ChiCTR2100054035 版本V1.1 版本创建时间2022/11/06 15:14:20 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：

ChiCTR2100054035 

最近更新日期：

Date of Last Refreshed on：

2022-06-01 11:54:14 

注册时间：

Date of Registration：

2021-12-07 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

应用胎盘提取热休克蛋白制剂治疗强直性脊柱炎、系统性红斑狼疮等自身免疫疾病的前导性临床研究

Public title：

A pilot clinical study of heat shock protein preparation extracted from placenta in the treatment of autoimmune diseases such as ankylosing spondylitis and systemic lupus erythematosus etc.

注册题目简写：

English Acronym：

研究课题的正式科学名称：

应用胎盘提取热休克蛋白制剂治疗强直性脊柱炎、系统性红斑狼疮等自身免疫疾病的前导性临床研究

Scientific title：

A pilot clinical study of heat shock protein preparation extracted from placenta in the treatment of autoimmune diseases such as ankylosing spondylitis and systemic lupus erythematosus etc.

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：

孟颂东 

研究负责人：

周中华 

Applicant：

Meng Songdong 

Study leader：

Zhou Zhonghua 

申请注册联系人电话：

Applicant telephone：

+86 15810156005

研究负责人电话：

Study leader's telephone：

+86 15903732068

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：

mengsd@im.ac.cn

研究负责人电子邮件：

Study leader's E-mail：

15603731789@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：

广东省佛山市南海区桂城街道天富科技城

研究负责人通讯地址：

海南省琼海市博鳌旅游医疗先行区康祥路

Applicant address：

Tianfu Science and Technology City, Guicheng Street, Nanhai District, Foshan, Guangdong

Study leader's address：

Kangxiang Road, Boao tourism medical Pioneer Area, Qionghai, Hainan

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：

佛山热休生物技术有限公司

Applicant's institution：

Foshan Rexiu Biotechnology Co., Ltd.

研究负责人所在单位：

博鳌恒大国际医院

Affiliation of the Leader：

Boao Evergrande International Hospital

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：

BEIH20211112号

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：

博鳌恒大国际医院伦理委员会

Name of the ethic committee：

Ethics Committee of Boao Evergrande International Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2021-11-12 00:00:00

伦理委员会联系人：

和钢

Contact Name of the ethic committee：

He Gang

伦理委员会联系地址：

海南省琼海市博鳌旅游医疗先行区康祥路

Contact Address of the ethic committee：

Kangxiang Road, Boao tourism medical Pioneer Area, Qionghai, Hainan

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：

博鳌恒大国际医院

Primary sponsor：

Boao Evergrande International Hospital

研究实施负责（组长）单位地址：

海南省琼海市博鳌旅游医疗先行区康祥路

Primary sponsor's address：

Kangxiang Road, Boao tourism medical Pioneer Area, Qionghai, Hainan

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

广东

市(区县)：

佛山

Country：

China

Province：

Guangdong

City：

Foshan

单位(医院)：

佛山热休生物技术有限公司

具体地址：

南海区桂城街道天富科技城

Institution
hospital：

Foshan Rexiu Biotechnology Co., Ltd.

Address：

Tianfu Science and Technology City, Guicheng Street, Nanhai District

经费或物资来源：

自筹

Source(s) of funding：

Self-funded

Target disease：

Autoimmune diseases (ankylosing spondylitis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, erythroderma)

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：

0

研究设计：

单臂 

Study design：

Single arm 

研究目的：

通过本前导性单臂临床研究，获得应用胎盘提取热休克蛋白制剂治疗强直性脊柱炎、系统性红斑狼疮等自身免疫疾病的安全性数据和疗效数据。探索应用胎盘提取热休克蛋白制剂治疗强直性脊柱炎、系统性红斑狼疮等自身免疫疾病能提高调节性T细胞（Treg）的水平，降低滤泡辅助性T细胞（Tfh）的水平，以及治疗后身抗体的转阴情况。  

Objectives of Study：

Through this pilot single-arm clinical study, the safety data and efficacy data of placenta-extracted heat shock protein preparations in the treatment of autoimmune diseases such as ankylosing spondylitis and systemic lupus erythematosus were obtained. Exploring the application of placenta-extracted heat shock protein preparations in the treatment of autoimmune diseases such as ankylosing spondylitis and systemic lupus erythematosus can increase the level of regulatory T cells (Treg), reduce the level of follicular helper T cells (Tfh), and reduce the level of follicular helper T cells (Tfh) after treatment. Negative status of body antibodies.

