Today is 2020-06-06

Multi-center, randomized, double-blind, parallel, positive drug control, comparison of domestic recombinant anti-TNF-α whole-human monoclonal antibody injection (HS016) and original drug Xiulai? subcutaneous injection for active ankylosing spondylitis Phase III clinical trials for efficacy and safety
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注册号:

Registration number:

ChiCTR1900022520 

最近更新日期:

Date of Last Refreshed on:

2019-09-16 

注册时间:

Date of Registration:

2019-04-15 

注册号状态:

补注册  

Registration Status:

Retrospective registration  

注册题目:

多中心、随机、双盲、平行、阳性药对照,比较国产重组抗肿瘤坏死因子-α 全人源单克隆抗体注射液(HS016)和原研药修美乐皮下注射治疗活动性强直性脊柱炎有效性和安全性的III期临床试验 

Public title:

Multi-center, randomized, double-blind, parallel, positive drug control, comparison of domestic recombinant anti-TNF-α whole-human monoclonal antibody injection (HS016) and original drug Xiulai? subcutaneous injection for active ankylosing spondylitis Phase III clinical trials for efficacy and safety 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

多中心、随机、双盲、平行、阳性药对照,比较国产重组抗肿瘤坏死因子-α 全人源单克隆抗体注射液(HS016)和原研药修美乐皮下注射治疗活动性强直性脊柱炎有效性和安全性的III期临床试验 

Scientific title:

Multi-center, randomized, double-blind, parallel, positive drug control, comparison of domestic recombinant anti-TNF-α whole-human monoclonal antibody injection (HS016) and original drug Xiulai? subcutaneous injection for active ankylosing spondylitis Phase III clinical trials for efficacy and safety 

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:

高晨燕 

研究负责人:

曾小峰 

Applicant:

Chenyan Gao 

Study leader:

Xiaofeng Zeng 

申请注册联系人电话:

Applicant telephone:

+86 18858543313 

研究负责人电话:

Study leader's telephone:

+86 13501069845 

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:

chygao@hisunpharm.com 

研究负责人电子邮件:

Study leader's E-mail:

xiaofeng_zeng@cstar.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:

海市徐汇区枫林路381号 

研究负责人通讯地址:

北京市东城区帅府园1号 

Applicant address:

381 Fenglin Road, Xuhui District, Shanghai 

Study leader's address:

1 Shuaifuyuan, Dongcheng District, Beijing 

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:

上海百盈医药科技有限公司/浙江海正药业股份有限公司 

Applicant's institution:

Bio-Inno. Med Co., Ltd/ Zhejiang Hisun Pharmaceutical CO.,LTD 

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:

HS2016038 

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:

中国医学科学院北京协和医院药物临床试验伦理委员会 

Name of the ethic committee:

Ethics Committee for Clinical Drug Trials, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences 

伦理委员会批准日期:

Date of approved by ethic committee:

2016-05-18 

伦理委员会联系人:

姜楠 

Contact Name of the ethic committee:

Nan Jiang 

伦理委员会联系地址:

北京市东城区帅府园1号 

Contact Address of the ethic committee:

1 Shuaifuyuan, Dongcheng District, Beijing 

伦理委员会联系人电话:

Contact phone of the ethic committee:

+86 13651769963 

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:

中国医学科学院北京协和医院 

Primary sponsor:

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences 

研究实施负责(组长)单位地址:

北京市东城区帅府园一号 

Primary sponsor's address:

1 Shuaifuyuan, Dongcheng District, Beijing 

试验主办单位(项目批准或申办者):

Secondary sponsor:

国家:

中国

省(直辖市):

北京

市(区县):

Country:

China

Province:

Beijing

City:

单位(医院):

北京大学第一医院

具体地址:

西城区西什库大街8号

Institution
hospital:

Peking University First Hospital

Address:

8 Xishiku Street, Xicheng District

国家:

中国

省(直辖市):

北京

市(区县):

Country:

China

Province:

Beijing

City:

单位(医院):

北京大学第三医院

具体地址:

海淀区花园北路49号

Institution
hospital:

Peking University Third Hospital

Address:

49 Huayuan Road North, Haidian District

国家:

中国

省(直辖市):

北京

市(区县):

Country:

China

Province:

Beijing

City:

单位(医院):

中日友好医院

具体地址:

朝阳区樱花园东街2号

Institution
hospital:

Sino-Japanese Friendship Hospital

Address:

2 Yinghuayuan Street East, Chaoyang District

国家:

中国

省(直辖市):

北京

市(区县):

Country:

China

Province:

Beijing

City:

单位(医院):

北京医院

具体地址:

东城区东单大华路1号

Institution
hospital:

Beijing Hospital

Address:

1 Dongdan Dahua Road, Dongcheng District

国家:

中国

省(直辖市):

山西省

市(区县):

太原

Country:

China

Province:

Shanxi

City:

Taiyuan

单位(医院):

山西医科大学第二医院

具体地址:

五一路382号

Institution
hospital:

Second Hospital of Shanxi Medical University

Address:

382 Wuyi Road

国家:

中国

省(直辖市):

山西省

市(区县):

太原市

Country:

China

Province:

Shanxi

City:

Taiyuan

单位(医院):

山西医科大学第一医院

具体地址:

迎泽区解放南路85号

Institution
hospital:

The First Hospital of Shanxi Medical University

Address:

85 Jiefang Road South, Yingze District

国家:

中国

省(直辖市):

河北省

市(区县):

石家庄

Country:

China

Province:

Hebei Province

City:

Shijiazhuang

单位(医院):

河北医科大学第三医院

具体地址:

自强路139号

Institution
hospital:

The Third Hospital of Hebei Medical University

Address:

139 Ziqiang Road

国家:

中国

省(直辖市):

天津市

市(区县):

Country:

China

Province:

Tianjin

City:

单位(医院):

天津医科大学总医院

具体地址:

和平区鞍山道154号

Institution
hospital:

Tianjin Medical University General Hospital

Address:

154 Anshan Road, Heping District

国家:

中国

省(直辖市):

陕西省

市(区县):

西安市

Country:

China

Province:

Shaanxi Province

City:

Xi'an

单位(医院):

西安交通大学第一附属医院

具体地址:

雁塔西路277号

Institution
hospital:

First Affiliated Hospital of Xi'an Jiaotong University

Address:

277 Yanta Road West

国家:

中国

省(直辖市):

安徽省

市(区县):

合肥市

Country:

China

Province:

Anhui Province

City:

Hefei

单位(医院):

安徽医科大学第一附属医院

具体地址:

蜀山区绩溪路218号

Institution
hospital:

The First Affiliated Hospital of Anhui Medical University

Address:

218 Jixi Road, Shushan District

国家:

中国

省(直辖市):

江苏省

市(区县):

南京

Country:

China

Province:

Jiangsu Province

City:

Nanjing

单位(医院):

江苏省人民医院

具体地址:

鼓楼区广州路300号

Institution
hospital:

Jiangsu Provincial People's Hospital

Address:

300 Guangzhou Road, Gulou District

国家:

中国

省(直辖市):

上海市

市(区县):

Country:

China

Province:

Shanghai

City:

单位(医院):

复旦大学学附属中山医院

具体地址:

徐汇区枫林路180号

Institution
hospital:

Zhongshan Hospital, Fudan University

Address:

180 Fenglin Road, Xuhui District

国家:

中国

省(直辖市):

上海市

市(区县):

Country:

China

Province:

Shanghai

City:

单位(医院):

复旦大学附属华山医院

具体地址:

静安区乌鲁木齐中路12号

Institution
hospital:

Huashan Hospital affiliated to Fudan University

Address:

12 Middle Urumqi Road, Jing'an District

国家:

中国

省(直辖市):

上海市

市(区县):

Country:

China

Province:

Shanghai

City:

单位(医院):

上海长海医院

具体地址:

杨浦区长海路168号

Institution
hospital:

Shanghai Changhai Hospital

Address:

168 Changhai Road, Yangpu District

国家:

中国

省(直辖市):

上海市

市(区县):

Country:

China

Province:

Shanghai

City:

单位(医院):

上海市光华中西医结合医院

具体地址:

长宁区新华路540号

Institution
hospital:

Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine

Address:

540 Xinhua Road, Changning District

国家:

中国

省(直辖市):

湖南省

市(区县):

长沙市

Country:

China

Province:

Hunan

City:

Changsha

单位(医院):

中南大学湘雅医院

具体地址:

湘雅路87号

Institution
hospital:

Xiangya Hospital, Central South University

Address:

87 Xiangya Road

国家:

中国

省(直辖市):

湖南省

市(区县):

长沙市

Country:

China

Province:

Hu'nan

City:

Changsha

单位(医院):

中南大学湘雅二医院

具体地址:

人民中路139号

Institution
hospital:

The Second Xiangya Hospital of Central South University

Address:

139 Middle Renmin Road

国家:

中国

省(直辖市):

湖南省

市(区县):

株洲市

Country:

China

Province:

Hu'nan

City:

Zhuzhou

单位(医院):

株洲市中心医院

具体地址:

天元区长江南路116号

Institution
hospital:

Zhuzhou Central Hospital

Address:

116 Changjiang Road South, Tianyuan District

国家:

中国

省(直辖市):

浙江省

市(区县):

杭州市

Country:

China

Province:

Zhejiang

City:

Hangzhou

单位(医院):

浙江大学医学院附属第二医院

具体地址:

上城区解放路88号

Institution
hospital:

The Second Affiliated Hospital Zhejiang University School of Medicine

Address:

88 Jiefang Road, Shangcheng District

国家:

中国

省(直辖市):

四川省

市(区县):

成都市

Country:

China

Province:

Sichuan

City:

Chengdu

单位(医院):

四川大学华西医院

具体地址:

武侯区国学巷37号

Institution
hospital:

West China Hospital, Sichuan University

Address:

37 Guoxue Lane, Wuhou District

国家:

中国

省(直辖市):

云南省

市(区县):

昆明

Country:

China

Province:

Yunnan Province

City:

Kunming

单位(医院):

昆明医科大学第一附属医院

具体地址:

五华区西昌路295号

Institution
hospital:

First Affiliated Hospital of Kunming Medical University

Address:

295 Xichang Road, Wuhua District

国家:

中国

省(直辖市):

黑龙江省

市(区县):

哈尔滨市

Country:

China

Province:

Heilongjiang

City:

Harbin

单位(医院):

哈尔滨医科大学附属第一医院

具体地址:

南岗区大直街199号

Institution
hospital:

The First Affiliated Hospital of Harbin Medical University

Address:

199 Dazhi Street, Nangang District

国家:

中国

省(直辖市):

湖北省

市(区县):

武汉市

Country:

China

Province:

Hubei

City:

Wuhan

单位(医院):

华中科技大学同济医学院附属同济医院

具体地址:

解放大道1095号

Institution
hospital:

Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology

Address:

1095 Jiefang Avenue

国家:

中国

省(直辖市):

山东省

市(区县):

济南市

Country:

China

Province:

Shandong

City:

Ji'nan

单位(医院):

山东大学齐鲁医院

具体地址:

文化西路107号

Institution
hospital:

Qilu Hospital of Shandong University

Address:

107 Wenhua Road West

国家:

中国

省(直辖市):

湖北省

市(区县):

武汉市

Country:

China

Province:

Hubei Province

City:

Wuhan

单位(医院):

华中科技大学同济医学院附属协和医院

具体地址:

江汉区解放大道1277号

Institution
hospital:

Union Hospital of Tongji Medical College, Huazhong University of Science and Technology

Address:

1277 Jiefang Avenue, Jianghan District

国家:

中国

省(直辖市):

广东省

市(区县):

广州市

Country:

China

Province:

Guangdong Province

City:

Guangzhou

单位(医院):

广东省第二人民医院

具体地址:

海珠区新港中路466号

Institution
hospital:

Guangdong Second People's Hospital

Address:

466 Middle Xingang Road, Haizhu District

经费或物资来源:

浙江海正药业股份有限公司 

Source(s) of funding:

Zhejiang Hisun Pharmaceutical CO.,LTD 

研究疾病:

强直性脊柱炎 

Target disease:

Ankylosing spondylitis 

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:

III期临床试验 

Study phase:

研究目的:

主要目的: 比较24 周(每2 周一次)皮下注射国产重组抗肿瘤坏死因子-α全人源单克隆抗体注射液(HS016)和原研药修美乐治疗强直性脊柱炎(AS)受试者的有效性; 次要目的: 1)比较国产重组抗肿瘤坏死因子-α全人源单克隆抗体注射液(HS016)和原研药修美乐治疗强直性脊柱炎(AS)受试者的安全性和免疫原性; 2)评价国产重组抗肿瘤坏死因子-α全人源单克隆抗体注射液(HS016)和原研药修美乐治疗强直性脊柱炎(AS)受试者达稳态后给药间隔内血药浓度-时间曲线下面积(AUC?)和稳态时最高血药浓度(Cmax、ss)的生物等效性; 3)比较国产重组抗肿瘤坏死因子-α全人源单克隆抗体注射液(HS016)和原研药修美乐治疗强直性脊柱炎(AS)受试者的药代动力学特征。 

Objectives of Study:

Main objective: Comparison of 24 weeks (every 2 weeks) subcutaneously domestic recombination anti-tumor necrosis factor alpha total anthropogenic monoclonal antibody injection (HS016) and the original drug fix merlot effectiveness for the treatment of ankylosing spondylitis (AS) patients. Secondary objectives: 1) Comparison of the safety and immunogenicity of domestic recombinant anti-tumor necrosis factor-α whole human monoclonal antibody injection (HS016) and original drug Xiulai in the treatment of ankylosing spondylitis (AS) subjects; 2) Evaluation of domestic recombinant anti-tumor necrosis factor-α whole-human monoclonal antibody injection (HS016) and original research drug Xierule for treatment of ankylosing spondylitis (AS) subjects after steady-state administration of blood in the interval Bioequivalence of the area under the concentration-time curve (AUC?) and the highest plasma concentration (Cmax, ss) at steady state; 3) Comparison of the pharmacokinetic characteristics of domestic recombinant anti-tumor necrosis factor-α whole human monoclonal antibody injection (HS016) and original drug Xiulai in the treatment of ankylosing spondylitis (AS) subjects. 

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. 自愿签署知情同意书,能够依从方案并有能力进行相关程序者; 2. 年龄≥18岁且≤65周岁(以签署知情同意书当天为准); 3. 体重指数(BMI)在20~28 kg/m2之间(含20 kg/m2和28kg/m2),且体重在50~85kg之间者(含50kg和85kg); 4. 根据1984 年修订的强直性脊柱炎纽约标准,符合强直性脊柱炎的诊断者; 5. 在筛选期和基线期被确诊为活动性强直性脊柱炎(AS)者;其定义是至少符合下列条件中的2 个: 1)BASDAI 评分≥4; 2)在疼痛的视觉模拟量表(VAS)评估中,总背痛VAS≥4cm; 3)晨僵时间≥1 小时; 6. ≥1 种的非甾体类抗炎药(NSAIDs),或≥1 种的缓解病情的抗风湿药物(DMARDs)规范治疗≥4 周,但无效或不能耐受者。 7. 育龄期妇女在筛选和基线时,人绒毛膜促性腺激素(HCG)阴性。无生育能力的妇女(已行子宫切除或者双侧卵巢切除的妇女),或者处于绝经状态(定义为过去5 年内没有月经),可免除本要求。 8. 育龄妇女和男性受试者同意并承诺在整个试验期间(从签署知情同意书开始到末次访视),以及最后一次试验用药品给药后至少20周内使用有效的避孕措施。 

Inclusion criteria

1. Voluntary signing of informed consent, able to comply with the program and have the ability to carry out relevant procedures 2. Aged 18 to 65 years (The date of signing the informed consent shall prevail); 3. The body mass index (BMI) is between 20 and 28 kg/m2 (including 20 kg/m2 and 28 kg/m2), and the body weight is between 50 and 85 kg (including 50 kg and 85 kg); 4. According to the New York standard for ankylosing spondylitis revised in 1984, the diagnosis of ankylosing spondylitis; 5. Patients diagnosed with active ankylosing spondylitis (AS) during the screening and baseline periods; defined as at least 2 of the following: 1) BASDAI score >= 4; 2) In the assessment of pain visual analog scale (VAS), the total back pain VAS >= 4cm; 3) Morning stiffness time >= 1 hour; 6. >= 1 non-steroidal anti-inflammatory drugs (NSAIDs), or >= 1 remission of anti-rheumatic drugs (DMARDs) for treatment >= 4 weeks, but ineffective or intolerant; 7. Women of childbearing age are negative for human chorionic gonadotropin (HCG) at screening and baseline. Non-fertility women (women who have undergone hysterectomy or bilateral oophorectomy), or menopausal (defined as no menstruation in the past 5 years), are exempt from this requirement; 8. Women of childbearing age and male subjects agree and undertake to use effective contraceptive measures throughout the trial period (from the signing of informed consent to the last visit) and at least 20 weeks after the last trial drug administration. 

