A Randomized, Double-blind, Single-dose, Three-arm, Parallel-group, Phase 1 Study to Compare Pharmacokinetic and Safety of TRS003 to China-approved Bevacizumab and US-licensed Avastin®，When Administered to Healthy Male Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 114
- 试验地点
- 2
- 主要终点
- AUC0-inf，Area Under the Serum Concentration Versus Time Curve，Time 0 to Infinity
研究概览
简要总结
This is a 12-week, randomized, double-blind, single-dose pharmacokinetic (PK) study. Approximately 114 healthy male participants (screening occurred within 28 days prior to dosing) will be randomized 1:1:1 to either TRS003, China-approved bevacizumab, and US-licensed Avastin® groups. Study drug will be dispensed as a single 3 mg/kg dose for intravenous infusion within 90 minutes. PK and immunogenicity samples will be collected and safety will be assessed. The primary objective of this study was to demonstrate pharmacokinetic similarity between TRS003, China-approved bevacizumab and US-licensed Avastin®, as measured by AUC0-inf in healthy male participants after a single 3 mg/kg dose.
详细描述
The primary assessment of PK similarity will be based upon a 90 percentage confidence interval (CI) for the ratio of the geometric means (TRS003, China-approved bevacizumab and US-licensed Avastin®) for AUC0-inf on PK analysis set. If the 90 percentage CI of the ratio of the geometric means for AUC0-inf is within the range of 80-125 percentage, then PK similarity will be concluded. Secondary PK parameters such as but not limited to Cmax, AUClast will be analyzed using the same statistical approach. A nonparametric approach, for example, Wilcoxon signed-rank test, will be taken to evaluate parameters such as t1/2. Exploratory analyses may be performed for other PK parameters as deemed appropriate. All adverse events (AEs) will be listed and summarized using descriptive methodology. The incidence of AEs for each treatment will be presented by severity and association with the study drugs. Clinical laboratory parameters, vital signs, and electrocardiogram (ECG) parameters will be listed and summarized using descriptive statistics. The number and percentage of participants testing positive for anti-drug antibodies (ADAs) will be summarized by treatment and time point.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
盲法说明
double-blind
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy, male participants, 18-55 years old with no significant medical history, and in good health as determined by detailed medical history, full physical examination, vital signs, 12-lead electrocardiogram (ECG), urinalysis and laboratory tests at screening.
- •Body mass index of 17.5-30.5 kg/m^2 and body weight of 50-95 kg.
- •Protocol-specified hematology, coagulation, blood chemistry and urinalysis within the laboratory normal range at screening, unless deemed not clinically significant by the Investigator.
- •Participants must have adequate organ function according to the following laboratory values:
- •Bone marrow function (absolute neutrophil count ≥1500/mm^3 and platelet count ≥100,000/mm^3)
- •Adequate liver function [alanine aminotransferase (ALT) ≤3 × upper limit normal (ULN) and alkaline phosphatase ≤2 × ULN, total bilirubin ≤1.5 mg/dL]
- •Adequate renal function creatinine clearance ≥60 mL/min based on Cockcroft-Gault equation
- •Participants must agree to use an acceptable form of birth control throughout the study and for at least 18 weeks after the study is over.
排除标准
- •Participants unable to give voluntary informed consent.
- •Evidence or history of clinically significant disease, cancer other than adequately treated basal cell or squamous cell carcinoma of the skin.
- •Participants on anticoagulant drugs, anemic or with known bleeding diatheses.
- •Participants with a history of severe, uncontrolled hypertension, heart disease, cerebrovascular incidents, gastrointestinal bleeding, hemoptysis, frequent epistaxis or gingival bleeding.
- •History clinically significant orthostatic hypotension, fainting spells, vasovagal syncope.
- •Uncontrolled severe hypertension (140/90 mm Hg).
- •Previous treatment with an anti-VEGF antibody or any other antibody or protein targeting the VEGF receptor.
- •Use of any prescription, investigational drugs, herbal supplements or nonprescription drugs within 1 month or 5 half-lives (whichever is longer) prior to the first dose, or dietary supplements within 1 week prior to the first dose. If needed, paracetamol/acetaminophen may be used, but must be documented in the Concomitant medications/Significant non-drug therapies page of the case report form (CRF).
- •Serious unhealed wound, cutaneous ulcer or bone fracture at the time of screening.
- •Major surgery or major dental procedure or significant traumatic injury within 2 months prior to screening, or any planned surgery or procedure within 3 months after investigational treatment administration. Participants must have recovered from all acute surgery- or trauma-related complications.
- •Participant's medical and family history of recent or recurrent thromboembolism or other clotting and coagulation disorders.
- •Donated blood over 400 mL within 3 months.
- •History of relevant and clinically significant intra-abdominal inflammation, gastrointestinal perforation or gall bladder perforation.
- •History of severe allergic or anaphylactic reaction to a therapeutic drug or severe seasonal allergies.
- •Recent (within the last three [3] years) and/or recurrent history of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).
- •A positive hepatitis B, hepatitis C or HIV tests at screening indicative of a current or past infection.
- •Current use of tobacco or nicotine-containing products. Concomitant treatment was given only if Investigator believes strictly necessary and should be documented.
- •Current use of any biologic drugs.
结局指标
主要结局
AUC0-inf，Area Under the Serum Concentration Versus Time Curve，Time 0 to Infinity
时间窗: Pre-dose, 0 hour (End of infusion, EOI), 0.5 hour, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours, 336 hours, 672 hours, 1008 hours, 1344 hours, 1680 hours, and 2016 hours post EOI
The primary assessment of PK similarity will be based upon a 90 percentage CI for the ratio of the geometric means (TRS003, China-approved bevacizumab and US-licensed Avastin®) for AUC0-inf on PK analysis set. If the 90 percentage CI of the ratio of the geometric means for AUC0-inf is within the range of 80-125 percentage, then PK similarity will be concluded.
次要结局
- Number of Participants Who Develop Detectable Anti-drug Antibody (ADA)(Pre-dose, 336 hours, 672 hours, 1344 hours and 2016 hours after EOI (End of infusion))
- Cmax, Maximum Drug Concentration(Pre-dose, 0 hour (End of infusion, EOI), 0.5 hour, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours, 336 hours, 672 hours, 1008 hours, 1344 hours, 1680 hours, and 2016 hours post EOI)
- Number of Participants With Adverse Events (AEs)(Within 85 days following the drug administration)
- AUC0-last, Area Under the Serum Concentration-time Curve，Time 0 to Last(Pre-dose, 0 hour (End of infusion, EOI), 0.5 hour, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours, 336 hours, 672 hours, 1008 hours, 1344 hours, 1680 hours, and 2016 hours post EOI)