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.强直性脊柱炎：
（1）年龄18-65周岁，性别不限；
（2）所有强直性脊柱炎入组患者均符合1984年修订的AS纽约标准。在筛选期和基线期被确诊为AS, 符合以下条件的2个：BASDAI评分≥4分；在疼痛视觉模拟量表（VAS） 中评估中，总背痛≥4分；
（3）晨僵时间≥1小时；
（3）所有强直性脊柱炎入组者HLA-B27均为阳性；
（4）所有强直性脊柱炎入组者均对1种以上的NSAIDs 或者1种以上DMARDs规范治疗无效或者不能耐受；
（5）患者需签署知情同意书；
2.系统性红斑狼疮：
（1）年龄18-65周岁，性别不限；
（2）所有系统性红斑狼疮入组者，根据系统性红斑狼疮国际协作组SLICC2012标准，满足其中4项标准，包括至少1项临床标准和1项免疫学标准；或肾活检证实狼疮肾炎，同时抗核抗体阳性或抗ds-DNA抗体阳性；
（3）所有系统性红斑狼疮患者中，SLEDAI评分≤14分的患者；
（4）患者需签署知情同意书；
3.类风湿性关节炎：
（1）年龄18-65周岁，性别不限；
（2）所有类风湿性关节炎入组患者均符合ACR/EULAR新标准(美国风湿病学会／欧洲风湿病防治联合会，2010)；
（3）类风湿性关节炎早期，症状明显（晨僵/痛或压痛）或相关检查指标阳性，有功能性损伤或轻微功损，无器质性、不可逆损伤；
（4）患者需签署知情同意书；
4.I型糖尿病：
（1）年龄≤40周岁，性别不限；
（2）第一诊断为1型糖尿病（不伴急性并发症 - 酮症酸中毒、低血糖昏迷、高渗性昏迷、乳酸酸中毒等）（ICD-10：E10.901）；
（3）符合《儿科学》（申昆玲等主编，人民卫生出版社，2016年，第1版）、《诸福棠实用儿科学（第8版）》（人民卫生出版社，2015）、《2018 ISPAD临床实践共识指南：儿童青少年糖尿病的定义，流行病学和分类》诊断标准；
（4）分型：免疫介导（ⅠA型）；
（5）患者需签署知情同意书；
5.红皮病:
（1）年龄18-65周岁，性别不限；
（2）符合《临床诊疗指南－皮肤病与性病分册》、《临床技术操作规范－皮肤病与性病分册》、《中国临床皮肤病学》第4版红皮病的诊断标准；
（3）以红皮病作为第一诊断；
（4）所需的主要病历资料齐全；
（5）患者需签署知情同意书。

