A Randomized, Double-Blind, Placebo-controlled, Single- and Multiple-ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics,Immunogenicity, Pharmacodynamics and Clinical Activity of BBT002 in Healthy Volunteers and Participants With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) With or Without Comorbid Asthma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 64
- 试验地点
- 12
- 主要终点
- Number of participants with adverse events following single and multiple administration of BBT002
研究概览
简要总结
This study is a randomized, double-Blind, placebo-controlled, Single and Multiple-ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, Pharmacodynamics and Clinical Activity of BBT002 in Healthy Volunteers and Participants with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) with or without Asthma.
详细描述
The study consists of two parts:
- Part A (single dose in HVs in sequential ascending dose cohorts, SAD in HVs part)
- Part B (five repeated doses in patients with CRSwNP, MAD in patients part)
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
- 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
- •Part (A&B):
- •Age of 18-55 years (HVs), 18-75 years (patients)
- •Body mass index between 18-30 kg/m², capped at 120 kg
- •Negative pregnancy tests for women of childbearing potential
- •Willingness to refrain from alcohol consumption for 24 hours prior to each study visit
- •Non-smokers, healthy current smokers (≤5 cigarettes/day), or ex smokers
- •Key Inclusion Criteria (Part B only)
- •Participants with physician-diagnosed CRSwNP before screening.
- •SNOT-22 total score ≥30 at screening and randomization.
- •Documented systemic corticosteroid use (or contraindication/intolerance) within past 24 months.
- •Diagnosed asthma per GINA 2025, stable for ≥12 months. Stable on GINA Step 3 or higher therapy for 6 weeks before screening.
- •For the participants have comorbid asthma, they had to be stable using their regular asthma treatment.
排除标准
- •Part (A&B):
- •Positive viral serology for human immunodeficiency virus (HlV), hepatitis C virus (HCV), or hepatitis B (HBV)
- •Immunodeficiencies, autoimmune diseases, or cancer, history of conditions predisposing to infections
- •History of major metabolic, dermatological, liver, kidney, hematological or other significant disorders
- •Clinically relevant abnormal lab results, including low blood counts, liver enzymes, or abnormal kidney function
- •Positive drug/alcohol tests or abnormal vital signs at screening or Day -1
- •Abnormal Electrocardiogram(ECG) findings
- •History of drug/alcohol abuse in the past 2 years
- •History of severe allergic reactions or hypersensitivity
- •Key Exclusion Criteria for (Part B only):
- •Any sinus/nasal surgery (including polypectomy) within 6 months before screening, History of >2 prior sinus/nasal surgeries
- •Concurrent nasal conditions that may interfere with study assessments
- •Significant or unstable cardiovascular diseases
- •Recent clinically significant infection
结局指标
主要结局
Number of participants with adverse events following single and multiple administration of BBT002
时间窗: Part A- Up to Day 141; Part B - Up to Day 169 post first dose administration
Incidence, relatedness, and severity of AEs graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v6.0.
Number of participants with change in vital sign measurements following dose administration.
时间窗: Part A- Up to Day 141; Part B - Up to Day 169 post first dose administration
Changes in vital sign measurements, physical examination, clinical laboratory test findings, and 12-lead results.
Number of participants with change in physical examination following dose administration.
时间窗: Part A- Up to Day 141; Part B - Up to Day 169 post first dose administration
Physical examination will be assessed.
Number of participants with change in Laboratory assessments
时间窗: Part A- Up to Day 141; Part B - Up to Day 169 post first dose administration
Laboratory assessments include hematology, coagulation, clinical chemistry and urinalysis
Number of participants with change in 12-lead ECG readings
时间窗: Part A- Up to Day 141; Part B - Up to Day 169 post first dose administration
12-lead ECG will be assessed.
次要结局
- PK parameters- Area under the curve (AUC)(At specified timepoints pre-dose and up to 169 days post first dose administration)
- PK parameters- maximum observed concentration (Cmax)(At specified timepoints pre-dose and up to 169 days post first dose administration)
- PK parameters- Time for maximum observed Concentration (Tmax)(At specified timepoints pre-dose and up to 169 days post first dose administration)
- PK parameters- Volume of distribution (Vz)(At specified timepoints pre-dose and up to 169 days post first dose administration)
- PK parameters- Total clearance (CL)(At specified timepoints pre-dose and up to 169 days post first dose administration)
- PK parameters- - Elimination Half-life (t1/2)(At specified timepoints pre-dose and up to 169 days post first dose administration)
- The immunogenicity of BBT002 is measured as the number and percentage of subjects who develop Anti-Drug Antibodies (ADA).(At specified timepoints pre-dose and up to 169 days post first dose administration)