ChiCTR2300073285 版本V1.1 版本创建时间2023/09/03 12:16:25 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

 ChiCTR2300073285 

最近更新日期：

Date of Last Refreshed on：

 2023-07-06 08:44:31 

注册时间：

Date of Registration：

 2023-07-06 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

评估KN056在中国健康受试者中单次皮下注射给药的安全性、耐受性、药代动力学、药效学的剂量递增研究

Public title：

A dose-escalation study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of KN056 administered as a single subcutaneous injection in healthy Chinese subjects

注册题目简写：

English Acronym：

研究课题的正式科学名称：

评估KN056在中国健康受试者中单次皮下注射给药的安全性、耐受性、药代动力学、药效学的剂量递增研究

Scientific title：

A dose-escalation study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of KN056 administered as a single subcutaneous injection in healthy Chinese subjects

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：

张圣婷 

研究负责人：

阳国平 

Applicant：

Shengting Zhang 

Study leader：

Guoping Yang 

申请注册联系人电话：

Applicant telephone：

 +86 188 4576 6257

研究负责人电话：

Study leader's
telephone：

+86 731 8991 8665

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：

 1456499839@qq.com

研究负责人电子邮件：

Study leader's E-mail：

 ygp9880@126.com

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：

湖南省长沙市岳麓区桐梓坡路138号

研究负责人通讯地址：

湖南省长沙市岳麓区桐梓坡路138号

Applicant address：

138 Tongzipo Road, Yuelu District, Changsha, Hu'nan

Study leader's address：

138 Tongzipo Road, Yuelu District, Changsha, Hu'nan

申请注册联系人邮政编码：

Applicant postcode：

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

中南大学湘雅三医院临床试验中心

Applicant's institution：

Clinical Trial Center of the Third Xiangya Hospital of Central South University

研究负责人所在单位：

中南大学湘雅三医院临床试验中心

Affiliation of the Leader：

Clinical Trial Center of the Third Xiangya Hospital of Central South University

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：

 23064

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：

中南大学湘雅三医院伦理委员会

Name of the ethic committee：

IRB of theThird Xiangya Hospital of Central South University

伦理委员会批准日期：

Date of approved by ethic committee：

 2023-04-19 00:00:00

伦理委员会联系人：

王晓敏

Contact Name of the ethic committee：

Wang Xiaomin

伦理委员会联系地址：

湖南省长沙市岳麓区桐梓坡路138号中南大学湘雅三医院伦理委员会

Contact Address of the ethic committee：

138 Tongzipo Road, Yuelu District, Changsha, Hu'nan

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 731 8861 8938

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：

中南大学湘雅三医院临床试验中心

Primary sponsor：

Clinical Trial Center of the Third Xiangya Hospital of Central South University

研究实施负责（组长）单位地址：

湖南省长沙市岳麓区桐梓坡路138号

Primary sponsor's address：

138 Tongzipo Road, Yuelu District, Changsha, Hu'nan

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

湖南

市(区县)：

长沙

Country：

China

Province：

Hunan

City：

Changsha

单位(医院)：

中南大学湘雅三医院

具体地址：

岳麓区桐梓坡路138号

Institution
hospital：

Third Xiangya Hospital, Central South University

Address：

138 Tongzipo Road, Yuelu District

经费或物资来源：

苏州康宁杰瑞生物科技有限公司

Source(s) of funding：

Suzhou Canning Jereh Biotechnology Co.

