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Clinical study of safety, tolerance, and pharmacokinetics of nebulizer (INF-K + anti-inflammatory factor TFF2) in healthy volunteers and exploration of PK/PD fitting modeling in clinical trials of Novel Coronavirus Pneumonia (COVID-19) patients
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注册号:

Registration number:

ChiCTR2000035633 

最近更新日期:

Date of Last Refreshed on:

2020-08-30 

注册时间:

Date of Registration:

2020-08-15 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

雾化剂(INF-k +抑炎因子TFF2)联合应用在健康受试者中的安全性、耐受性和药代动力学的临床研究及探索新型冠状病毒肺炎(COVID-19)患者临床试验中PK/PD拟合建模研究 

Public title:

Clinical study of safety, tolerance, and pharmacokinetics of nebulizer (INF-K + anti-inflammatory factor TFF2) in healthy volunteers and exploration of PK/PD fitting modeling in clinical trials of Novel Coronavirus Pneumonia (COVID-19) patients 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

雾化剂(INF-k +抑炎因子TFF2)联合应用在健康受试者中的安全性、耐受性和药代动力学的临床研究及探索新型冠状病毒肺炎(COVID-19)患者临床试验中PK/PD拟合建模研究 

Scientific title:

Clinical study of safety, tolerance, and pharmacokinetics of nebulizer (INF-K + anti-inflammatory factor TFF2) in healthy volunteers and exploration of PK/PD fitting modeling in clinical trials of Novel Coronavirus Pneumonia (COVID-19) patients 

研究课题代号(代码):

Study subject ID:

 

在二级注册机构或其它机构的注册号:

The registration number of the Partner Registry or other register:

 

申请注册联系人:

刘艳 

研究负责人:

徐建青/刘艳 

Applicant:

Yan Liu 

Study leader:

Jianqing Xu/ Yan Liu 

申请注册联系人电话:

Applicant telephone:

+86 18616997883 

研究负责人电话:

Study leader's telephone:

+86 18616997883 

申请注册联系人传真 :

Applicant Fax:

 

研究负责人传真:

Study leader's fax:

 

申请注册联系人电子邮件:

Applicant E-mail:

liuyan@shphc.org.cn 

研究负责人电子邮件:

Study leader's E-mail:

liuyan@shphc.org.cn 

申请单位网址(自愿提供):

Applicant website(voluntary supply):

 

研究负责人网址(自愿提供):

Study leader's website(voluntary supply):

 

申请注册联系人通讯地址:

上海市金山区漕廊公路2901号 

研究负责人通讯地址:

上海市金山区漕廊公路2901号 

Applicant address:

2901 Caolang Road, Jinshan District, Shanghai, China 

Study leader's address:

2901 Caolang Road, Jinshan District, Shanghai, China 

申请注册联系人邮政编码:

Applicant postcode:

201508 

研究负责人邮政编码:

Study leader's postcode:

201508 

申请人所在单位:

上海市公共卫生临床中心 

Applicant's institution:

Shanghai Public Health Clinical Center 

是否获伦理委员会批准:

是 

Approved by ethic committee:

Yes 

伦理委员会批件文号:

Approved No. of ethic committee:

YJ-2020-S124-02 

伦理委员会批件附件:

Approved file of Ethical Committee:

查看附件View

批准本研究的伦理委员会名称:

上海市公共卫生临床中心医学伦理委员会 

Name of the ethic committee:

Shanghai Public Health Clinical Center Ethics Committee 

伦理委员会批准日期:

Date of approved by ethic committee:

2020-07-31 

伦理委员会联系人:

刘晓茜 

Contact Name of the ethic committee:

Xiaoqian Liu 

伦理委员会联系地址:

上海市金山区漕廊公路2901号 

Contact Address of the ethic committee:

2901 Caolang Road, Jinshan District, Shanghai, China 

伦理委员会联系人电话:

Contact phone of the ethic committee:

 

伦理委员会联系人邮箱:

Contact email of the ethic committee:

 

研究实施负责(组长)单位:

上海市公共卫生临床中心 

Primary sponsor:

Shanghai Public Health Clinical Center 

研究实施负责(组长)单位地址:

上海市金山区漕廊公路2901号 

Primary sponsor's address:

2901 Caolang Road, Jinshan District, Shanghai, China 

试验主办单位(项目批准或申办者):

Secondary sponsor:

国家:

中国

省(直辖市):

上海

市(区县):

Country:

China

Province:

Shanghai

City:

单位(医院):

上海市公共卫生临床中心

具体地址:

金山区漕廊公路2901号

Institution
hospital:

Shanghai Public Health Clinical Center

Address:

2901 Caolang Road, Jinshan District

经费或物资来源:

