ChiCTR2300077539 版本V1.1 版本创建时间2024/06/04 16:23:11 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：

ChiCTR2300077539 

最近更新日期：

Date of Last Refreshed on：

2023-11-11 15:41:55 

注册时间：

Date of Registration：

2023-11-11 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

评价AC-201片在健康受试者中的安全性、耐受性、药代动力学特征及食物影响：单中心、随机、双盲、安慰剂对照、单次/多次给药剂量递增的 I期临床研究

Public title：

Evaluation of the Safety, Tolerability, Pharmacokinetic Profile, and Food Effects of AC-201 Tablets in Healthy Subjects: a Single-Center, Randomized, Double-Blind, Placebo-Controlled, Single/Multiple Administration Dose Escalating Phase I Clinical Study

注册题目简写：

English Acronym：

研究课题的正式科学名称：

评价AC-201片在健康受试者中的安全性、耐受性、药代动力学特征及食物影响：单中心、随机、双盲、安慰剂对照、单次/多次给药剂量递增的 I期临床研究

Scientific title：

Evaluation of the Safety, Tolerability, Pharmacokinetic Profile, and Food Effects of AC-201 Tablets in Healthy Subjects: a Single-Center, Randomized, Double-Blind, Placebo-Controlled, Single/Multiple Administration Dose Escalating Phase I Clinical Study

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：

张炜 

研究负责人：

胡伟 

Applicant：

Wei Zhang 

Study leader：

Wei Hu 

申请注册联系人电话：

Applicant telephone：

+86 551 6599 7141

研究负责人电话：

Study leader's telephone：

+86 551 6599 7164

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：

zhangpharmacy@163.com

研究负责人电子邮件：

Study leader's E-mail：

ayefygcp@163.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：

安徽省合肥市经开区芙蓉路678号

研究负责人通讯地址：

安徽省合肥市经济开发区芙蓉路678号

Applicant address：

678 Furong Road, ETDZ, Hefei, Anhui Province

Study leader's address：

678 Furong Road, ETDZ, Hefei, Anhui Province

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：

安徽医科大学第二附属医院药物临床试验中心

Applicant's institution：

Drug Clinical Trial Research Center, The Second Affiliated Hospital of Anhui Medical University

研究负责人所在单位：

安徽医科大学第二附属医院药物临床试验中心

Affiliation of the Leader：

Drug Clinical Trial Research Center, The Second Affiliated Hospital of Anhui Medical University

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

YW2023-140(F1)

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：

安徽医科大学第二附属医院药物临床试验伦理委员会

Name of the ethic committee：

Ethics Committee of The Second Hospital of Anhui Medical University

伦理委员会批准日期：

Date of approved by ethic committee：

2023-09-28 00:00:00

伦理委员会联系人：

张静

Contact Name of the ethic committee：

Jing Zhang

伦理委员会联系地址：

安徽省合肥市经开区芙蓉路678号

Contact Address of the ethic committee：

678 Furong Road, ETDZ, Hefei, Anhui Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 551 6380 6061

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：

安徽医科大学第二附属医院药物临床试验中心

Primary sponsor：

Drug Clinical Trial Research Center, The Second Affiliated Hospital of Anhui Medical University

研究实施负责（组长）单位地址：

安徽省合肥市经开区芙蓉路678号

Primary sponsor's address：

678 Furong Road, ETDZ, Hefei, Anhui Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

江苏省

市(区县)：

Country：

China

Province：

Jiangsu

City：

单位(医院)：

爱科诺生物医药（苏州）有限公司

具体地址：

苏州工业园区苏州生物医药产业园

Institution
hospital：

Accro Bioscience (Suzhou) Limited.

Address：

the BioBAY of Suzhou Industrial Park

经费或物资来源：

爱科诺生物医药（苏州）有限公司

Source(s) of funding：

Accro Bioscience (Suzhou) Limited.

Target disease：

Psoriasis

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：

随机平行对照 

Study design：

Parallel 

研究目的：

主要目的：评估健康受试者单次和多次服用AC-201片后的安全性和耐受性； 次要目的： 1. 观察健康受试者单次和多次服用AC-201片后的药代动力学特征； 2. 评估食物对健康受试者口服AC-201片的药代动力学特征的影响； 其他目的：探索单次给药后AC-201 的生物标志物/药效标志物。  

