A Phase Id, Randomised, Double-Blind, Placebo-Controlled, Multiple-Dose Bridging Study To Evaluate The Pharmacokinetics, Safety, Tolerability, and Immunogenicity of XKH001 in Healthy Adult Caucasian Participants
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Primary Outcome 10
研究概览
简要总结
This is a Phase Id, randomised, double-blind, placebo-controlled, multiple-dose, bridging study conducted at a single Phase I clinical research unit in Australia. The study is designed to evaluate the pharmacokinetics, safety, tolerability, and immunogenicity of XKH001 following repeated subcutaneous administration in healthy adult Caucasian participants, and to provide an ethnic-bridging pharmacokinetic comparison with the prior Phase I dataset in Chinese participants, required for XKH001's global development programme.
详细描述
The study will consist of two cohorts of healthy adult Caucasian participants. Cohort 1 will receive XKH001 300 mg subcutaneously once every 4 weeks (Q4W) on Day 1, Day 29, and Day 57... Cohort 2 will receive XKH001 600 mg subcutaneously Q4W on Day 1, Day 29, and Day 57. Dosing will be initiated sequentially, with Cohort 1 (300 mg) dosed first, followed by Cohort 2 (600 mg). Dosing in Cohort 2 will not commence earlier than 21 days after the first participant in Cohort 1 receives the first dose and may proceed only following joint review of the available Cohort 1 safety data and unanimous agreement by the Sponsor's medical representative, the Medical Monitor, and the Principal Investigator A total of 16 healthy adult Caucasian participants will be enrolled in the study, with 8 participants per cohort. Within each cohort, participants will be randomised in a 3:1 ratio (6 active drug XKH001; 2 placebo) in a double-blind manner. Randomisation will be performed using a cohort-specific block randomisation schedule to maintain allocation concealment and treatment balance within each cohort. Enrolment will not be stratified by sex; however, at least 3 female participants will be enrolled in each cohort to ensure adequate female representation and to ensure that at least 1 female participant receives the investigational drug.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy participants who voluntarily provide written informed consent and can comply with all study procedures according to the protocol.
- •Male or female participants of Caucasian ethnicity(both biological parents and all four grandparents of Caucasian origin), 18-65 years of age (inclusive).
- •Body mass index (BMI) between 18.0-32.0 kg/m² (inclusive).
- •Vital signs, physical examination, clinical laboratory tests, and 12-lead electrocardiogram (ECG) within normal limits or considered not clinically significant by the investigator, with QTcF ≤450 ms.
- •No use of prescription or over-the-counter medications within 4 weeks prior to first dosing.
- •Participants must meet the sex- and reproductive-status-specific contraception and gamete-donation requirements specified in Appendix
- •Where contraception is required, the participant must agree to use the protocol-specified established effective contraception from the time of signing the informed consent form until 7 months after the last dose of study drug.
排除标准
- •Pregnant or breastfeeding women.
- •Any clinically significant disease within 5 years that could affect participation (gastrointestinal, renal, hepatic, pulmonary, neurology, Haematology, endocrine, oncology, metabolic, psychiatric, or cerebrovascular).
- •History of autoimmune disease, known hereditary immunodeficiency, or recurrent infections suggesting immunodeficiency.
- •Active infection requiring hospitalisation or IV antibiotics within 3 months, or clinically symptomatic bacterial, viral, or fungal infection within 4 weeks prior to first dosing.
- •Active or latent tuberculosis infection.
- •HBsAg positive, HCV antibody positive, syphilis antibody positive, or HIV antigen/antibody positive.
- •Live or attenuated vaccine within 4 weeks prior to dosing or planned during trial.
- •Participation in any clinical trial within 3 months or 5 half-lives of the investigational drug (whichever is longer) prior to dosing.
- •History of allergy to the investigational drug, any formulation component, or protein-based drugs.
- •Alcohol consumption >14 units/week within 6 weeks prior to screening, or alcohol-containing products within 1 day before dosing (1 unit = 8 g or 10 mL of pure alcohol).
- •Drug abuse or illicit substance use within 5 years, or positive urine drug screen(A positive cotinine result alone is not exclusionary).
- •Smoking history (>5 cigarettes/day) within 3 months prior to screening.
- •Blood donation or loss >450 mL within 8 weeks, or >200 mL blood donation or >300 mL blood loss within 1 month.