研究疾病：

糖尿病  

Target disease：

Diabetes

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：

 I期临床试验 

Study phase：

1

研究设计：

不同剂量对照 

Study design：

Dose comparison 

研究目的：

主要目的： ? 评价 KN056 在中国健康受试者中单次皮下注射给药的安全性和耐受性； ? 评价 KN056 在中国健康受试者中单次皮下注射给药的药代动力学特征。 次要目的： ? 评价 KN056 在中国健康受试者中单次皮下注射给药的免疫原性； ? 评价 KN056 在中国健康受试者中单次皮下注射给药对药效学指标的影响； ? 初步评价 KN056 的剂量-效应关系。  

Objectives of Study：

Primary objective: - To evaluate the safety and tolerability of KN056 administered as a single subcutaneous injection in healthy Chinese subjects; - To evaluate the pharmacokinetic profile of KN056 administered as a single subcutaneous injection in healthy Chinese subjects. Secondary objectives: - To evaluate the immunogenicity of KN056 administered as a single subcutaneous injection in healthy Chinese subjects; - To evaluate the effect of single subcutaneous administration of KN056 on pharmacodynamic indices in healthy Chinese subjects; - Preliminary evaluation of the dose-effect relationship of KN056.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

入选标准 1) 健康男性或女性； 2) 在签署知情同意时，年龄在 18 至 55 周岁之间（包括界值）； 3) BMI：20.0 kg/m2≤BMI＜28 kg/m2； 4) HbA1c<6.5%；3.9mmol/L≤空腹血糖水平<7.0mmol/L；糖负荷后 2h 血糖<11.1mmol/L； 5) 能够理解并愿意遵守临床试验方案完成本试验，自愿签署知情同意书。

Inclusion criteria

Inclusion criteria 1) Healthy male or female; 2) Between the ages of 18 and 55 years (including cut-offs) at the time of signing informed consent; 3) BMI: 20.0 kg/m2 ≤ BMI < 28 kg/m2; 4) HbA1c < 6.5%; 3.9 mmol/L ≤ fasting blood glucose level < 7.0 mmol/L; 2h post-glucose load blood glucose < 11.1 mmol/L; 5) Able to understand and willing to comply with the clinical trial protocol to complete the trial and voluntarily sign the informed consent form.

排除标准：

1) 既往有慢性疾病病史或目前存在研究者判断有临床意义的系统性疾病，如：心血管系统、呼吸系统、内分泌和代谢系统、泌尿系统、消化系统、血液系统、自身免疫性疾病、神经系统疾病或精神病学疾病、细菌或病毒感染等； 2) 急性或慢性胰腺炎病史；有髓样甲状腺癌或多发性内分泌腺瘤综合征 2 型(MEN2)个人史或家族史；其他恶性肿瘤史； 3) 既往有胃肠道疾病史(如食管反流或胆囊疾病)或任何影响胃排空的胃肠道疾病/手术(如胃旁路手术、幽门狭窄，阑尾切除术除外)或胰高血糖素样肽-1 受体激动剂（GLP-1RA）或二肽基肽酶-4 抑制剂（DPP-4i）可加重的胃肠道疾病； 4) 既往曾行胆囊结石清除或胆囊切除术； 5) 对试验用药品及辅料或者 GLP-1 类药物过敏； 6) 筛选（签署 ICF）前 1 年内有药物滥用/依赖史或有毒品吸入/注射史；尿液药物滥用筛查阳性； 7) 酒精呼气检测结果阳性（> 0 mg/100 mL）； 8) 筛选前 3 个月内接受过任何重大手术或影响药物吸收、分布、代谢、排泄的手术，或计划在试验期间进行手术（重大手术定义为针对颅内、胸部、腹部、盆腔或四肢器官，导致组织重大创伤，需要长期恢复的手术）； 9) 筛选前 3 个月内或筛选期内每周饮酒超过 14 单位酒精（1 单位=360ml 啤酒或 45ml 酒精量为 40%的烈酒或 150ml 葡萄酒），住院期间不能禁酒，出院后访视期内不能限制每日饮酒少于 2 单位酒精； 10) 筛选前 3 个月内献血或失血≥300ml（女性生理性失血除外），或计划在试验期间或试验结束后 1 个月内献血或献血液成分； 11) 筛选前 2 个月内接受过其它药物/疫苗临床试验的给药；筛选时处于其它临床试验中； 12) 筛选前 14 天内接受了疫苗接种，或计划在临床试验期间接受接种，包括灭活疫苗、减毒活疫苗、重组蛋白疫苗、重组腺病毒疫苗、RNA 疫苗、DNA 疫苗、COVID-19 疫苗; 13) 给药前 14 天内使用过任何处方药、非处方药或中草药（除维生素/矿物质补充剂、对乙酰氨基酚、局部外用药和避孕药）； 14) 给药前 1 个月内使用过 GLP-1 类似物、GLP-1 受体激动剂或任何其它肠促胰岛素相关处方制剂以及其他研究者认为可能影响试验的药物； 15) 体格检查、生命体征、心电图、临床实验室等检查结果经研究者判断异常且有临床意义，且可能对本试验结果评估有影响或可能增加受试者风险； 16) 传染病筛查阳性：肝炎（包括乙肝和丙肝）及艾滋病、梅毒筛选阳性者； 17) 妊娠期、哺乳期或妊娠试验阳性的女性受试者； 18) 不能保证在筛选期至给药后3个月内禁欲或采取有效的避孕措施或在筛选期至给药后3个 月内有生育计划者； 19) 给药后 3 个月内有捐献精子/卵子计划者； 20) 因外伤、手术、过敏或皮肤病变等原因导致腹部皮肤不适合进行皮下注射； 21) 研究者认为有不适于参加试验的其他情况，或签署 ICF 后因受试者自身原因不能参加试验等情况。