Objectives of Study：

Primary Objectives: To assess the safety and tolerability of AC-201 tablets after single and multiple doses in healthy subjects; Secondary Objectives: 1. To observe the pharmacokinetic profile of AC-201 Tablets after single and multiple doses in healthy subjects; 2. To assess the effect of food on the pharmacokinetic profile of AC-201 Tablets administered orally to healthy subjects; Other Objectives: To explore biomarkers/pharmacodynamic markers of AC-201 after single administration.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1.在进行任何与试验相关的活动前，必须签署书面知情同意书，且必须了解试验的性质和目的，包括可能存在的风险和不良反应； 2.筛选时，年龄在18至60周岁（含）之间，男女不限； 3.筛选时，体重指数（BMI）=体重（kg）/ （身高）2（m2），BMI在19.0 ~ 28.0 kg/m2（含临界值）；男性受试者体重 ≥ 50 kg，女性受试者体重 ≥ 45 kg； 4.生命体征、体格检查、12-导联心电图、实验室检查（血常规、尿常规、血生化、凝血功能等）正常或经研究者评估为异常无临床意义者； 5.若为女性受试者必须满足：a. 不具有生育能力，即经外科手术绝育（至少在筛选前6周进行了子宫切除术/双侧输卵管切除术/双侧卵巢切除术）或已绝经（已绝经定义为超过12个月无月经，并排除其他医学原因）；或b. 若为育龄期女性，则必须在筛选（血液检查）时和首次试验药物给药前（D-1）妊娠试验呈阴性，其必须同意从签署知情同意书至试验药物最后一次给药后至少3个月内无生育以及捐卵计划且自愿采取有效的非药物避孕措施；若为男性受试者，若未经外科手术绝育，则必须同意从签署知情同意书至试验药物最后一次给药后至少3个月内无生育以及捐精计划且自愿采取有效的非药物避孕措施； 6.愿意且能够接受所有试验评估，并遵守方案时间表和限制条件。

Inclusion criteria

1. Written informed consent must be signed prior to any trial-related activity and the characteristic and purpose of the trial, including possible risks and adverse reactions, must be well understood; 2. Those who aged between 18 and 60 years old (inclusive) at screening, male or female; 3. Male subjects weighing ≥ 50 kg, female subjects weighing ≥ 45 kg and their BMI between 19.0 ~ 28.0 kg/m2 (including the threshold value) at screening; 4. Vital signs, physical examination, 12-lead electrocardiogram, laboratory tests (routine blood, urine, blood biochemistry, coagulation function, etc.) are normal or assessed by the investigator as abnormal without clinical significance; 5. In the case of female subjects must meet the following criteria: a. no childbearing potential, i.e., surgically sterilized (hysterectomy/bilateral salpingo-oophorectomy/bilateral salpingo-oophorectomy at least 6 weeks prior to screening) or menopausal (menopausal is defined as the absence of menstruation for a period of more than 12 months and other medical reasons are ruled out); or b. in the case of females of childbearing potential, the test medication must have been administered to the female at the time of screening (blood test) and at the time of the first test drug (D-1) pregnancy test negative at screening (blood test) and prior to administration of the first dose of the test drug, and must agree to be free of childbearing and egg donation and to voluntarily use effective non-pharmacological contraception for at least 3 months from the time of signing of the Informed Consent Form to the date of the last administration of the test drug; or, in the case of a male subject who has not been surgically sterilized, must agree to be free of childbearing and sperm donation and voluntarily use effective non-pharmacological contraception for at least 3 months from the time of signing of the Informed Consent Form to the date of the last administration of the test drug; and Be willing to use effective non-pharmacological contraception; 6. Be willing and able to undergo all trial evaluations and comply with the protocol schedule and restrictions.