Inclusion criteria

1. Ankylosing spondylitis:
(1) 18-65 years old, gender is not limited;
(2) All patients with ankylosing spondylitis met the AS New York criteria revised in 1984. AS was diagnosed at screening and baseline, and 2 of the following conditions were met: BASDAI score >= 4 points; total back pain >= 4 points as assessed on the visual analog scale (VAS) for pain;
(3) Morning stiffness time >= 1 hour;
(3) All patients with ankylosing spondylitis were positive for HLA-B27;
(4) All patients with ankylosing spondylitis were ineffective or could not tolerate standard treatment of more than one NSAIDs or more than one DMARDs;
(5) The patient needs to sign the informed consent;
2. Systemic lupus erythematosus:
(1) 18-65 years old, gender is not limited;
(2) All patients with systemic lupus erythematosus, according to the systemic lupus erythematosus International Collaborative Group SLICC2012 criteria, meet 4 criteria, including at least 1 clinical criteria and 1 immunological criteria; or renal biopsy confirmed lupus nephritis, and at the same time Antinuclear antibody positive or anti-ds-DNA antibody positive;
(3) Among all patients with systemic lupus erythematosus, the patients with SLEDAI score <=14 points;
(4) The patient needs to sign the informed consent;
3. Rheumatoid Arthritis:
(1) 18-65 years old, gender is not limited;
(2) All patients with rheumatoid arthritis met the new ACR/EULAR criteria (American College of Rheumatology/European Federation for the Prevention and Treatment of Rheumatism, 2010);
(3) In the early stage of rheumatoid arthritis, the symptoms are obvious (morning stiffness/pain or tenderness) or related test indicators are positive, there is functional damage or slight functional damage, and there is no organic or irreversible damage;
(4) The patient needs to sign the informed consent;
4. Type I diabetes:
(1) <= 40 years old, gender is not limited;
(2) The first diagnosis is type 1 diabetes mellitus (without acute complications - ketoacidosis, hypoglycemic coma, hyperosmolar coma, lactic acidosis, etc.) (ICD-10: E10.901);
(3) In line with "Pediatrics" (Shen Kunling et al. editor-in-chief, People's Health Publishing House, 2016, 1st edition), "Zhu Futang Practical Pediatrics (8th Edition)" (People's Health Publishing House, 2015), "2018" ISPAD Clinical Practice Consensus Guidelines: Definition, Epidemiology and Classification of Diabetes in Children and Adolescents" Diagnostic Criteria;
(4) Classification: immune-mediated (type IA);
(5) The patient needs to sign the informed consent;
5. Erythroderma:
(1) 18-65 years old, gender is not limited;
(2) Comply with the diagnostic criteria of "Clinical Diagnosis and Treatment Guidelines - Dermatology and Venereal Diseases", "Clinical Technical Operation Standard - Dermatology and Venereal Diseases", and "Chinese Clinical Dermatology" 4th Edition Erythroderma;
(3) Take erythroderma as the first diagnosis;
(4) The main medical records required are complete;
(5) Patients need to sign the informed consent.

