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 Patients With COPD or CRSwNP
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 286
- 试验地点
- 15
- 主要终点
- Number of participants with change in Laboratory assessments
研究概览
简要总结
Randomized study of single and multiple doses of BBT002 in healthy volunteers and in adult patients with chronic obstructive pulmonary disease (COPD) or chronic rhinosinusitis with nasal polyps (CRSwNP).
详细描述
This study a is a randomized, double-blinded, placebo-controlled single (SAD) and multiple-ascending dose (MAD) study to evaluate safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics, and exploratory clinical activity of BBT002 in healthy volunteers (HVs) and in adult patients with COPD or CRSwNP. BBT002 is a drug candidate being developed for the treatment of COPD or CRSwNP. BBT002 will be given by intravenous injection or subcutaneous injection.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •(Parts A, B, C, D, E, F, and G)
- •Age 18-65 years for HVs (Parts A, B, and E); age 35-80 years for patients with COPD (Parts C and F,); age 18-80 for patients with CRSwNP (Parts D and G)
- •Body mass index between 18.0-32.0 kg/m square, capped weight at 120kg, for HVs (Parts A, B, and E); body mass index between 16.0-35.0 kg/m square, capped weight at 125kg for patients (Parts C, D, F, and G)
- •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
- •Adequate contraception use (for men and women of childbearing potential)
- •No clinically significant abnormalities or history of relevant diseases
- •Key Inclusion Criteria (Part C and F only)
- •Documented history of COPD with a post-bronchodilator Forced Expiratory Volume in 1 second/Forced Vital Capacity less than 0.70
- •Key Inclusion Criteria (Parts D and G)
- •1. Participants with confirmed diagnosis of CRSwNP
排除标准
- •for (Parts A, B, C, D, E, F, and G)
- •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 (Part C and F only)
- •Current diagnosis of other significant pulmonary disease
- •Significant or unstable cardiovascular diseases
- •Recent clinically significant infection
- •Inability to perform spirometry
- •Key Exclusion Criteria (Parts D and G)
- •Steroid refractoriness: Refractory to systemic corticosteriods for CRSwNP
- •Sinonasal surgery (recent/extensiv)
- •Consitions interfering with nasal assessments
- •Excluded sinonasal/systemic diseases
结局指标
主要结局
Number of participants with change in Laboratory assessments
时间窗: Part A- Up to Day 141; Part B and C- Up to Day 169 post first dose administration
Laboratory assessments include hematology, coagulation, clinical chemistry and urinalysis
Number of participants with change in vital sign measurements following dose administration.
时间窗: Part A- Up to Day 141; Part B and C- Up to Day 169 post first dose administration
Blood pressure and heart rate will be assessed.
Number of participants with change in physical examination following dose administration.
时间窗: Part A- Up to Day 141; Part B and C- Up to Day 169 post first dose administration
Physical examination will be assessed.
Number of participants with change in 12-lead ECG readings
时间窗: Part A- Up to Day 141; Part B and C- Up to Day 169 post first dose administration
12-lead ECG will be assessed.
Number of participants with adverse events following single and multiple administration of BBT002
时间窗: Parts A and E - up to 141 days post first dose administration; Parts B, C, D, F, and G - up to 169 days post first dose administration
Incidence, relatedness, and severity of adverse events (AEs) graded per CTCAE v6.0.
Number of participants with change in Laboratory assessments
时间窗: Parts A and E - up to 141 days post first dose administration; Parts B, C, D, F, and G - up to 169 days post first dose administration
Laboratory assessments include hematology, coagulation, clinical chemistry and urinalysis
Number of participants with change in vital sign measurements following dose administration.
时间窗: Parts A and E - up to 141 days post first dose administration; Parts B, C, D, F, and G - up to 169 days post first dose administration
Blood pressure and heart rate will be assessed.
Number of participants with change in physical examination following dose administration.
时间窗: Parts A and E - up to 141 days post first dose administration; Parts B, C, D, F, and G - up to 169 days post first dose administration
Physical examination will be assessed.
Number of participants with change in 12-lead ECG readings
时间窗: Parts A and E - up to 141 days post first dose administration; Parts B, C, D, F, and G - up to 169 days post first dose administration
12-lead ECG will be assessed.
Number of participants with adverse events following single and multiple administration of BBT002
时间窗: Part A- Up to Day 141; Part B and C- Up to Day 169 post first dose administration
Incidence, relatedness, and severity of adverse events (AEs) graded per CTCAE v5.0.
次要结局
- 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- Area under the curve (AUC)(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)
- PK parameters- Time of maximum observed Concentration (Tmax)(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)