排除标准：

1.有心血管、呼吸、消化、肝脏、泌尿、血液、内分泌、代谢、免疫、皮肤或精神神经系统慢性疾病史，也包括由研究者确定与临床相关的筛选前3个月内的外科手术或筛选前2周内任何急性疾病史，且经研究者评估为异常有临床意义者； 2.筛选期前 30 天内使用过任何抑制或诱导肝脏药物代谢酶的药物；试验开始给药前7天内服用过含有可诱导或抑制肝脏代谢酶的食物或饮料（如葡萄柚等）者；不同意或无法保证在试验首次给药前48h至完成最后一个药代动力学血样采集期间停止摄取任何含有或代谢后产生咖啡因或黄嘌呤食物或饮料（如咖啡、茶、巧克力等）者；或对饮食有特殊要求，不能遵守规定饮食者； 3.入选食物影响组的受试者有饮食限制（如乳糖不耐受）或无法进食高脂肪餐者； 4.患有胃肠道、肝脏、肾脏或其他已知干扰药物吸收、分布、代谢或排泄的疾病的后遗症者； 5.当前患有需要使用抗生素、抗真菌药、抗寄生虫药或抗病毒药治疗的感染者； 6.有任何恶性肿瘤疾病史者； 7.在试验期间或试验药物首次给药前4个月内，使用或计划使用全身性免疫抑制剂（包括但不限于皮质类固醇、甲氨蝶呤、硫唑嘌呤、环孢素）或免疫调节药物（包括但不限于干扰素）；使用试验药物前14天内服用过任何处方药、非处方药、中草药或保健品者（注：在给药前48小时允许使用<2g/天的对乙酰氨基酚）；若既往用药的半衰期较长，试验药物首次给药前所需的时间间隔至少为该药物的5个半衰期； 8.血清肌酐值超过正常值上限或肾小球滤过率eGFR <90 mL/min/1.73m2； 9.筛选时经Fridericia’s公式校正的 QT 间期（QTcF），男性>450 msec，女性>470 msec者； 10.乙肝表面抗原、丙型肝炎抗体、人类免疫缺陷病毒抗体、梅毒螺旋体抗体任意一项检查阳性者； 11.筛选前3个月每周饮酒超过14 单位酒精（1单位=360 mL 啤酒或 45 mL 酒精量为 40%的烈酒或150 mL 葡萄酒）；或随机前血液酒精测试结果呈阳性者； 12.筛选前3个月内每日吸烟量大于5支或习惯性使用含尼古丁制品，在首次试验药物给药前1个月内吸烟（包括烟草、电子烟和大麻）； 13.筛选前3个月内有药物滥用史（包括非医疗目的反复、大量地使用各类麻醉药品和精神药品）或毒品筛查（包括：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）、可卡因等）阳性者； 14.有药物、食物等过敏史；或已知对任何研究药物成分过敏者； 15.妊娠、哺乳期女性； 16.在试验药物首次给药前3个月内献血或失血≥450 mL；或在筛选前1个月内献血或失血≥200 mL；或计划在试验期间献血；或在试验药物首次给药前1年内接受输血； 17.在试验药物首次给药前3个月内入组过任何其他研究性临床试验； 18.不能耐受静脉穿刺或有晕针晕血史者； 19.研究者认为受试者有不适合该试验的既往治疗史或任何其他情况，包括无法完全配合试验方案的要求或可能不符合某些试验要求。

Exclusion criteria：

1. A history of chronic disease of the cardiovascular, respiratory, gastrointestinal, hepatic, urologic, hematologic, endocrine, metabolic, immunologic, dermatologic, or psychoneurologic systems, including surgery within 3 months prior to screening as determined by the investigator to be clinically relevant, or any history of acute illness within 2 weeks prior to screening that is assessed by the investigator to be clinically significant as an abnormality; 2. Use of any drug that inhibits or induces hepatic drug-metabolizing enzymes within 30 days prior to screening; consumption of food or beverages containing foods or beverages (e.g., grapefruit, etc.) that induce or inhibit hepatic drug-metabolizing enzymes within 7 days prior to the start of trial dosing; and disagreement or inability to ensure that ingestion of any food or beverage (e.g., coffee, tea, tea, etc.) that contains or that is metabolized to produce caffeine or xanthines will be discontinued from the period of 48 h prior to the first dose of the trial to the time of the last pharmacokinetic blood sample collection. 3. Subjects enrolled in the Food Effect Group have dietary restrictions (e.g., lactose intolerance) or are unable to consume high-fat meals; 4. Those with sequelae of gastrointestinal, hepatic, renal, or other disorders known to interfere with drug absorption, distribution, metabolism, or excretion; 5. Those with current infections requiring treatment with antibiotics, antifungals, antiparasites, or antivirals; 6. Those with a history of any malignant disease; 7. Use or planned use of systemic immunosuppressants (including but not limited to corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulatory drugs (including but not limited to interferon) during the trial or within 4 months prior to the first administration of the test drug; use of any prescription, over-the-counter, herbal, or nutraceutical medication within 14 days prior to the use of the test drug (NOTE: use of <2 g/day of acetaminophen at 48 hours prior to the administration of the test drug is allowed); if the half-life of previous medication is long, the time interval required before the first administration of the test drug is at least 5 half-lives of the drug; 8. Serum creatinine value exceeding the upper limit of normal or glomerular filtration rate (eGFR) <90 mL/min/1.73m2; 9. The QT interval (QTcF) corrected by Fridericia's formula at screening is >450 msec in men and >470 msec in women; 10. Those who have a positive test for any of the Hepatitis B Surface Antigen, Hepatitis C Antibody, Human Immunodeficiency Virus Antibody, or Syphilis Spirochete Antibody; 11. Drinking more than 14 units of alcohol per week (1 unit = 360 mL of beer or 45 mL of 40% alcohol spirits or 150 mL of wine) in the 3 months prior to screening; or having a positive blood alcohol test result before randomization; 12. Smoking greater than 5 cigarettes per day or habitual use of nicotine-containing products in the 3 months prior to screening, and smoking (including tobacco, e-cigarettes, and marijuana) in the 1 month prior to the first administration of the trial drug; 13. Those who have a history of substance abuse (including repeated, heavy use of all types of narcotic drugs and psychotropic substances for non-medical purposes) or a positive drug screening (including: morphine, methamphetamine, ketamine, ecstasy, tetrahydrocannabinolic acid, and cocaine, etc.) in the 3 months prior to screening; 14. History of allergy to drugs, food, etc.; or known allergy to any of the components of the study drug; 15. Pregnant or lactating females; 16. Those who donated or lost ≥ 450 mL of blood within 3 months prior to the first administration of the test drug; or donated or lost ≥ 200 mL of blood within 1 month prior to screening; or planned to donate blood during the trial; or received a blood transfusion within 1 year prior to the first administration of the test drug; 17. Those who has been enrolled in any other clinical trial within 3 months prior to the first administration of the test drug; 18. Those who cannot tolerate venipuncture or has a history of needle and blood sickness; 19. Those who, in the opinion of the investigator, have a history of prior treatment that is inappropriate for the trial or any other condition, including inability to fully cooperate with the requirements of the trial protocol or may not meet certain trial requirements.