上海市公共卫生临床中心 

Source(s) of funding:

Shanghai Public Health Clinical Center 

研究疾病:

新型冠状病毒肺炎(COVID-19) 

Target disease:

Novel Coronavirus Pneumonia (COVID-19) 

研究疾病代码:

 

Target disease code:

 

研究类型:

干预性研究 

Study type:

Interventional study 

研究所处阶段:

探索性研究/预试验 

Study phase:

研究目的:

研究1 主要目的:雾化剂(IFN-κ+抑炎因子TFF2)联合应用单次给药在健康受试者中的安全性、耐受性。 次要目的:雾化剂(IFN-κ+抑炎因子TFF2)联合应用单次给药在健康受试者中的药代动力学。 研究2 检测前期研究者发起的临床研究“抗病毒药物+Ⅰ型IFN+抑炎因子TFF2联合应用治疗新型冠状病毒感染的临床研究”中连续给药6天,患者用药期间每天留取的血样检测药物浓度。 研究3 结合研究1中单次给药的药代动力学数据和研究2中用药COVID-19患者的血药浓度数据和药效学(PD)指标,拟合出PK/PD曲线,推测临床最佳使用剂量和雾化频率。 

Objectives of Study:

Study 1 Objective: Safety and tolerability of nebulizer (IFN- + anti-inflammatory factor TFF2) in combination with single dose administration in healthy subjects. Secondary purpose: Pharmacokinetics of atomizer (IFN- + anti-inflammatory factor TFF2) in combination with single dose administration in healthy subjects. Study 2 Detection of early researchers launched a clinical research "antiviral drugs + type Ⅰ interferons + inflammation suppression factor TFF2 combined use of treatment will be coronavirus infection in clinical research" for six days in a row, in patients with drug use during a day to return the blood drug concentration. Study 3 PK/PD curve was fitted by combining the pharmacokinetic data of single dose in study 1 and the blood drug concentration data and pharmacodynamics (PD) indicators of COVID-19 patients in study 2 to infer the optimal clinical dosage and atomization frequency. 

药物成份或治疗方案详述:

 

Description for medicine or protocol of treatment in detail:

 

研究设计:

随机平行对照 

Study design:

Parallel 

纳入标准:

1) 受试者充分了解试验目的、性质、方法以及可能发生的不良反应,自愿作为受试者,并在任何研究程序开始前由本人签署知情同意书,并保证任何程序均将由本人参与研究; 2) 受试者能够和研究者进行良好的沟通,并且理解和遵守本项研究的各项要求者。 3) 受试者无心血管、肝脏、肾脏、呼吸、血液和淋巴、内分泌、免疫、精神、神经、胃肠道系统等慢性疾病史或严重疾病史,并且总体健康状况良好; 4) 受试者(包括男性受试者)在筛选期及未来6个月内无妊娠计划且自愿采取有效避孕措施且无捐精、捐卵计划,其中试验期间应自愿采用非药物避孕措施; 5) 年龄为18~45岁(包括18岁和60岁)的男性或女性受试者; 6) 男性体重≥50.0 kg,女性体重≥45.0 kg;体重指数(BMI)在19.0~26.0 kg/m2范围内(包括临界值); 7) 生命体征检查、体格检查、临床实验室检查(血常规、尿常规、血生化、输血四项、凝血功能、妊娠检查(女性)、酒精及毒品筛查等)、12导联心电图、胸部X片检查及腹部B超检查,结果显示无异常或异常无临床意义者。 

Inclusion criteria

1) The subject fully understands the purpose, nature, method and possible adverse reactions of the study, volunteers to be a subject, and signs the informed consent prior to the commencement of any study procedure, and warrants that he/she will participate in any study procedure; 2) The subject can have good communication with the researcher, and understand and comply with the requirements of this study; 3) Subjects have no history of chronic or serious diseases such as cardiovascular, liver, kidney, respiratory, blood, lymphatic, endocrine, immune, mental, neurological, gastrointestinal system and other diseases, and are in good general health condition; 4) Subjects (including male subjects) have no pregnancy plan during the screening period and in the next 6 months and are willing to take effective contraceptive measures and have no sperm or egg donation plan, among which non-drug contraceptive measures should be adopted voluntarily during the test; 5) Male or female subjects aged from 18 to 45 years (including 18 and 60 years old); 6) Male weight >=50.0kg, female weight >=45.0kg;Body mass index (BMI) was within the range of 19.0~26.0 kg/m2 (including the critical value); 7) Vital signs examination, physical examination, clinical laboratory examination (blood routine, urine routine, blood biochemistry, four items of blood transfusion, coagulation function, pregnancy examination (female), alcohol and drug screening, etc.), 12-lead electrocardiogram, chest X-ray examination and abdominal B-ultrasound examination, and the results show no abnormality or no clinical significance. 

