A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of APNmAb005 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Number of subjects with Adverse Events (AEs)
研究概览
简要总结
This is a Phase 1, first-in-human (FIH), double-blinded, placebo-controlled study where healthy subjects are randomly allocated to receive APNmAb005 or placebo. Approximately 5 dosing groups (cohorts) are planned with 8 subjects (randomized to 6 active: 2 placebo) per cohort. the starting dose of APNmAb005 is 5 mg/kg and the anticipated doses for subsequent cohorts are 10, 25, 50 and 70 mg/kg. A Safety Review Team (SRT) will review data on an ongoing basis throughout the study and before progression to the next dose level cohort.
Subjects will receive a single dose of either APNmAb005 or placebo administered as a single IV infusion on Day 1 of the study and will remain in the study center until Day 3 (48 hours after dosing). They will return to the study center for 7 outpatient visits. The duration of the study, excluding screening, is approximately 71 days.
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
- Quadruple (Participant, Care Provider, 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
- •Body Mass Index (BMI) of 18.5 to 32 kg/m² inclusive, at screening.
- •Female subjects of childbearing potential must use an acceptable method of birth control from screening until at least 90 days after study drug dosing; OR be surgically sterile; OR be postmenopausal. All female subjects must have a negative pregnancy test at screening and before the first dose of the study drug. Female subjects must also agree to refrain from egg donation during the study and for at least 90 days after study drug dosing.
- •Male subjects must agree to use a condom when sexually active with a female partner of childbearing potential during the study and for at least 90 days after study drug dosing (or be surgically sterile); OR agree to practice abstinence during the study and for at least 90 days after study drug dosing. Male subjects must also agree to refrain from sperm donation during the study and for at least 90 days after study drug dosing.
- •Agree to comply with all protocol requirements.
- •Provide written informed consent.
排除标准
- •Unable or unwilling to undergo venipuncture or tolerate venous access, or is unable or unwilling to undergo lumbar puncture.
- •Has any significant acute or chronic medical illness that would impact the subject's ability to complete all study requirements or impact assessment of study data; or subject as had a clinically significant illness within 30 days prior to study drug dosing.
- •Any medical condition or documented history that is a contraindication to lumbar puncture (e.g. bleeding disorder, spinal deformity).
- •Positive COVID-19 molecular diagnostic test result at screening or prior to study drug dosing; or subject has known or suspected consequence from prior COVID-19 infection.
- •History of cardiac, endocrine, gastrointestinal, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal or oncogenic (with the exception of resected skin basal cell carcinoma) disease within 5 years prior to screening).
- •NOTE: Subjects with treated stable psychiatric conditions (e.g. anxiety, depression) are not allowed.
- •Clinically significant neurological or psychiatric disorder.
- •Major surgery, as determined by investigator, within 4 weeks prior to study drug dosing.
- •Systolic blood pressure >140 mm Hg and/or diastolic blood pressure >90 mm Hg.
- •Received any vaccine or used any prescription or over-the-counter medications (except paracetamol [up to 2 g per day]), including herbal or nutritional supplements, within 14 days prior to study drug dosing.
- •Consumed caffeine- or xanthine-containing products within 48 hours prior to study drug dosing.
- •Subject is a smoker or has regularly used nicotine or nicotine-containing products (e.g. snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) within 3 months prior to study drug dosing.
- •Subject is involved in vigorous or strenuous physical activity or contact sports within 24 hours prior to study drug dosing.
