 months prior to eligibility confirmation
(26) Patients with any disability or medical condition that is judged by the principal investigator or subinvestigator to interfere with the patient's participation in the study, to pose a significant risk to the patient or to be confounding to the outcome of the study
(27) Lactating women, pregnant women, women/men planning to become pregnant, or women/men who have no intention to use an effective contraceptive during this study
(28) Patients who have participated in another study and received other investigational products or devices within 30 days prior to eligibility confirmation, or who are scheduled to participate in another study during the participation period in this study using other investigational products or devices
(29) Patients who are family members of the principal investigator or the subinvestigator, or employees of this study site and the sponsor
(30) Patients with a history of drug or alcohol abuse in the past 5 years from the time of eligibility confirmation
(31) Patients who are unable to understand or who are not willing to comply with this study
16age old over
No limit
Both
Chronic inflammatory demyelinating polyradiculoneuritis and multifocal motor neuropathy
Patients with CIDP/MMN
1. Acute treatment
GGL is administered as human immunoglobulin at a dose of 400 mg (4 mL)/kg body weight intravenously for 5 consecutive days. If the patient meets the criteria* for the second course of treatment, GGL is administered as human immunoglobulin at a dose of 400 mg (4 mL)/kg body weight intravenously for 5 consecutive days at 4 weeks after the start of treatment.
*Second course administration criteria: INCAT total score (patients with CIDP) or MRC total score (patients with MMN) unchanged or worsened compared to before the start of treatment at 4 weeks after the start of treatment. The INCAT score is evaluated with the adjusted INCAT score.
2. Maintenance therapy
GGL is administered as human immunoglobulin at a dose of 1000 mg (10 mL)/kg body weight intravenously for 1 day or 500 mg (5 mL)/kg body weight intravenously for 2 consecutive days. Thereafter, GGL is administered every 3 weeks in the same regimen.
Patients with CIDP
- Proportion of patients with improvement in the adjusted INCAT score after the first course of acute treatment
- Proportion of patients with worsening on the adjusted INCAT score during the first phase of maintenance therapy
Patients with MMN
Medical Research Council (MRC) sum scores and changes from baseline in the MRC scores in the first course of acute treatment and in the first phase of maintenance therapy
[Efficacy]
Patients with CIDP
- MRC sum scores and changes from baseline in the first course of acute treatment and the first phase of maintenance therapy
- Proportion of patients with improvement in the adjusted INCAT score after the second course of acute treatment
- Rasch-built Overall Disability Scale (R-ODS) scores and changes from baseline in the first course of acute treatment and in the first phase of maintenance therapy
- INCAT Sensory Sum scores (ISS) and changes from baseline in the first course of acute treatment and in the first phase of maintenance therapy
- Time to worsening of the adjusted INCAT score during the first phase of maintenance therapy
Patients with MMN
- Guy's Neurological Disability Scale (GNDS) sum scores and changes from baseline in the first course of acute treatment and in the first phase of maintenance therapy
-Time to worsening of MRC sum scores during the first phase of maintenance therapy
Patients with CIDP/MMN
- Maximum grip strength (Martin hand dynamometer) and changes in grip strength from baseline in the first course of acute treatment and in the first phase of maintenance therapy
- Compound muscle action potential (CMAP) amplitude following stimulation at the most severely affected proximal motor nerve site and changes in CMAP amplitude from baseline during the first course of acute treatment and during the first phase of maintenance therapy
- Serum IgG levels and changes from baseline during the first course of acute treatment and during the first phase of maintenance therapy
KM Biologics Co., Ltd.
Ministry of Health, Labour and Welfare
Not applicable
Institutional Review Board of Hyogo Medical University Hospital