排除标准:

1) 健康状况:有心、肝、肾、消化道、神经系统、呼吸系统、血液和淋巴系统、免疫系统、精神异常及代谢异常及骨骼等有临床意义的病史; 2) 对生物制剂或任意药物组分有过敏史者;曾有过敏史经研究者判定不宜入组者; 3) 在筛选前3个月内接受过手术,或者计划在研究期间进行手术者,及凡接受过会影响药物吸收、分布、代谢、排泄的手术者; 4) 不能耐受静脉穿刺或有晕针晕血史者; 5) 筛选前6个月内有药物滥用史者; 6) 筛选前3个月内使用过毒品; 7) 筛选前3个月内献血包括成分血或大量失血(≥200mL),接受输血或使用血制品者; 8) 受试者(女性)在筛选期或试验过程中处在妊娠期或哺乳期; 9) 受试者在筛选期及未来6个月内有生育计划或捐精、捐卵计划; 10) 筛选前2周内使用过任何处方药、非处方药、中草药者; 11) 筛选前4周内接受过疫苗接种,或者计划在研究期间进行疫苗接种者; 12) 筛选前3个月内每日吸烟量大于5支,或试验期间不能停止使用任何烟草类产品者; 13) 筛选前3个月内每周饮酒量大于14单位(1单位酒精≈360 mL啤酒或45 mL酒精含量为40%的烈酒或150 mL葡萄酒),或试验期间不能禁酒者; 14) 对饮食有特殊要求,不能接受统一饮食者; 15) 筛选前3个月内参加过药物临床试验并使用了试验药物者; 16) 筛选前接受过免疫抑制剂或单克隆抗体; 17) 生命体征检查异常有临床意义者,参考正常值范围(包括临界值):坐位收缩压90~139mmHg,舒张压60~89mmHg,脉搏60-100次/分,体温(耳温)35.4~37.7℃,呼吸16~20次/分,具体情况由研究者综合判定; 18) 实验室检查及辅助检查任何项目异常并经研究者判断有临床意义者; 19) 乙肝病毒学指标、丙型肝炎病毒抗体、抗人类免疫缺陷病毒抗体或抗梅毒螺旋体特异性抗体检查有一项或一项以上有临床意义者; 20) 女性受试者在筛选期尿或血妊娠检查结果阳性者; 21)酒精呼气试验结果大于0.0mg/100mL者或毒品筛查阳性者(吗啡、冰毒(甲基安非他明)、氯胺酮、摇头丸(二亚甲基双氧安非他明)、大麻(四氢大麻酚酸); 22) 自筛选至-1天入院期间发生急性疾病者; 23) 自筛选至-1天入院期间服用了任何处方药、非处方药、中草药者; 24) 研究者判定受试者有任何不适宜参加试验的情况 

Exclusion criteria:

1) Health status: medical history of heart, liver, kidney, digestive tract, nervous system, respiratory system, blood and lymphatic system, immune system, mental and metabolic abnormalities, bone and other diseases with clinical significance; 2) Allergy to biological agents or any drug components;Those who had a history of allergy and were judged unfit for inclusion by the researcher; 3) Those who have undergone surgery within 3 months prior to screening, or plan to undergo surgery during the study period, and those who have undergone surgery that may affect drug absorption, distribution, metabolism and excretion; 4) Those who cannot tolerate venipuncture or have a history of fainting needles and blood; 5) Screening those with a history of drug abuse in the previous 6 months; 6) Screening for drug use in the previous 3 months; 7) Screening blood donation including component blood or massive blood loss (>=200mL) within 3 months before receiving blood transfusion or using blood products; 8) The subject (female) is pregnant or lactating during the screening period or during the test; 9) Subject has any family planning or sperm or egg donation plan during the screening period and in the next 6 months; 10) Use any prescription drug, non-prescription drug or Chinese herbal medicine within 2 weeks before screening; 11) Screening those who have received vaccination within 4 weeks prior to the study or plan to receive vaccination during the study period; 12) Screening for smokers who had smoked more than 5 cigarettes per day in the previous 3 months, or could not stop using any tobacco products during the study period; 13) Screening of persons who had consumed more than 14 units of alcohol (1 unit of alcohol ≈360 mL beer or 45 mL spirits of 40% alcohol or 150 mL wine) per week during the first 3 months, or who were unable to abstain from alcohol during the trial period; 14) Those who have special requirements on diet and cannot accept a unified diet; 15) Screening those who have participated in the drug clinical trial and used the experimental drug within the previous 3 months; 16) Received immunosuppressive agents or monoclonal antibodies before screening; 17) For abnormalities of vital signs with clinical significance, the range of normal values (including critical values) shall be referred: sitting systolic blood pressure 90~139mmHg, diastolic blood pressure 60~89mmHg, pulse 60-100 times/min, body temperature (ear temperature) 35.4~37.7 degree C, respiration 16~20 times/min. The specific conditions shall be determined by the researchers; 18) Laboratory examination and auxiliary examination of any item abnormal and clinically significant as determined by the researcher; 19) One or more tests of hepatitis B virology index, hepatitis C virus antibody, anti-human immunodeficiency virus antibody or anti-treponema pallidus specific antibody have clinical significance; 20) Female subjects with positive urine or blood pregnancy test results during screening period; 21) Alcohol breath test results greater than 0.0mg/100mL or drug screening positive (morphine, meth (methylamphetamine), ketamine, ecstasy (dimethylenedioxymethamphetamine), cannabis (tetrahydrocannabinol); 22) Patients with acute illness from screening to -1 day of admission; 23) take any prescription drug, non-prescription drug or Chinese herbal medicine from screening to one day of hospitalization; 24) The investigator determined that the subjects had any ineligibility to participate in the study. 

