NCT04238650已完成1 期
A Randomised, Double Blind, Two-Arm, Single Dose, Parallel Phase I Study To Compare the Pharmacokinetics, Safety and Immunogenicity of MB02 (a Proposed Bevacizumab Biosimilar Drug) and EU Approved Avastin® in Japanese Healthy Male Volunteers
mAbxience Research S.L.1 个研究点 分布在 1 个国家目标入组 49 人开始时间: 2019年8月2日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Area Under the Serum Concentration-time Curve From Time Zero to Infinity [AUC(0-∞)]
研究概览
简要总结
A Randomised, Double Blind, Two-Arm, Single Dose, Parallel Phase I Study To Compare the Pharmacokinetics, Safety and Immunogenicity of MB02 (a Proposed Bevacizumab Biosimilar Drug) and EU Approved Avastin® in Japanese Healthy Male Volunteers.
During the course of the study, the similarity in pharmacokinetics will be assessed by sampling the levels of drug in the blood, and by comparing these levels among the different administration arms. Safety, tolerability, and immunologic response to the administered drugs will also be evaluated throughout.
详细描述
The primary PK parameter endpoint is AUC(0-∞) for bevacizumab. The secondary PK endpoints will include all other PK parameters for bevacizumab, including Cmax, tmax, t1/2, CL and AUClast.
The serum PK parameters of bevacizumab will be calculated using standard noncompartmental methods. An analysis of covariance model will be used to analyse the log-transformed primary PK parameters (AUC[0-∞] and Cmax) and AUClast. The model will include a fixed effect for treatment and body weight as a covariate.
All other PK parameters will not be subject to inferential statistical analysis.
Estimates of geometric mean ratios together with the corresponding 90% confidence intervals (CI) will be derived for the comparisons of the PK parameters as follows:
• MB02 versus EU Avastin®
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 20 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions. Subjects must have signed an informed consent before any study-related procedure or evaluation is performed.
- •Healthy Japanese males aged ≥20 to ≤55 years, inclusive, at Screening.
- •Subjects with Body mass index (BMI) between ≥18.5 to ≤28 kg/m2 and total body weight between ≥50 and ≤100 kg, at Screening
- •Subject must have no clinically relevant abnormalities identified by a detailed medical history.
- •Systolic blood pressure ≤140 mm Hg and diastolic blood pressure ≤90 mm Hg.
- •Computerized (12-lead) electrocardiogram (ECG) recording without signs of clinically relevant pathology.
- •All other values for hematology, coagulation and for biochemistry and urinalysis tests of blood and urine within the normal range or showing no clinically relevant deviations as judged by the Investigator, according to the following laboratory values:
- •Adequate bone marrow function
- •Absolute neutrophil count ≥1.5 × 109 L
- •Platelet count ≥100 × 109 L
- •Hemoglobin >10 g/dl
- •Adequate liver function:
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ ULN
- •Alkaline phosphatase (ALP) ≤1.5 × ULN
- •Total bilirubin <1.5 × ULN
- •Serum albumin: >3.5 g/dL
- •Low density lipoprotein cholesterol ≤139 mg/dL
- •High density lipoprotein cholesterol ≥ 40 mg/dL
- •Creatine kinase (CK) <2 ULN at D-1
- •Adequate coagulation:
- •International normalised ratio (INR) 0.8 to 1.3
- •Adequate renal function:
- •Blood urea nitrogen: ≤1.5 × ULN
- •Creatinine: <1.5 mg/dL
- •Urine dipstick for proteinuria <2+.
- •All intermittent medications should have been stopped at least 30 days prior to admission to the clinical research center.
- •Subjects agree to use contraception.
- •Ability and willingness to abstain from alcoholic beverages (alcohol) 48 hours prior to admission to the clinical research center.
排除标准
- •History of relevant allergy/hypersensitivity (including allergy to drug or its excipients).
- •Previous treatment with an anti VEGF antibody like bevacizumab or any other protein or antibody targeting the VEGF receptor.
- •History of bleeding disorders or protein C, protein S, and/or factor V Leiden deficiency.
- •Known history of clinically significant essential hypertension (subjects under any antihypertensive treatment included), orthostatic hypotension, fainting spells or blackouts for any reason, cardiac failure or history of thromboembolic conditions.
- •History of GI perforation, ulcers, gastro oesophageal reflux, inflammatory bowel disease, diverticular disease, diverticular disease, any fistulae, pulmonary hemorrhage (hemoptysis) or reversible posterior leukoencephalopathy syndrome.
- •Any out-of-range laboratory values considered clinically significant by the investigator.
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
- •Any current or recent history of active infections, including localized infections. (Within 2 months prior Screening Visit for any serious infection which requires hospitalization or intravenous anti-infective, and within 14 days prior Screening Visit for any active infection which requires oral treatment). A negative result for human immunodeficiency virus (HIV), Hepatitis B (Hep B), and hepatitis C (Hep C) is required for participation. If subject shows positive Hepatitis B test, but results are compatible with prior immunisation and not infection may be included at the discretion of the Investigator.