研究实施时间：

Study execute time：

从 From 2023-11-15 00:00:00至 To 2024-05-15 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2023-11-17 00:00:00 至 To 2024-05-15 00:00:00  

干预措施：

Interventions：

组别：

单次给药剂量组

样本量：

40

Group：

Single Dose Group

Sample size：

干预措施：

空腹口服AC-201片(5~200 mg)或安慰剂一次。

干预措施代码：

Intervention：

Orally administration of AC-201 tablets (5 to 200 mg) or placebo once under fasting condition.

Intervention code：

组别：

食物影响研究

样本量：

12

Group：

Food Effect Study

Sample size：

干预措施：

其中6例在第一周期完成空腹单次给药，经过3天洗脱期，在第二周期完成高脂餐后单次给药。另6例则在第一周期完成高脂餐后单次给药，经过3天洗脱期，在第二周期完成空腹单次给药。

干预措施代码：

Intervention：

Six of these subjects completed a single dose under fasting condition in the first cycle and, after a 3-day washout period, completed a single dose with a high-fat meal in the second cycle. The other 6 subjects completed a single dose with high-fat meal in the first cycle, followed by a 3-day washout period and completed a single dose under fasting condition in the second cycle.

Intervention code：

组别：

多次给药剂量组

样本量：

30

Group：

Multiple dose group

Sample size：

干预措施：

3个剂量组：15 mg（qd），15 mg（bid）和50 mg（qd）剂量组，均连续给药5天。

干预措施代码：

Intervention：

Three dose groups: 15 mg (qd), 15 mg (bid) and 50 mg (qd) dose groups were administered for 5 consecutive day.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 安徽省 

市(区县)：

  

Country：

China 

Province：

Anhui 

City：

 

单位(医院)：

安徽医科大学第二附属医院药物临床试验中心 

单位级别：

三甲 

Institution
hospital：

Drug Clinical Trial Research Center, The Second Affiliated Hospital of Anhui Medical University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

安全结局

指标类型：

主要指标

Outcome：

Safty and tolerance

Type：

Primary indicator

测量时间点：

测量方法：

将通过观察不良事件（AE）、生命体征、体格检查、实验室检查（血常规、血生化、尿常规和凝血功能）、12-导联心电图等评估安全性与耐受性

Measure time point of outcome：

Measure method：

指标中文名：

PK 指标

指标类型：

次要指标

Outcome：

PK outcome (Plasma concentration)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

PD指标

指标类型：

附加指标

Outcome：

PD outcome

Type：

Additional indicator

测量时间点：

测量方法：

检测给药后不同时间点的血浆样本对外周血单核细胞（PBMC）中IFN-α激活TYK2 介导的标记物CXCL-10的抑制作用和给药后不同时间点的血浆样本对PBMC中IL-12激活TYK2 介导的标记物IFN-γ的抑制作用。

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 60 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）：

区组随机

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

Block randomization

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

双盲

Blinding：

double blinding

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

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）：

数据录入EDC系统(https://dastrial.drugchina.net/edc/home/subject/flow?siteid=1652323812354&real_siteid=1652323812354&subjectid=31&originalPage=dashboard&pageSource=visitMatrix)

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

Data entry into EDC system (https://dastrial.drugchina.net/edc/home/subject/flow?siteid=1652323812354&real_siteid=1652323812354&subjectid=31&originalPage=dashboard&pageSource=visitMatrix)

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：

数据录入EDC系统(https://dastrial.drugchina.net/edc/home/subject/flow?siteid=1652323812354&real_siteid=1652323812354&subjectid=31&originalPage=dashboard&pageSource=visitMatrix)

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

Data entry into EDC system (https://dastrial.drugchina.net/edc/home/subject/flow?siteid=1652323812354&real_siteid=1652323812354&subjectid=31&originalPage=dashboard&pageSource=visitMatrix)

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：

  2023-11-11 15:41:21