- •Subject has donated blood or blood products >450 mL within 3 months prior to study drug dosing.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
APNmAb005 (50 mg/kg) vs Placebo
Single Ascending Dose (SAD)
干预措施: APNmAb005 (Drug)
APNmAb005 (5mg/kg) vs Placebo
Single Ascending Dose (SAD)
干预措施: APNmAb005 (Drug)
APNmAb005 (5mg/kg) vs Placebo
Single Ascending Dose (SAD)
干预措施: Placebo (Drug)
APNmAb005 (10 mg/kg) vs Placebo
Single Ascending Dose (SAD)
干预措施: APNmAb005 (Drug)
APNmAb005 (10 mg/kg) vs Placebo
Single Ascending Dose (SAD)
干预措施: Placebo (Drug)
APNmAb005 (25 mg/kg) vs Placebo
Single Ascending Dose (SAD)
干预措施: APNmAb005 (Drug)
APNmAb005 (25 mg/kg) vs Placebo
Single Ascending Dose (SAD)
干预措施: Placebo (Drug)
APNmAb005 (50 mg/kg) vs Placebo
Single Ascending Dose (SAD)
干预措施: Placebo (Drug)
APNmAb005 (70 mg/kg) vs Placebo
Single Ascending Dose (SAD)
干预措施: APNmAb005 (Drug)
APNmAb005 (70 mg/kg) vs Placebo
Single Ascending Dose (SAD)
干预措施: Placebo (Drug)
结局指标
主要结局
Number of subjects with Adverse Events (AEs)
时间窗: Day 70
Defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Data collected by subject observations and data collected on AE page of electronic Case Report Form (eCRF), or other documents relevant to subject safety.
Number of subjects with Treatment-emergent AEs (TEAEs)
时间窗: Day 70
Defined as any event not present before exposure to study drug or any event already present that worsens in intensity or frequency after exposure. Data collected by subject observations and data collected on AE page of electronic Case Report Form (eCRF), or other documents relevant to subject safety.
Number of subjects with Serious Adverse Events (SAEs)
时间窗: Day 70
Defined as any AE for which there is a reasonable possibility that the study drug caused the AE. Data collected by subject observations and data collected on AE page of electronic Case Report Form (eCRF), or other documents relevant to subject safety.
Number of subjects with AEs resulting in Study Discontinuation
时间窗: Day 70
Data collected by subject observations and data collected on AE page of electronic Case Report Form (eCRF), or other documents relevant to subject safety.
Number of participants with Vital Sign Abnormalities
时间窗: Day 70
Measured by systolic and diastolic blood pressures, pulse rate, respiratory rate and body temperature.
Number of participants with Electrocardiogram (ECG) Abnormalities
时间窗: Day 70
Measured by 12-lead ECG
Number of participants with Clinical Laboratory Abnormalities
时间窗: Day 70
Measured by hematology, coagulation, serum chemistry and urinalysis.
次要结局
- Cmax of APNmAb005 in blood(Thru Day 70)
- Cmax of APNmAb005 in CSF(Thru Day 14)
- Mean Total tau concentration in plasma(Thru Day 70)
- Mean change in Total tau concentration in plasma(Baseline and Day 70)
- Mean Total tau concentration in CSF(Thru Day 14)
- Mean change in Total tau concentration in CSF(Baseline and Day 14)
- Mean p-tau 181 concentration in plasma(Thru Day 70)
- Mean change in p-tau 181 concentration in plasma(Baseline and Day 70)
- Mean p-tau 181 concentration in CSF(Thru Day 14)
- t1/2 of APNmAb005 in plasma(Thru Day 70)
- t1/2 of APNmAb005 in CSF(Thru Day 14)
- Number of participants with ADA formation against APNmAb005(Thru Day 70)
- Number of participants with no ADA formation against APNmAb005(Thru Day 70)
- AUC0-t of APNmAb005 in plasma(Thru Day 70)
- AUC0-t of APNmAb005 in CSF(Thru Day 14)
- CL of APNmAb005 in blood.(Thru Day 70)
- Vd of APNmAb005 in CSF(Thru Day 14)
- Tmax of APNmAb005 in blood(Thru Day 70)
- Tmax of APNmAb005 in CSF(Thru Day 14)
- CL of APNmAb005 in CSF(Thru Day 14)
- Vd of APNmAb005 in plasma(Thru Day 70)
- Mean change in p-tau 181 concentration in CSF(Baseline and Day 14)
- Mean p-tau 217 concentration in plasma(Thru Day 70)
- Mean change in p-tau 217 concentration in plasma(Baseline and Day 70)
- Mean p-tau 217 concentration in CSF(Thru Day 14)
- Mean change in p-tau 217 concentration in CSF(Baseline and Day 14)
- Mean p-tau 231 concentration in plasma(Thru Day 70)
- Mean change in p-tau 231 concentration in plasma(Baseline and Day 70)
- Mean p-tau 231 concentration in CSF(Thru Day 14)
- Mean change in p-tau 231 concentration in CSF(Baseline and Day 14)