排除标准:

1. 脊柱完全僵直(融合)者; 2. 随机前24周内接受过脊柱手术或关节手术者; 3. 对任何试验用药品成分过敏者; 4. 既往使用过TNF拮抗剂治疗AS,且无效或不能耐受者; 5. 随机前12周内接受过包含TNF拮抗剂在内的其他TNF-α的抑制剂或其他生物制剂者,例如依那西普、英夫利昔单抗和阿达木单抗等;化学药物如沙利度胺等; 6. 抗药抗体(HAHAs)中心实验室结果阳性者; 7. 随机前8周内使用过 DMARDs类药品者(MTX和SSZ除外); 8. 随机前8周内使用过任何免疫调节制剂者; 9. 随机前4周内,服用柳氮磺吡啶(SSZ)>2g/日、或甲氨蝶呤(MTX)>15mg/周者; 10. 随机前4周内,虽然服用柳氮磺吡啶(SSZ)≤2g/日或甲氨蝶呤(MTX)≤15mg/周,但剂量发生改变者; 11. 随机前4周内,使用了阿片类镇痛药(曲马多除外)者; 12. 随机前4周内,使用NSAIDs或镇痛药剂量发生改变者; 13. 随机前4周内,使用2种或2种以上NSAIDs类药品者; 14. 随机前8周内使用中草药治疗者; 15. 随机前8周内使用活(减毒)疫苗者,已知将在试验期间会接受活(减毒)疫苗者; 16. 随机前16 周内接受关节内注射、脊柱或椎旁注射皮质类固醇类药物治疗者; 17. 严重的伴发疾病者,包括: 1) 未控制高血压(限定为筛选期收缩压>140mmHg,或筛选期舒张压>90mmHg); 2) 签署知情同意书前12 个月内出现心肌梗塞; 3) 不稳定型心绞痛; 4) 充血性心力衰竭; 5) 需要住院治疗或吸氧治疗的严重肺病,慢性支气管炎、阻塞性肺疾病; 6) 未控制的糖尿病; 7) 除AS 外任何炎症性疾病或免疫疾病,包括但不限于免疫缺陷综合征,如Felty 综合征;类风湿关节炎;系统性红斑狼疮;硬皮病或多肌炎;具有强直性脊柱炎关节外不稳定临床表现,例如银屑病、葡萄膜炎、溃疡性结肠炎等;多发性硬化症或其它中枢性脱髓鞘疾病;原发干燥综合症。 8) 合并慢性肝病; 9) 癌症或者癌症病史(已切除的皮肤基底细胞癌或鳞状细胞癌除外); 10) 开放的皮肤溃疡; 11) 签署知情同意书前4 周内合并感染,并需使用抗感染治疗; 12) 有活动性结核病或结核病史,或者胸部X 线片检查提示既往感染结核,或者 γ干扰素释放试验阳性; 13) 人类免疫缺陷病毒(HIV)抗体、梅毒螺旋体抗体、丙型肝炎病毒抗体中任何一项阳性均需排除。乙型肝炎表面抗原阳性需排除;乙型肝炎表面抗原阴性,但乙型肝炎核心抗体阳性同时乙肝病毒DNA 检测结果大于等于各医院参考值上限,需排除; 18. 实验室检查结果异常者: 1) 男性血红蛋白少于90g/L,女性血红蛋白少于85g/L; 2) 白细胞总数少于3.5×109/L; 3) 血小板计数少于80×109/L; 4) AST 或ALT 值高于正常值上限两倍或总胆红素值高于正常值上限; 5) 血清肌酐高于正常值上限; 6) 尿蛋白>1+或尿蛋白检查>1g/L; 7) 便隐血阳性; 8) 其它研究者判断为有临床意义的实验室检查结果,且认为受试者不适合参加本临床试验。 19. 孕期、哺乳期妇女; 20. 签署知情同意书前12 周内参加过任何临床试验者; 21. 研究者、试验中心、申办方和合同研究组织的雇员及相关人员; 22. 因其他情况,研究者认为不适合参加本试验者。 