- •Clinically relevant history of alcoholism, addiction or drug/chemical abuse prior to Check-in, and/or positive urinary drug test screen and/or positive breath alcohol test at Screening or Check in. Average intake of more than 24 units of alcohol / wk. (1 unit of alcohol equals ~250mL of beer, 100mL of wine or 35mL of spirits). Positive urine drug screen (opiates, methadone, cocaine, amphetamines (including ecstasy or methamphetamines), cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants and phencyclidine).
- •Treatment with non-topical medications within 7 days prior to study drug administration, with the exception of hormonal contraceptives, multivitamins, vitamin C, food supplements and a limited amount of acetaminophen, which may be used throughout the study.
- •Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 60 days prior to Check-in, or within 5 half lives of the investigational drug used in the study.
- •Subjects considered unsuitable for inclusion by the investigator (e.g., inability to understand and comply with the study requirements or presence of any condition which, in the opinion of the investigator, would not allow safe participation in the study).
- •Strenuous exercise within seven days prior to admission to the clinical research center.
- •Significant or acute illness within 15 days prior to drug administration that may impact safety assessments per the judgement of the investigator.
- •Unsuitable veins for infusion and/or venepuncture.
- •History of, or planned surgery, including suturing, dental surgery or wound dehiscence within 30 days of dosing, or within 30 days of the last study visit. Presence of a nonhealing wound or fracture.
- •Medically significant dental disease or dental neglect with signs and or symptoms of local or systemic infection that would likely require a dental procedure during the course of the study.
- •Use or intend to use slow-release medications/products considered to still be active within 30 days prior to Check-in, unless deemed acceptable by the Investigator (or designee).
- •Have received a live or attenuated vaccine from 3 months prior to Screening or have the intention to receive a vaccine during the study.
- •Intend to travel to a region where a vaccination will be required due to endemic disease within 3 months of dosing.
- •Use of tobacco- or nicotine-containing products within 1 year prior to Check-in, or positive cotinine test upon Screening or Check-in.
- •Receipt of blood products within 60 days prior to Check-in.
- •Person who performed blood sampling more than 400 mL within 90 days before administration of investigational drug, more than 200 mL blood within 30 days, or blood donation of blood plasma / platelet component within 14 days.
- •History of abnormal peripheral sensation including paraesthesia and/or numbness in arms and/or legs.
- •Have previously received Bevacizumab either under present study or under any other circumstances.
研究组 & 干预措施
MB02 (Bevacizumab Biosimilar)
Experimental
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
干预措施: MB02 (Bevacizumab Biosimilar) (Drug)
EU approved Avastin®
Active Comparator
Intervention Description: Sterile vial 400mg/16ml, single-dose 3mg/kg administered as 90-minute infusion on day 1.
干预措施: EU approved Avastin® (Drug)
结局指标
主要结局
Area Under the Serum Concentration-time Curve From Time Zero to Infinity [AUC(0-∞)]
时间窗: Predose, end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 38, Day 50, Day 62, and Day 70.
To compare the pharmacokinetic (PK) profiles of MB02 and EU Avastin® (in terms of AUC(0-∞)\]) in Japanese population to establish bioequivalence between the 2 study drugs.
次要结局
- Maximum Observed Serum Concentration (Cmax)(Predose, end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 38, Day 50, Day 62, and Day 70.)
- Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Observable Concentration (AUClast)(Predose, end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 38, Day 50, Day 62, and Day 70.)
- Incidence of Treatment-related Adverse Events (Safety)(Day 1 - Day 70)
- Incidence of ADA Including Nab (Immunogenicity)(Day -1, Day 14, 28, 50 and 70.)
- Time of Maximum Observed Serum Concentration (Tmax)(Predose, end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 38, Day 50, Day 62, and Day 70.)
- Apparent Serum Terminal Elimination Half Life (t1/2)(Predose, end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 38, Day 50, Day 62, and Day 70.)
- Total Body Clearance (CL)(Predose, end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 38, Day 50, Day 62, and Day 70.)
- Volume of Distribution (Vz)(Predose, end of infusion, 2, 3, 4, 5, 6, 8, 12, 24 h post-dose on Day 1-8, Day 10, Day 14, Day 21, Day 28, Day 38, Day 50, Day 62, and Day 70.)
研究者
研究点 (1)
Loading locations...
相似试验
已完成
1 期
Phase I Study to Compare the Pharmacokinetics, Pharmacodynamics, and Safety Between CT-P41 and US-licensed Prolia in Healthy Male SubjectsHealthy SubjectNCT06037395Celltrion154
进行中（未招募）
1 期
To Compare the Pharmacokinetics, Safety, and Immunogenicity of Subcutaneous CT-P6 and Herceptin in Healthy Male Subjects (Trastuzumab)HealthyNCT06687928Celltrion200
已完成
1 期
Biosimilar Study Comparing PK, PD, Safety and Immunogencity of BP11 With US Licensed Xolair and EU Approved XolairHealthy VolunteersNCT05053334Syneos Health165
Unknown
1 期
A Study to Evaluate LY01011 and Xgeva® in Healthy AdultsHealthy AdultsNCT04198636Luye Pharma Group Ltd.168
已完成
1 期
The Study of Omalizumab (CMAB007 and Xolair) in Healthy Subjects to Compare the PK, PD, Safety and ImmunogenicityHealthy VolunteersNCT05897008Taizhou Mabtech Pharmaceutical Co.,Ltd114