A Phase I Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD3152 in Healthy Japanese Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- To evaluate the safety and tolerability of AZD3152 - AEs
研究概览
简要总结
AZD3152 is being evaluated for administration to prevent COVID-19. This Phase I study will gather important information on the safety and tolerability of AZD3152 as well as relevant data on the PK, PD (as the neutralising responses against SARS-CoV-2) profile and the generation of ADA to AZD3152.
详细描述
This is a Phase I, randomised, double-blind, placebo controlled study evaluating the safety, tolerability, PK and PD of AZD3152 in healthy Japanese adult participants, 18 to 55 years of age. Approximately 24 healthy participants will be randomised at up to 2 study sites.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Japanese men and women and 18 to 55 years of age inclusive, at the time of signing the informed consent.
- •No positive results of SARS-CoV-2 NAT and/or rapid antigen tests.
- •Healthy participants by medical history, physical examination, baseline safety laboratory studies, and screening parameters, according to the judgement of the investigators, with no concomitant disease or concomitant medication.
- •ECG without clinically significant abnormalities.
- •Able to complete the Follow-up Period through Day 361 as required by the protocol.
- •Body weight ≥ 45 kg and ≤ 110 kg and BMI ≥ 18.0 to ≤ 30.0 kg/m2.
排除标准
- •Known hypersensitivity to any component of the IMP.
- •History of allergic disease or reactions likely to be exacerbated by any component of the IMP.
- •Previous hypersensitivity, infusion related reaction or severe adverse reaction following administration of mAbs.
- •Fever above 38.0°C on day prior to or on day of randomisation/dosing.
- •AST, ALT or serum creatinine above ULN; bilirubin and ALP >1.5 × ULN.
- •Any vaccination except for COVID-19 vaccine (e.g., inactivated influenzae vaccine) planned.
- •SARS CoV-2 or COVID-19:
- •Receipt of a COVID-19 vaccine within 3 months. COVID-19 infection within 3 months prior.
研究组 & 干预措施
Cohort 1 - AZD3152 300 mg IM direct anterolateral thigh injection
干预措施: AZD3152 (Cohort 1) (Biological)
Cohort 1 - Placebo IM direct anterolateral thigh injection
干预措施: Placebo (Cohort 1) (Biological)
Cohort 3 - Placebo IV administration
干预措施: Placebo (Cohort 3) (Biological)
Cohort 2 - AZD3152 600 mg IM direct anterolateral thigh injection
干预措施: AZD3152 (Cohort 2) (Biological)
Cohort 2 - Placebo direct anterolateral thigh injection
干预措施: Placebo (Cohort 2) (Biological)
Cohort 3 - AZD3152 1200 mg IV administration
干预措施: AZD3152 (Cohort 3) (Biological)
结局指标
主要结局
To evaluate the safety and tolerability of AZD3152 - AEs
时间窗: Up to Visit 9 (Day 91)
Occurrence of AEs collected up to Visit 9 (Day 91)
To evaluate the safety and tolerability of AZD3152 - SAEs, MAAEs, and AESIs
时间窗: Up to Visit 12 (Day 361)
Occurrence of SAEs, MAAEs, and AESIs collected up to Visit 12 (Day 361)
To evaluate the safety and tolerability of AZD3152 - Blood pressure
时间窗: Up to Visit 7 (Day 29)
The following variables will be collected: * Systolic Blood pressure * Diastolic Blood pressure
To evaluate the safety and tolerability of AZD3152 - Pulse rate
时间窗: Up to Visit 7 (Day 29)
Pulse rate will be collected
To evaluate the safety and tolerability of AZD3152 - Axillary temperature
时间窗: Up to Visit 7 (Day 29)
Axillary temperature will be collected
To characterise the Serum Pharmacokinetics of AZD3152 - Maximum concentration (Cmax)
时间窗: Up to Visit 12 (Day 361)
AZD3152 concentration over time and Pharmacokinetics parameters
To characterise the Serum Pharmacokinetics of AZD3152 - Time to maximum concentration (tmax)
时间窗: Up to Visit 12 (Day 361)
AZD3152 concentration over time and Pharmacokinetics parameters
To evaluate the safety and tolerability of AZD3152 - Respiratory rate
时间窗: Up to Visit 7 (Day 29)
Respiratory rate will be collected
To evaluate the safety and tolerability of AZD3152 - Heart rate
时间窗: Up to Visit 7 (Day 29)
Heart rate will be recorded
To evaluate the safety and tolerability of AZD3152 - PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval
时间窗: Up to Visit 7 (Day 29)
PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval will be recorded
To characterise the Serum Pharmacokinetics of AZD3152 - Concentration at the end of infusion (Ceoi) (after intravenous only)
时间窗: Up to Visit 12 (Day 361)
AZD3152 concentration over time and Pharmacokinetics parameters
To characterise the Serum Pharmacokinetics of AZD3152 - Terminal half-life (t½)
时间窗: Up to Visit 12 (Day 361)
AZD3152 concentration over time and Pharmacokinetics parameters
To characterise the Serum Pharmacokinetics of AZD3152 - Area under the concentration-time curve at the last measured time point (AUClast)
时间窗: Up to Visit 12 (Day 361)
AZD3152 concentration over time and Pharmacokinetics parameters
To characterise the Serum Pharmacokinetics of AZD3152 - Area under the concentration-time curve from time zero extrapolated to infinity (AUCinf)
时间窗: Up to Visit 12 (Day 361)
AZD3152 concentration over time and Pharmacokinetics parameters
To evaluate the safety and tolerability of AZD3152 - Haematology - White blood cell count
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - White blood cell count
To evaluate the safety and tolerability of AZD3152 - Haematology - Red blood cell count
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Red blood cell count
To evaluate the safety and tolerability of AZD3152 - Haematology - Haemoglobin
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Haemoglobin
To evaluate the safety and tolerability of AZD3152 - Haematology - Haematocrit