排除标准：

1.强直性脊柱炎：
（1）脊柱关节完全融合者；
（2）对任何用药成分（蛋白质成分）过敏者；
（3）接受治疗前4 w内有关节或脊柱手术经历的患者；
（4）治疗前24 w内有应用生物制剂经历的患者；
（5）治疗前24 w 内有应用其他药物如沙利度胺的患者；
（6）哺乳期妇女；
（7）艾滋病（acquired immune deficiency syndrome, AIDS ）患者、人免疫缺陷病毒（human immunodeficiency virus, HIV）抗体、梅毒螺旋抗体、丙肝抗体（HCV-Ab）、乙肝表面抗原（HBV-Ag）任何一项阳性；
（8）有肿瘤病史；（9）活动性结核或结核病史， 筛选期胸影像学有既往结核病灶、结核菌素(purified protein derivative, PPD)、 γ干扰素释放结核感染T细胞斑点试验(TSPOT)阳性；
（10）除AS以外的其他自身免疫性疾病，如系统性红斑狼疮(systemic lupus erythematosus, SLE)、类风湿关节炎(rheumatoid arthritis, RA)等；
（11）泌尿系或呼吸道等有急慢性炎症；
（12）有严重的重要器官慢性病病史；
（13）存在药物或酒精滥用，存在可能会干扰患者参与研究或影响研究结果评价的医疗、心理或社会状况；
（14）存在精神障碍者；
（15）筛选前90天内参加过或正在参加其他药物或医疗器械临床试验者；
（16）因各种原因不能接受血液或体液等标本采集，临床检查或影像学检查者；
（17）经研究者评定，存在其他不适于参加本研究的因素者；
2.系统性红斑狼疮：
（1）筛选时患有严重狼疮性肾炎者（24小时蛋白定量＞6g，或血肌酐＞2.5mg/dL或221μmol/L），或患有活动性肾病需要紧急治疗，或需要血液透析、或大剂量糖皮质激素（泼尼松或其等效价药物，剂量＞100mg/天）治疗者；
（2）筛选时患有活动性中枢神经系统性（CNS）红斑狼疮（包括癫痫、精神失常、脑器质性病变、脑血管意外（CVA）、或中枢神经系统血管炎），而需要干预治疗者；
（3） 筛选时患有严重狼疮性肺部损害（包括肺动脉高压、肺出血、肺梗死、肺萎缩、肺间质纤维化等）；
（4）筛选时患有严重狼疮性心脏损害（包括冠状动脉血管受累、Libman-Sacks心内膜炎、心肌炎、心包填塞和恶性高血压等）；
（5）既往或现有与SLE无关的、临床症状显著不稳定或不可控的急慢性疾病者（如：心脑血管疾病、肺部疾病、血液疾病、胃肠道疾病、肝脏疾病、肾病、神经疾病、恶性肿瘤或感染性疾病），研究者认为这些疾病对试验结果可能具有混淆作用、或对患者存在不可预测的风险；
（6） 感染：受试者存在需要治疗的急性或慢性感染（如肺结核、肺囊虫、单纯疱疹病毒、带状疱疹、巨细胞病毒和非典型分枝杆菌等）；
（7） 既往进行过主要器官（如：心、肝、肺、肾）或造血干细胞/骨髓移植者；
（8）近5年内有恶性肿瘤病史者；
（9） 15个月内有手术计划者；
（10） 存在药物或酒精滥用，存在可能会干扰患者参与研究或影响研究结果评价的医疗、心理或社会状况；
（11）存在精神障碍者；
（12）筛选前90天内参加过或正在参加其他药物或医疗器械临床试验者；
（13） 妊娠和哺乳期女性，或不愿采取避孕措施计划生育者；
（14）HIV：有HIV检测阳性的病史，或筛选时HIV检测结果阳性；
（15）因各种原因不能接受血液或体液等标本采集，临床检查或影像学检查者；
（16）经研究者评定，存在其他不适于参加本研究的因素者；
3.类风湿性关节炎：
（1）类风湿性关节炎合并并发症（如心、肾、肺等）、基础状态差、畸形严重或其他疾病需要临床系统性治疗的；
（2）关节完全融合者；（3）对任何用药成分（蛋白质）过敏者；
（4）接受治疗前4 w内有关节或脊柱手术经历的患者；
（5）治疗前24 w内有应用生物制剂经历的患者；
（6）孕期、哺乳期妇女；（7）艾滋病（acquired immune deficiency syndrome, AIDS ）患者、人免疫缺陷病毒（human immunodeficiency virus, HIV）抗体、梅毒螺旋抗体、丙肝抗体（HCV-Ab）、乙肝表面抗原（HBV-Ag）任何一项阳性；
（8）有肿瘤病史；
（9）活动性结核或结核病史， 筛选期胸影像学有既往结核病灶、结核菌素(purified protein derivative, PPD)、 γ干扰素释放结核感染T细胞斑点试验(TSPOT)阳性；
（10）除RA以外的其他自身免疫性疾病，如系统性红斑狼疮(systemic lupus erythematosus, SLE)、强直性脊柱炎(AS)等；
（11）泌尿系或呼吸道等有急慢性炎症；
（12）有严重的重要器官慢性病病史；
（13）存在药物或酒精滥用，存在可能会干扰患者参与研究或影响研究结果评价的医疗、心理或社会状况；
（14）存在精神障碍者；
（15）筛选前90天内参加过或正在参加其他药物或医疗器械临床试验者；
（16）因各种原因不能接受血液或体液等标本采集，临床检查或影像学检查者；
（17）经研究者评定，存在其他不适于参加本研究的因素者；
4.I型糖尿病：
（1）1型糖尿病合并急性并发症者（酮症酸中毒、低血糖昏迷、高渗性昏迷、乳酸酸中毒等）或其他严重性疾病需要临床系统性治疗的；
（2）出现严重的糖尿病慢性并发症（糖尿病肾病、眼部、心血管、神经系统并发症、皮肤病变、糖尿病足）；
（3）分型为特发性（ⅠB型）；
（4）对任何用药成分（蛋白质成分）过敏者；
（5）治疗前24 w内有应用生物制剂经历的患者；
（6）感染：受试者存在需要治疗的急性或慢性感染（如肺结核、肺囊虫、单纯疱疹病毒、带状疱疹、巨细胞病毒和非典型分枝杆菌等）；
（7）既往进行过主要器官（如：心、肝、肺、肾）或造血干细胞/骨髓移植者；
（8）近5年内有恶性肿瘤病史者；
（9）15个月内有手术计划者；
（10）存在药物或酒精滥用，存在可能会干扰患者参与研究或影响研究结果评价的医疗、心理或社会状况；
（11）存在精神障碍者；
（12）筛选前90天内参加过或正在参加其他药物或医疗器械临床试验者；
（13）妊娠和哺乳期女性，或不愿采取避孕措施计划生育者；
（14）HIV：有HIV检测阳性的病史，或筛选时HIV检测结果阳性；
（15）因各种原因不能接受血液或体液等标本采集，临床检查或影像学检查者；
（16）经研究者评定，存在其他不适于参加本研究的因素者；
5.红皮病：
（1）感染：受试者存在需要治疗的急性或慢性感染（如肺结核、肺囊虫、单 纯疱疹病毒、带状疱疹、巨细胞病毒和非典型分枝杆菌等）；
（2）对任何用药成分（蛋白质成分）过敏者；
（3）既往进行过主要器官（如：心、肝、肺、肾）或造血干细胞/骨髓移植者；
（4）15个月内有手术计划者；
（5）存在药物或酒精滥用，存在可能会干扰患者参与研究或影响研究结果评价的医疗、心理或社会状况；
（6）存在精神障碍者；
（7）筛选前90天内参加过或正在参加其他药物或医疗器械临床试验者；
（8）妊娠和哺乳期女性，或不愿采取避孕措施计划生育者；
（9） 因各种原因不能接受血液或体液等标本采集，临床检查或影像学检查者；
（10）有严重的重要器官慢性病病史；
（11）经研究者评定，存在其他不适于参加本研究的因素者。

