A Randomized, Double-Blind, Placebo-controlled, Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, Pharmacodynamics and Clinical Activity of BBT001 Following Intravenous Administration in Adult Patients With Chronic Spontaneous Urticaria.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 48
- 试验地点
- 10
- 主要终点
- Number of participants with adverse events following multiple administration of BBT001
研究概览
简要总结
This is a Phase IIa, randomized, blinded, placebo controlled,Multiple-Ascending Dose study of BBT001 in adult patients with Chronic Spontaneous Urticaria.
详细描述
The study consists of below cohorts:
Cohort A1 (biologic-naïve): 450 mg BBT001 (n = 8) or placebo (n = 4) Cohort A2 (biologic-experienced): 450 mg BBT001 (n = 8) or placebo (n = 4) Cohort A3 (biologic-naïve) (optional): 900 mg BBT001 (n = 8) or placebo (n = 4) Cohort A4 (biologic-experienced) (optional): 900 mg BBT001 (n = 8) or placebo (n = 4)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female 18 to 75 years (inclusive) of age at time of consent. 2)Capped weight to be no more than 125 kg at screening.3)UAS7>=16; 4)Patients must have been on daily stable doses of H1-AH;5) Written informed consent obtained from the participant prior to performing any protocol-related procedures. For A2/A4 only: Participants who have received prior treatment with any biological products (e.g., omalizumab or dupilumab) . The last dose≥ 5 half-lives prior to randomization.
排除标准
- •1）Inducible urticaria ; 2） Diseases with possible symptoms of urticaria or angioedema such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis ；3） Presence of skin morbidities other than CSU that may interfere with the assessment of the study outcomes; 4)History of herpes simplex infection; 5 ）Serological abnormalities of infection at screening .
研究组 & 干预措施
Cohort A1:Placebo (450mg biologic naive)
A multiple ascending dose (MAD) of 450 mg BBT001 will be administered to patients with chronic spontaneous urticaria (CSU)who are naïve to biologic therapy.
干预措施: Placebo (Drug)
Cohort A1:placebo (450mg biologic experienced)
A multiple ascending dose (MAD) of 450 mg BBT001 will be administered to patients with chronic spontaneous urticaria (CSU) who are experienced to biologic therapy
干预措施: Placebo (Drug)
Cohort A3:Placebo (900mg biologic naive)
A multiple ascending dose (MAD) of 900 mg BBT001 will be administered to patients with chronic spontaneous urticaria (CSU) who are naïve to biologic therapy.
干预措施: Placebo (Drug)
Cohort A4:Placobo (900mg biologic experienced)
A multiple ascending dose (MAD) of 900 mg BBT001 will be administered to patients with chronic spontaneous urticaria (CSU) who are experienced to biologic therapy.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of participants with adverse events following multiple administration of BBT001
时间窗: - Up to Day 183 post first dose administration
Incidence, relatedness, and severity of adverse events graded per NCI CTCAE v6.0.
Number of participants with change in vital sign measurements following treatment administration.
时间窗: Up to Day 183 post first dose administratio
Blood pressure and heart rate will be assessed.
Number of participants with change in serum blood parameters.
时间窗: Up to Day 183 post first dose administration
Laboratory assessments include hematology, blood chemistry and coagulation test
Number of participants with change in physical examination following treatment administration
时间窗: Up to Day 183 post first dose administration
Physical examination will be assessed
Number of participants with change in 12-lead electrocardiogram (ECG) results measurements following treatment administration.
时间窗: Up to Day 183 post first dose administration
12-lead ECG will be tested at individual sites using sites' equipment and will be assessed.
次要结局
- Pharmacokinetics parameters- Time for maximum observed Concentration (Tmax)(At specified timepoints pre-dose and up to 183 days post first dose administration])
- Pharmacokinetics parameters- Area under the curve (AUC)(At specified timepoints pre-dose and up to 183 days post first dose administration)
- Pharmacokinetics parameters- Volume of distribution (Vz)(At specified timepoints pre-dose and up to 183 days post first dose administration)
- Pharmacokinetics parameters- maximum observed Concentration (Cmax)(specified timepoints pre-dose and up to 183 days post first dose administration)
- Pharmacokinetics parameters- Total clearance (CL)(At specified timepoints pre-dose and up to 183 days post first dose administration)
- Pharmacokinetics parameters- - Elimination Half-life (t1/2).(At specified timepoints pre-dose and up to 183 days post first dose administration)
- The immunogenicity of BBT001 is measured as the number and percentage of subjects who develop Anti-Drug Antibodies (ADA).(At specified timepoints pre-dose and up to 183 days post first dose administration)