Exclusion criteria：

1) a prior history of chronic disease or the current presence of a systemic disease that in the judgment of the investigator is clinically significant, such as: cardiovascular, respiratory, endocrine and metabolic, urinary, digestive, hematologic, autoimmune, neurological or psychiatric disorders, bacterial or viral infections 2) history of acute or chronic pancreatitis; personal history or family history of medullary thyroid cancer or multiple endocrine adenoma syndrome type 2 (MEN2); history of other malignancies 3) previous history of gastrointestinal disease (e.g., esophageal reflux or gallbladder disease) or any gastrointestinal disease/surgery affecting gastric emptying (e.g., gastric bypass surgery, pyloric stenosis, except appendectomy) or gastrointestinal disease that can be exacerbated by glucagon-like peptide-1 receptor agonists (GLP-1RA) or dipeptidyl peptidase-4 inhibitors (DPP-4i) 4) previous gallbladder stone removal or cholecystectomy; 5) hypersensitivity to the test drug and excipients or GLP-1 class drugs; 6) history of drug abuse/dependence or history of drug inhalation/injection within 1 year prior to screening (signing ICF); positive urine drug abuse screen; 7) Positive alcohol breath test result (> 0 mg/100 mL); 8) Any major surgery or surgery affecting drug absorption, distribution, metabolism, excretion within 3 months prior to screening or planned during the trial (major surgery is defined as surgery targeting intracranial, thoracic, abdominal, pelvic, or extremity organs that results in significant tissue trauma requiring long-term recovery) 9) Drinking more than 14 units of alcohol per week (1 unit = 360 ml of beer or 45 ml of spirits at 40% alcohol or 150 ml of wine) within 3 months prior to screening or during the screening period, not being able to abstain from alcohol during hospitalization, and not being able to limit drinking to less than 2 units of alcohol per day during the post-discharge visit; 10) blood donation or blood loss ≥ 300 ml within 3 months prior to screening (except for physiological blood loss in women), or planned blood donation or blood component donation during the trial or within 1 month after the end of the trial; 11) have received administration of another drug/vaccine clinical trial within 2 months prior to screening; are in another clinical trial at the time of screening 12) Received a vaccination within 14 days prior to screening or is scheduled to receive a vaccination during the clinical trial, including inactivated vaccine, live attenuated vaccine, recombinant protein vaccine, recombinant adenovirus vaccine, RNA vaccine, DNA vaccine, COVID-19 vaccine. 13) Use of any prescription, over-the-counter, or herbal medication (except vitamin/mineral supplements, acetaminophen, topical topicals, and contraceptives) within 14 days prior to dosing; 14) Use of GLP-1 analogs, GLP-1 receptor agonists or any other entero-insulin-related prescription preparations and other drugs that, in the opinion of the investigator, may interfere with the trial within 1 month prior to dosing 15) Physical examination, vital signs, electrocardiogram, clinical laboratory and other findings that are abnormal and clinically significant in the judgment of the investigator and that may have an impact on the evaluation of the results of this trial or may increase the risk to the subject; 16) Positive screening for infectious diseases: hepatitis (including hepatitis B and C) and positive screening for AIDS and syphilis; 17) Female subjects who are pregnant, lactating, or have a positive pregnancy test; 18) Those who cannot guarantee abstinence or use effective contraceptive measures during the screening period to 3 months after dosing or 18) Female subjects who cannot be assured of abstinence or effective contraceptive use between the screening period and 3 months after dosing or who have a childbearing plan between the screening period and 3 months after dosing 19) Sperm/egg donor within 3 months of dosing 20) abdominal skin unsuitable for subcutaneous injection due to trauma, surgery, allergy or skin lesions 21) Any other condition that the investigator deems unsuitable for participation in the trial, or if the subject is unable to participate in the trial for his or her own reasons after signing the ICF.