Exclusion criteria：

1. Ankylosing spondylitis:
(1) Complete fusion of spinal joints;
(2) Those who are allergic to any drug ingredient (protein ingredient);
(3) Patients with joint or spine surgery experience within 4 weeks before receiving treatment;
(4) Patients who have experienced the application of biological agents within 24 weeks before treatment;
(5) Patients who have used other drugs such as thalidomide within 24 weeks before treatment;
(6) Lactating women;
(7) AIDS (acquired immune deficiency syndrome, AIDS) patients, human immunodeficiency virus (human immunodeficiency virus, HIV) antibody, syphilis helix antibody, hepatitis C antibody (HCV-Ab), hepatitis B surface antigen (HBV-Ag) any one positive;
(8) have a history of tumor; (9) a history of active tuberculosis or tuberculosis, and chest imaging in the screening period has past tuberculosis lesions, tuberculin (purified protein derivative, PPD), gamma interferon-releasing tuberculosis infection T cell spot test (TSPOT) )positive;
(10) Other autoimmune diseases other than AS, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), etc.;
(11) Acute and chronic inflammation of the urinary system or respiratory tract;
(12) Have a history of serious chronic diseases of vital organs;
(13) There is drug or alcohol abuse, and there are medical, psychological or social conditions that may interfere with the patients participation in research or affect the evaluation of research results;
(14) Persons with mental disorders;
(15) Those who have participated in or are participating in clinical trials of other drugs or medical devices within 90 days before screening;
(16) Those who cannot accept the collection of blood or body fluids and other specimens, clinical examination or imaging examination for various reasons;
(17) Those who have other factors that are not suitable for participating in this study as assessed by the investigator;
2. Systemic lupus erythematosus:
(1) Patients with severe lupus nephritis at screening (24-hour protein quantification >6g, or serum creatinine >2.5mg/dL or 221μmol/L), or active renal disease requiring emergency treatment, or requiring hemodialysis, or Patients treated with high-dose glucocorticoids (prednisone or its equivalent, dose >100 mg/day);
(2) Suffering from active central nervous system (CNS) lupus erythematosus (including epilepsy, mental disorders, organic brain lesions, cerebrovascular accident (CVA), or central nervous system vasculitis) at the time of screening and requiring intervention therapy By;
(3) Severe lupus lung damage (including pulmonary hypertension, pulmonary hemorrhage, pulmonary infarction, pulmonary atrophy, pulmonary fibrosis, etc.) at the time of screening;
(4) Severe lupus heart damage (including coronary vascular involvement, Libman-Sacks endocarditis, myocarditis, cardiac tamponade and malignant hypertension, etc.) at the time of screening;
(5) Patients with previous or existing acute and chronic diseases unrelated to SLE, with significantly unstable or uncontrollable clinical symptoms (such as: cardiovascular and cerebrovascular diseases, lung diseases, blood diseases, gastrointestinal diseases, liver diseases, kidney diseases, neurological disease, malignancy, or infectious disease), which the investigator believes may confound trial results or present unpredictable risks to patients;
(6) Infection: The subject has acute or chronic infection requiring treatment (such as tuberculosis, Pneumocystis, herpes simplex virus, herpes zoster, cytomegalovirus and atypical mycobacteria, etc.);
(7) Those who have undergone major organ (such as: heart, liver, lung, kidney) or hematopoietic stem cell/bone marrow transplantation in the past;
(8) Those who have a history of malignant tumor within the past 5 years;
(9) Those who have an operation plan within 15 months;
(10) There is drug or alcohol abuse, and there are medical, psychological or social conditions that may interfere with the patient's participation in the study or affect the evaluation of the study results;
(11) Persons with mental disorders;
(12) Those who have participated in or are participating in clinical trials of other drugs or medical devices within 90 days before screening;
(13) Pregnant and lactating women, or those who are unwilling to take contraceptive measures for family planning;
(14) HIV: a history of positive HIV test, or a positive HIV test result at screening;
(15) Those who cannot accept the collection of blood or body fluids and other specimens, clinical examination or imaging examination for various reasons;
(16) Those who have other factors that are not suitable for participating in this study as assessed by the investigator;
3. Rheumatoid Arthritis:
(1) Rheumatoid arthritis complicated by complications (such as heart, kidney, lung, etc.), poor basic state, severe deformity, or other diseases that require clinical systemic treatment;