研究实施时间:

Study execute time:

From2020-11-02To 2023-08-13 

征募观察对象时间:

Recruiting time:

From2020-11-13To 2022-12-13 

干预措施:

Interventions:

组别:

Group 1

样本量:

8

Group:

Group 1

Sample size:

干预措施:

雾化治疗0.2mg IFN-κ/ 0.5 mg TFF2

干预措施代码:

Intervention:

Atomization treatment, 0.2mg IFN-k/ 0.5 mg TFF2

Intervention code:

组别:

Group 2

样本量:

8

Group:

Group 2

Sample size:

干预措施:

雾化治疗1mg IFN-κ/ 2.5 mg TFF2

干预措施代码:

Intervention:

Atomization treatment, 1mg IFN-k/ 2.5 mg TFF2

Intervention code:

组别:

Group 3

样本量:

8

Group:

Group 3

Sample size:

干预措施:

雾化治疗2mg IFN-κ/ 5 mg TFF2

干预措施代码:

Intervention:

Atomization treatment, 2mg IFN-κ/ 5 mg TFF2

Intervention code:

组别:

Group 4

样本量:

8

Group:

Group 4

Sample size:

干预措施:

雾化治疗4mg IFN-κ/ 10 mg TFF2

干预措施代码:

Intervention:

Atomization treatment, 4mg IFN-κ/ 10 mg TFF2

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

上海 

市(区县):

 

Country:

China 

Province:

Shanghai 

City:

 

单位(医院):

上海市公共卫生临床中心 

单位级别:

三级甲等 

Institution
hospital:

Shanghai Public Health Clinical Center  

Level of the institution:

Tertiary A 

测量指标:

Outcomes:

指标中文名:

雾化剂(IFN-κ+抑炎因子TFF2)联合应用单次给药在健康受试者中的安全性、耐受性

指标类型:

主要指标 

Outcome:

Safety and tolerability of atomization (IFN- +TFF2) combined with single dose in healthy volunteers

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

生命体征

指标类型:

主要指标 

Outcome:

Vital signs

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

血药浓度

指标类型:

主要指标 

Outcome:

Blood drug concentration

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

采集人体标本:

Collecting sample(s)
from participants:

标本中文名:

血液

组织:

Sample Name:

blood

Tissue:

人体标本去向

使用后销毁 

说明

Fate of sample:

Destruction after use 

Note:

征募研究对象情况:

Recruiting status:

尚未开始

Not yet recruiting

年龄范围:

Participant age:

最小 Min age 18 years
最大 Max age 60 years

性别:

男女均可

Gender:

Both

随机方法(请说明由何人用什么方法产生随机序列):

由统计软件产生随机号

Randomization Procedure (please state who generates the random number sequence and by what method):

Random Numbers generated by statistical software

盲法:

双盲

Blinding:

Double blind

试验完成后的统计结果(上传文件):

Calculated Results ater
the Study Completed(upload file):

是否共享原始数据:

IPD sharing

Yes

共享原始数据的方式(说明:请填入公开原始数据日期和方式,如采用网络平台,需填该网络平台名称和网址):

2023年12月,发表文章

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url):

Published in December 2023

数据采集和管理(说明:数据采集和管理由两部分组成,一为病例记录表(Case Record Form, CRF),二为电子采集和管理系统(Electronic Data Capture, EDC),如ResMan即为一种基于互联网的EDC:

使用CRF记录和电子管理系统

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture:

CRF and EDC system

数据管理委员会:

Data Managemen Committee:

有/Yes

注册人:

Name of Registration:

 2020-08-15
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