- •Unsuitable venous access or intolerance of venipuncture.
- •Prior exposure to any anti-IL-25 therapeutic agent, including XKH001 or any other investigational or approved therapeutic agent targeting IL-
- •Any other reason deemed unsuitable by the investigator.
研究组 & 干预措施
Cohort 1
Cohort 1 will receive 300 mg XKH001 Injection or XKH001 Placebo Injection
干预措施: XKH001 Placebo Injection (Drug)
Cohort 1
Cohort 1 will receive 300 mg XKH001 Injection or XKH001 Placebo Injection
干预措施: XKH001 Injection (Drug)
Cohort 2
Cohort 2 will receive 600 mg XKH001 Injection or XKH001 Placebo Injection
干预措施: XKH001 Injection (Drug)
Cohort 2
Cohort 2 will receive 600 mg XKH001 Injection or XKH001 Placebo Injection
干预措施: XKH001 Placebo Injection (Drug)
结局指标
主要结局
Primary Outcome 10
时间窗: Day 1, Day 29, and Day 57
Terminal elimination rate constant (λz,ss)
Primary Outcome 1
时间窗: Day 1, Day 29, and Day 57
Maximum observed serum concentration at steady state (Cmax,ss)
Primary Outcome 2
时间窗: Day 1, Day 29, and Day 57
Minimum observed serum concentration at steady state (Cmin,ss)
Primary Outcome 3
时间窗: Day 1, Day 29, and Day 57
Average serum concentration at steady state (Cavg,ss)
Primary Outcome 4
时间窗: Day 1, Day 29, and Day 57
Area under the serum concentration-time curve from time zero to the last quantifiable concentration at steady state (AUC0-t,ss)
Primary Outcome 5
时间窗: Day 1, Day 29, and Day 57
Area under the serum concentration-time curve from time zero to the theoretical infinite time at steady state (AUC0-inf,ss)
Primary Outcome 6
时间窗: Day 1, Day 29, and Day 57
Area under the serum concentration-time curve over one dosing interval at steady state (AUCtau)
Primary Outcome 7
时间窗: Day 1, Day 29, and Day 57
Time to maximum observed serum concentration at steady state (tmax,ss)
Primary Outcome 8
时间窗: Day 1, Day 29, and Day 57
Terminal elimination half-life at steady state (t½,ss)
Primary Outcome 9
时间窗: Day 1, Day 29, and Day 57
Mean residence time at steady state (MRTss)
Primary Outcome 11
时间窗: Day 1, Day 29, and Day 57
Percent of extrapolated area under the curve (%AUCex)
Primary Outcome 12
时间窗: Day 1, Day 29, and Day 57
Accumulation ratio based on Cmax and AUC (Rac)
Primary Outcome 13
时间窗: Day 1, Day 29, and Day 57
Apparent clearance at steady state (CLss/F)
Primary Outcome 14
时间窗: Day 1, Day 29, and Day 57
Apparent volume of distribution at steady state (Vz,ss/F)
Primary Outcome 15
时间窗: first dose administration through Day 169
Incidence, severity, seriousness, and relationship to study treatment of treatment-emergent adverse events (TEAEs)
Primary Outcome 16
时间窗: first dose administration through Day 169
Incidence, severity, seriousness, and relationship to study treatment of treatment-emergent serious adverse events (SAEs)
Primary Outcome 17
时间窗: first dose administration through Day 169
Incidence, severity, seriousness, and relationship to study treatment of treatment-emergent adverse drug reactions (ADRs)
Primary Outcome 18
时间窗: first dose administration through Day 169
Incidence, severity, seriousness, and relationship to study treatment of treatment-emergent suspected unexpected serious adverse reactions (SUSARs)
Primary Outcome 19
时间窗: first dose administration through Day 169
Incidence and severity of local injection-site reactions following subcutaneous administration of XKH001 or placebo
次要结局
- Secondary Outcome 1(Day 1, Day 29, and Day 57, and during follow-up visits on Day 85, Day 113, and Day 169.)
- Secondary Outcome 2(Day 1, Day 29, and Day 57, and during follow-up visits on Day 85, Day 113, and Day 169.)
- Secondary Outcome 3(Day 1, Day 29, and Day 57, and during follow-up visits on Day 85, Day 113, and Day 169.)