(2) Those with complete joint fusion; (3) Those who are allergic to any drug ingredient (protein);
(4) Patients with joint or spine surgery experience within 4 weeks before receiving treatment;
(5) Patients who have experienced the application of biological agents within 24 weeks before treatment;
(6) Pregnant and lactating women; (7) AIDS (acquired immune deficiency syndrome, AIDS) patients, human immunodeficiency virus (HIV) antibody, syphilis helix antibody, hepatitis C antibody (HCV-Ab), hepatitis B surface Any one of the antigens (HBV-Ag) is positive;
(8) have a history of tumor;
(9) History of active tuberculosis or tuberculosis, and chest imaging in the screening period has past tuberculosis lesions, tuberculin (purified protein derivative, PPD), and interferon-gamma-releasing tuberculosis infection T cell spot test (TSPOT) positive;
(10) Other autoimmune diseases other than RA, such as systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), etc.;
(11) Acute and chronic inflammation of the urinary system or respiratory tract;
(12) Have a history of serious chronic diseases of vital organs;
(13) There is drug or alcohol abuse, and there are medical, psychological or social conditions that may interfere with the patients participation in research or affect the evaluation of research results;
(14) Persons with mental disorders;
(15) Those who have participated in or are participating in clinical trials of other drugs or medical devices within 90 days before screening;
(16) Those who cannot accept the collection of blood or body fluids and other specimens, clinical examination or imaging examination for various reasons; (17) Those who have other factors that are not suitable for participating in this study as assessed by the investigator;
4. Type I diabetes:
(1) Type 1 diabetes patients with acute complications (ketoacidosis, hypoglycemic coma, hyperosmolar coma, lactic acidosis, etc.) or other serious diseases requiring clinical systemic treatment;
(2) Serious chronic complications of diabetes (diabetic nephropathy, eye, cardiovascular, nervous system complications, skin lesions, diabetic foot);
(3) The classification is idiopathic (type IB);
(4) Those who are allergic to any drug ingredient (protein ingredient);
(5) Patients who have experienced the application of biological agents within 24 weeks before treatment;
(6) Infection: The subject has acute or chronic infection requiring treatment (such as tuberculosis, Pneumocystis, herpes simplex virus, herpes zoster, cytomegalovirus and atypical mycobacteria, etc.);
(7) Those who have undergone major organ (such as heart, liver, lung, kidney) or hematopoietic stem cell/bone marrow transplantation in the past;
(8) Those who have a history of malignant tumor within the past 5 years;
(9) Those who have an operation plan within 15 months;
(10) There is drug or alcohol abuse, and there are medical, psychological or social conditions that may interfere with the patient's participation in the study or affect the evaluation of the study results;
(11) Persons with mental disorders;
(12) Those who have participated in or are participating in clinical trials of other drugs or medical devices within 90 days before screening;
(13) Pregnant and lactating women, or those who are unwilling to take contraceptive measures for family planning;
(14) HIV: a history of positive HIV test, or a positive HIV test result at screening;
(15) Those who cannot accept blood or body fluid specimen collection, clinical examination or imaging examination due to various reasons;
(16) Those who have other factors that are not suitable for participating in this study as assessed by the investigator;
5. Erythroderma:
(1) Infection: The subject has acute or chronic infection requiring treatment (such as tuberculosis, Pneumocystis, herpes simplex virus, herpes zoster, cytomegalovirus and atypical mycobacteria, etc.);
(2) Those who are allergic to any drug ingredient (protein ingredient);
(3) Those who have undergone major organ (such as heart, liver, lung, kidney) or hematopoietic stem cell/bone marrow transplantation in the past;
(4) Those who have an operation plan within 15 months;
(5) There is drug or alcohol abuse, and there are medical, psychological or social conditions that may interfere with the patient's participation in the study or affect the evaluation of the study results;
(6) Persons with mental disorders;
(7) Those who have participated in or are participating in clinical trials of other drugs or medical devices within 90 days before screening;
(8) Pregnant and lactating women, or those who are unwilling to take contraceptive measures for family planning;
(9) Those who cannot accept blood or body fluid specimen collection, clinical examination or imaging examination due to various reasons;
(10) Have a history of serious chronic diseases of vital organs;
(11) Those who have other factors that are not suitable for participating in this study as assessed by the researchers.

