A Randomized, Blinded, Placebo-controlled, Single- and Multiple-ascending Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, Immunogenicity, Pharmacodynamics and Clinical Activity of BBT001 in HVs and AD Patient
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 99
- 试验地点
- 10
- 主要终点
- Number of participants with adverse events following single and multiple administration of BBT001
研究概览
简要总结
This is a Phase 1, randomized, blinded, placebo controlled, single ascending dose (SAD) study of BBT001 in healthy volunteers (HVs) and adult patients with moderate to severe Atopic Dermatitis (AD).
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 (seven repeated doses in patients with moderate to severe AD, multiple ascending Dose in patients part)
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •( Part A and B):
- •Age of 18-65 years.
- •Body mass index between 18-28 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.
- •Adequate contraception use (for men and women of childbearing potential).
- •No clinically significant abnormalities or history of relevant diseases.
- •Key Inclusion Criteria (Part B only):
- •Must have dermatologist-confirmed chronic atopic dermatitis (≥12 months). Inadequate response to topical treatments or where they are medically inadvisable.
- •Moderate to severe atopic dermatitis
- •Validated investigator's global assessment for atopic dermatitis (vIGA-ADTM) score ≥3
- •Atopic lesions cover ≥10% of body surface area (BSA)
- •Average peak pruritus numeric rating scale (PP-NRS) score ≥4 in the 7 days before randomization.
- •Eczema Area and Severity Index (EASI) score ≥16 at screening and randomization visits.
- •（for biologic/JAKi experienced subjects) Patients with prior systemic exposure to the following agents are eligible for enrollment: biologics targeting IL-4/IL-13 or IL-31 pathway or JAK inhibitors.
排除标准
- •for (Part A&B)
- •Significant health issues, such as: diabetes, positive tests for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B surface antigen (HBsAg), 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 issues, or abnormal kidney function.
- •Positive drug/alcohol tests or abnormal vital signs at screening or Day -
- •Abnormal Electrocardiogram (ECG) findings
- •History of drug/alcohol abuse in the past 2 years.
- •Donated >500mL blood within 2 months of screening.
- •History of severe allergic reactions or hypersensitivity.
- •Key Exclusion Criteria for (Part B only)
- •Skin diseases other than atopic dermatitis, significant tattoos, or scarring.
- •Receipt of immunoglobulin or blood products within 30 days.
- •Atopic dermatitis with ocular symptoms or chronic ocular steroid use.
- •Chronic pruritus from conditions other than atopic dermatitis.
- •Acute/treated infections or chronic skin infections.
- •Current use of sedating antihistamines or corticosteroids.
研究组 & 干预措施
Part A- Placebo(Single Ascending Dose)
A single dose of Placebo will be administered in healthy volunteers
干预措施: Placebo (Drug)
Part B -Placebo (Multiple Ascending Dose))
Seven repeat doses of Placebo will be administered in patients with moderate to severe atopic dermatitis
干预措施: Placebo (Drug)
Part B- BBT001(Multiple Ascending Dose)
Seven repeat doses of BBT001 will be administered in patients with moderate to severe atopic dermatitis
干预措施: BBT001 (Drug)
Part A -BBT001(Single Ascending Dose)
A single dose of BBT001 will be administered in healthy volunteers
干预措施: BBT001 (Drug)
结局指标
主要结局
Number of participants with adverse events following single and multiple administration of BBT001
时间窗: Part A- Up to Day 141; Part B - Up to Day 169 post first dose administration
Incidence, relatedness, and severity of adverse events graded per NCI CTCAE v5.0.
Number of participants with change in vital sign measurements following treatment administration.
时间窗: Part A- Up to Day 141; Part B-Up to Day 169 post first dose administration
Blood pressure and heart rate will be assessed.
Number of participants with change in serum blood parameters.
时间窗: Part A- Up to Day 141; Part B - Up to Day 169 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: 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 12-lead electrocardiogram (ECG) results measurements following treatment administration.
时间窗: Part A- Up to Day 141; Part B - Up to Day 169 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- maximum observed Concentration (Cmax)(At specified timepoints pre-dose and up to 169 days post first dose administration.)
- Pharmacokinetics parameters- Total clearance (CL)(At specified timepoints pre-dose and up to 169 days post first dose administration)
- Pharmacokinetics parameters- - Elimination Half-life (t1/2).(At specified timepoints pre-dose and up to 169 days post first dose administration)
- Pharmacokinetics parameters- Area under the curve (AUC)(At specified timepoints pre-dose and up to 169 days post first dose administration)
- Pharmacokinetics parameters- Time for maximum observed Concentration (Tmax)(At specified timepoints pre-dose and up to 169 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 169 days post first dose administration)
- Pharmacokinetics parameters- Volume of distribution (Vz)(At specified timepoints pre-dose and up to 169 days post first dose administration)