研究实施时间：

Study execute time：

从 From 2023-07-05 00:00:00至 To 2025-07-06 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2023-07-06 00:00:00 至 To 2025-07-05 00:00:00

干预措施：

Interventions：

组别：

1.0mg

样本量：

 3

Group：

1.0mg

Sample size：

干预措施：

均接受KN056

干预措施代码：

Intervention：

All accept KN056

Intervention code：

组别：

3.0mg

样本量：

 8

Group：

3.0mg

Sample size：

干预措施：

其中前 2 例受试者为哨兵，1:1 随机接受KN056 或 KN056 安慰剂，哨兵给药至少 3 天后经研究者判断可启动剩余 6 例受试者的给药

干预措施代码：

Intervention：

The first 2 subjects were sentinels, randomized 1:1 to receive either KN056 or KN056 placebo, and at least 3 days after sentinel dosing, at the discretion of the investigator, dosing could be initiated in the remaining 6 subjects

Intervention code：

组别：

6.0mg

样本量：

 8

Group：

6.0mg

Sample size：

干预措施：

其中前 2 例受试者为哨兵，1:1 随机接受KN056 或 KN056 安慰剂，哨兵给药至少 3 天后经研究者判断可启动剩余 6 例受试者的给药

干预措施代码：

Intervention：

The first 2 subjects were sentinels, randomized 1:1 to receive either KN056 or KN056 placebo, and at least 3 days after sentinel dosing, at the discretion of the investigator, dosing could be initiated in the remaining 6 subjects

Intervention code：

组别：

12.0mg

样本量：

 8

Group：

12.0mg

Sample size：

干预措施：

其中前 2 例受试者为哨兵，1:1 随机接受KN056 或 KN056 安慰剂，哨兵给药至少 3 天后经研究者判断可启动剩余 6 例受试者的给药

干预措施代码：

Intervention：

The first 2 subjects were sentinels, randomized 1:1 to receive either KN056 or KN056 placebo, and at least 3 days after sentinel dosing, at the discretion of the investigator, dosing could be initiated in the remaining 6 subjects

Intervention code：

组别：

20.0mg

样本量：

 8

Group：

20.0mg

Sample size：

干预措施：

其中前 2 例受试者为哨兵，1:1 随机接受KN056 或 KN056 安慰剂，哨兵给药至少 3 天后经研究者判断可启动剩余 6 例受试者的给药

干预措施代码：

Intervention：

The first 2 subjects were sentinels, randomized 1:1 to receive either KN056 or KN056 placebo, and at least 3 days after sentinel dosing, at the discretion of the investigator, dosing could be initiated in the remaining 6 subjects

