CIDP - Chronic Inflammatory Demyelinating Polyneuropathy
Conditions
Brief summary
This is a multicenter, open-label, single-dose, dose-escalation study evaluating the safety and tolerability of intravenous (IV) KINE-101 in patients with corticosteroid-refractory chronic inflammatory demyelinating polyneuropathy (CIDP). On Day 1, subjects receive a single IV dose of KINE-101 at the assigned cohort level and are discharged on Day 3, approximately 48 hours after investigational product (IP) administration, once all required in-clinic assessments have been completed. Safety assessments (including dose-limiting toxicities \[DLTs\], adverse events, clinical laboratory tests, vital signs, physical examinations, and 12-lead ECGs), exploratory efficacy evaluations, and PK/PD assessments are conducted through Day 28 in accordance with the schedule of assessments. Exploratory efficacy assessments through Day 28 include changes from baseline in the following clinical measures: Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, Medical Research Council (MRC) total sum score, Inflammatory Rasch-Built Overall Disability Scale (I-RODS), Timed Up-and-Go (TUG) test, mean grip strength, and the Overall Neuropathy Limitations Scale (ONLS). Pharmacodynamic (PD) assessments include immunophenotyping of CD4+ T-cell subsets (CD4, CD25, FOXP3, CD39, CD69, CTLA-4, LAG-3, TNFR2, TIGIT, CCR5, and CXCR3); measurement of serum cytokines and immunoglobulins (IgM, IgG, IL-2, IL-6, IL-10, IL-17, IFN-γ, MCP-1, and TGF-β); evaluation of autoantibody and complement markers (antinuclear antibodies, anti-SM, anti-RNP, anti-SSA, anti-double-stranded DNA antibodies, and complement C4); and additional laboratory parameters related to systemic inflammation. Dose escalation follows a standard 3+3 design based on review of safety, including DLTs, in the preceding cohort. Three KINE-101 dose cohorts are planned: Cohort 1 (120 mg), Cohort 2 (240 mg), and Cohort 3 (360 mg). If safety and tolerability are deemed acceptable in a given cohort, enrollment proceeds sequentially to the next higher dose level.
Interventions
DRUGKINE-101
KINE-101 injection, 12.5 mg/mL, administered once intravenously on Day 1.
Sponsors
Kine Sciences Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Sequential dose escalation in single experimental arm with cohorts receiving 120 mg, 240 mg, or 360 mg.
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults aged ≥19 years at informed consent. * Diagnosed with CIDP and refractory to corticosteroid treatment for ≥3 months prior to enrollment, or corticosteroid treatment deemed inappropriate or cannot be continued for safety reasons. * Meets EAN/PNS 2021 criteria for typical CIDP: * Progressive or relapsing symmetrical motor weakness in arms and legs with sensory involvement in ≥2 limbs * Symptom duration ≥8 weeks * Reduced or absent tendon reflexes in all extremities * INCAT disability score ≥2 at screening (score of 2 must result solely from leg disability). * CIDP Disease Activity Status (CDAS) score ≥3 at screening. * Received IVIg ≥2 months prior to IP administration. * If the subject is of childbearing potential, agrees to use highly effective contraception for ≥28 days after IP administration. * Adequate venous access for IV administration and blood sampling. * Willing and able to comply with all study procedures.
Exclusion criteria
* Polyneuropathy due to other causes (e.g., MMN, MGUS with anti-MAG antibodies, hereditary neuropathies, POEMS syndrome, diabetic or systemic disease-related neuropathy, drug/toxin-induced neuropathy). * History of myelopathy or confirmed central demyelination. * Known allergy or hypersensitivity to the investigational product or its excipients. * Uncontrolled severe hepatic disease, CNS disorders, alcoholism, substance abuse, or psychiatric disorders. * Other medical conditions that better explain symptoms (e.g., stroke, CNS trauma, connective tissue disease). * Malignancy within 5 years, except adequately treated low-risk cancers. * Moderate to severe heart failure or severe cardiovascular disease (e.g., MI, ischemic stroke). * Moderate to severe substance or alcohol use disorder within 1 year. * Positive pregnancy test or planning pregnancy, breastfeeding, or gamete donation within 28 days post-IP. * Use of systemic immunosuppressants or immunostimulants within 5 half-lives prior to IP administration. * Plasma exchange within 8 weeks prior to IP administration. * Chronic infections or expected need for anti-infective treatment during the study. * Active hepatitis B or C infection or HIV positive. * Abnormal labs at screening: AST/ALT \>3×ULN, Hb \<9 g/dL, ANC \<1,500/μL, Platelets \<100×10³/μL. * Major surgery within 3 months or planned during study participation. * Investigator deems subject unsuitable for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AEs) | Day 1 to Day 28 | Incidence, severity, and relationship of treatment-emergent adverse events following a single intravenous dose of KINE-101. |
| Number of Participants with Clinically Significant Abnormal Hematology | Day 1 to Day 28 | Count of participants with clinically significant abnormal hematology findings (e.g., white blood cell count, hemoglobin, platelets, absolute neutrophil count), as defined per protocol. |
| Number of Participants with Clinically Significant Abnormal Clinical Chemistry | Day 1 to Day 28 | Count of participants with clinically significant abnormal clinical chemistry findings (e.g., ALT, AST, creatinine), as defined per protocol. |
| Number of Participants with Clinically Significant Abnormal Urinalysis | Day 1 to Day 28 | Count of participants with clinically significant abnormal urinalysis findings (e.g., protein/albumin, glucose, pH), as defined per protocol. |
| Number of Participants with Clinically Significant Abnormal Vital Signs | Day 1 to Day 28 | Count of participants with clinically significant abnormal vital sign findings (e.g., systolic or diastolic blood pressure, pulse rate, body temperature, respiratory rate), as defined per protocol. |
| Number of Participants with Clinically Significant Abnormal Physical Examination | Day 1 to Day 28 | Count of participants with clinically significant abnormal physical examination findings, as defined per protocol. |
| Number of Participants with Clinically Significant Abnormal Electrocardiogram | Day 1 to Day 28 | Count of participants with clinically significant abnormal electrocardiogram findings (e.g., PR interval, QRS duration, QT interval), as defined per protocol. |
Countries
South Korea
Contacts
STUDY_DIRECTORHanna Park
Kine Sciences Co., Ltd.
Outcome results
None listed