研究实施时间：

Study execute time：

从 From 2021-12-10 00:00:00至 To 2023-09-09 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2021-12-10 00:00:00 至 To 2022-06-09 00:00:00  

干预措施：

Interventions：

组别：

治疗组

样本量：

10

Group：

Treatment Group

Sample size：

干预措施：

胎盘提取热休克蛋白制剂治疗

干预措施代码：

Intervention：

Treatment of heat shock protein preparation extracted from placenta

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 海南 

市(区县)：

 琼海 

Country：

China 

Province：

Hainan 

City：

Qionghai 

单位(医院)：

博鳌恒大国际医院 

单位级别：

三级甲等 

Institution
hospital：

Boao Evergrande International Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

安全性评价指标

指标类型：

主要指标

Outcome：

Safety evaluation index

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

疗效评价指标

指标类型：

主要指标

Outcome：

Efficacy evaluation index

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

免疫学指标

指标类型：

次要指标

Outcome：

Immunological index

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：

标本中文名：

尿液

组织：

Sample Name：

Urine

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 65 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）：

前导性、前瞻、单臂、单中心

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

Pilot,prospective,single arms,single center

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：

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

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）：

博鳌恒大国际医院

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

Boao Evergrande International Hospital

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：

研究者将收集到的患者数据填写到指定的病例报告表（CRF）。

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

The researchers will fill the collected patient data into the designated case report form (CRF).

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：

  2021-12-07 05:20:16