Multi-Center, Open-label, Single Dosing, Dose-Ascending, Phase 1 Study to Evaluate the Safety and Tolerability of KINE-101 in Patients With CIDP (Chronic Inflammatory Demyelinating Polyneuropathy) Refractory to Corticosteroid Treatment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Incidence of Adverse Events (AEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
KINE-101 120mg
Subjects received a single intravenous dose of KINE-101 120 mg.
干预措施: KINE-101 (Drug)
KINE-101 240 mg
Subjects received a single intravenous dose of KINE-101 240 mg.
干预措施: KINE-101 (Drug)
KINE-101 360 mg
Subjects received a single intravenous dose of KINE-101 360 mg.
干预措施: KINE-101 (Drug)
结局指标
主要结局
Incidence of Adverse Events (AEs)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
未报告次要终点