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Haematocrit
To evaluate the safety and tolerability of AZD3152 - Haematology - Mean corpuscular volume
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Mean corpuscular volume
To evaluate the safety and tolerability of AZD3152 - Haematology - Neutrophils absolute count
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Neutrophils absolute count
To evaluate the safety and tolerability of AZD3152 - Haematology - Mean corpuscular haemoglobin
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Mean corpuscular haemoglobin
To evaluate the safety and tolerability of AZD3152 - Haematology - Mean corpuscular haemoglobin concentration
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Mean corpuscular haemoglobin concentration
To evaluate the safety and tolerability of AZD3152 - Haematology - Lymphocytes absolute count
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Lymphocytes absolute count
To evaluate the safety and tolerability of AZD3152 - Haematology - Monocytes absolute count
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Monocytes absolute count
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Potassium
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Potassium
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Glucose
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Glucose
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - C reactive protein
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - C reactive protein
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Gamma glutamyl transpeptidase
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Gamma glutamyl transpeptidase
To evaluate the safety and tolerability of AZD3152 - Urinalysis - Blood
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Blood
To evaluate the safety and tolerability of AZD3152 - Urinalysis - Microscopy
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Microscopy
To evaluate the safety and tolerability of AZD3152 - Urinalysis - Protein
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Protein
To evaluate the safety and tolerability of AZD3152 - Haematology - Eosinophils absolute count
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Eosinophils absolute count
To evaluate the safety and tolerability of AZD3152 - Haematology - Basophils absolute count
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Basophils absolute count
To evaluate the safety and tolerability of AZD3152 - Haematology - Reticulocytes absolute count
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Reticulocytes absolute count
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Sodium
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Sodium
To evaluate the safety and tolerability of AZD3152 - Haematology - Platelets
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Platelets
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Blood urea nitrogen
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Blood urea nitrogen
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Creatinine and estimated glomerular filtration rate
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Creatinine and estimated glomerular filtration rate
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Albumin
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Albumin
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Calcium
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Calcium
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Phosphate
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Phosphate
To evaluate the safety and tolerability of AZD3152 - Alkaline phosphatase
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Alkaline phosphatase
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Alanine aminotransferase
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Alanine aminotransferase
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Unconjugated bilirubin
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Unconjugated bilirubin
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Conjugated bilirubin
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Conjugated bilirubin
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Creatine kinase
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Creatine kinase
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Aspartate aminotransferase
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Aspartate aminotransferase
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Total bilirubin
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Total bilirubin
To evaluate the safety and tolerability of AZD3152 - Coagulation - Activated partial thrombin time
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Activated partial thrombin time
To evaluate the safety and tolerability of AZD3152 - Coagulation - Prothrombin time
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Prothrombin time
To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Troponin T and I
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Troponin T and I
To evaluate the safety and tolerability of AZD3152 - Urinalysis - Glucose
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - Glucose
To evaluate the safety and tolerability of AZD3152 - Coagulation - International normalised ratio
时间窗: Up to Visit 7 (Day 29)
The following will be collected: - International normalised ratio
次要结局
- The serum neutralising responses against SARS-CoV-2 using geometric mean titer (GMT) and geometric mean fold rise (GMFR) from baseline(Up to Visit 12 (Day 361))
- To evaluate the Anti-Drug Antibody responses to AZD3152 in serum(Up to Visit 12 (Day 361))