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 湖南 

市(区县)：

 长沙 

Country：

China

Province：

Hunan

City：

Changsha

单位(医院)：

 中南大学湘雅三医院 

单位级别：

 三甲 

Institution
hospital：

Third Xiangya Hospital, Central South University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

药物注射后不良事件的发生率

指标类型：

主要指标

Outcome：

Incidence of adverse events after drug injection

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

AUC0-t

指标类型：

主要指标

Outcome：

AUC0-t

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

MRT

指标类型：

主要指标

Outcome：

MRT

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

抗药抗体

指标类型：

次要指标

Outcome：

ADA

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

口服葡萄糖耐量试验

指标类型：

次要指标

Outcome：

OGTT

Type：

Secondary 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 岁 years
最大 Max age 55 岁 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）：

合格的受试者按照筛选成功从小到大的顺序获得随机号，Cohort 1 随机号为 1001-1003， Cohort 2 随机号为 2001-2008，Cohort 3 随机号为 3003-3008，Cohort 4 随机号为 4001-4008， Cohort 5 随机号为 5001-5008。 Cohort 1 入组 3 例受试者，均接受 KN056；Cohort 2 至 Cohort 5 每个剂量组分别入组 8 例 受试者，其中先入组的 2 例哨兵 1:1 随机接受 KN056 或 KN056 安慰剂，再入组的 6 例受试者 按 5:1 的比例随机接受 KN056：KN056 安慰剂。

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

Eligible subjects were given random numbers in descending order of screening success, with Cohort 1 random numbers being 1001-1003, Cohort 2 random numbers being 2001-2008, Cohort 3 random numbers being 3003-3008, and Cohort 4 random numbers being 4001-4008. Cohort 2 random numbers were 2001-2008, Cohort 3 random numbers were 3003-3008, Cohort 4 random numbers were 4001-4008, and Cohort 5 random numbers were 5001-5008. Cohort 5 was randomized to 5001-5008. Cohort 1 enrolled 3 subjects who received KN056; Cohort 2 to Cohort 5 enrolled 8 subjects in each dose group. The first 2 sentinels were randomized 1:1 to receive either KN056 or KN056 placebo, and the next 6 subjects were randomized 5:1 to receive either KN056 or KN056 placebo. were randomized to receive KN056:KN056 placebo in a 5:1 ratio.

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：

Blinding：

是否共享原始数据：

IPD sharing

否No

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）：

否

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

NO

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：

本研究将采用电子数据采集（EDC）系统，在研究中心发生的本研究数据将被录入至数据库。数据录入将由研究者指定授权的研究人员完成。在研究启动前和开始录入任何受试者的数据前，研究者和其授权的研究人员将接受适当的培训和保密措施培训。 研究者应为每个随机进入研究的受试者准备原始文件，内容应全面、准确，以便记录所有检查结果及其他相关数据，并妥善保存这些文件。 研究者负责维护原始文件，在监查员每次做监查访视时，研究者必须提供原始文件给监察员查阅。研究者参加研究即表示其同意这个研究的结果可能用于向国家和/或国际注册和监管机构提交资料。

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

This study will use an electronic data capture (EDC) system and data from this study occurring at the study center will be entered into a database. Data entry will be done by authorized investigators designated by the investigator. The investigator and his/her authorized investigator will receive appropriate training and training on confidentiality measures prior to study initiation and prior to the start of data entry for any subject. The investigator shall prepare original documentation for each subject randomized into the study that is comprehensive and accurate in order to record all test results and other relevant data, and shall maintain such documentation appropriately. The investigator is responsible for maintaining the original documentation, which must be made available to the monitor for review at each monitoring visit by the monitor. By participating in the study, the investigator agrees that the results of this study may be used to submit information to national and/or international registration and regulatory agencies.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2023-07-06 08:43:52