Exclusion criteria:

1. The spine is completely stiff (fused); 2. Those who have undergone spinal surgery or joint surgery within 24 weeks before randomization; 3. Anyone who is allergic to any test drug ingredient; 4. Previously used TNF antagonists to treat AS, and ineffective or intolerant; 5. Inhibition of other TNF-α including TNF antagonists within 12 weeks prior to randomization Agents or other biological agents such as etanercept, infliximab and adamu monoclonal antibody, etc.; chemical drugs such as thalidomide; 6. Anti-drug antibodies (HAHAs) are positive in laboratory results; 7. Those who have used DMARDs in the first 8 weeks of randomization (except MTX and SSZ); 8. Anyone who has used any immunomodulatory agents within the first 8 weeks of randomization; 9. In the first 4 weeks of randomization, take sulfasalazine (SSZ) > 2g / day, or methotrexate (MTX) > 15mg / week; 10. In the first 4 weeks of randomization, although the dose of sulfasalazine (SSZ) <= 2g / day or methotrexate (MTX) <= 15mg / week, but the dosage changes; 11. In the first 4 weeks of randomization, opioid analgesics (except tramadol) were used; 12. Use NSAIDs or changes in analgesic doses within 4 weeks prior to randomization; 13. Those who use 2 or more NSAIDs in the first 4 weeks of randomization; 14. Those who used Chinese herbal medicine within 8 weeks before randomization; 15. Those who use live (attenuated) vaccines within the first 8 weeks of randomization are known to receive live (attenuated) vaccines during the trial period; 16. Patients who received intra-articular injection, spinal or paravertebral injection of corticosteroids within the first 16 weeks of randomization; 17. Severe concomitant diseases, including: 1) Uncontrolled hypertension (limited to screening period systolic blood pressure > 140mmHg, or screening period diastolic blood pressure > 90mmHg); 2) Myocardial infarction occurred within 12 months prior to the signing of the informed consent form; 3) Unstable angina; 4) Congestive heart failure; 5) Severe lung disease requiring hospitalization or oxygen therapy, chronic bronchitis, obstructive pulmonary disease; 6) Uncontrolled diabetes; 7) Any inflammatory or immune disease other than AS, including but not limited to immunodeficiency syndromes such as Felty syndrome; rheumatoid arthritis; systemic lupus erythematosus; scleroderma or polymyositis; with ankylosing spondylitis Unstable clinical manifestations, such as psoriasis, uveitis, ulcerative colitis, etc.; multiple sclerosis or other central demyelinating diseases; primary dryness syndrome. 8) Combined with chronic liver disease; 9) History of cancer or cancer (except for excised skin basal cell carcinoma or squamous cell carcinoma); 10) Open skin ulcers; 11) Infection within 4 weeks prior to the signing of the informed consent form, and anti-infective treatment is required; 12) Have a history of active tuberculosis or tuberculosis, or chest X-ray examination suggesting previous tuberculosis, or positive gamma interferon release test; 13) Any one of human immunodeficiency virus (HIV) antibodies, Treponema pallidum antibodies, and hepatitis C virus antibodies should be excluded. Hepatitis B surface antigen positive need to be excluded; hepatitis B surface antigen is negative, but hepatitis B core antibody positive and hepatitis B virus DNA detection result is greater than or equal to the hospital reference value upper limit, need to be excluded; 18. Those with abnormal laboratory results: 1) Male hemoglobin is less than 90g / L, female hemoglobin is less than 85g/L; 2) The total number of white blood cells is less than 3.5 x10^9/L; 3) The platelet count is less than 80x10^9/L; 4) The AST or ALT value is more than twice the upper limit of the normal value or the total bilirubin value is above the upper limit of the normal value; 5) Serum creatinine is above the upper limit of normal; 6) Urine protein > 1 + or urine protein test > 1g / L; 7) The occult blood is positive; 8) Other investigators judged the results of clinically meaningful laboratory tests and considered that the subjects were not suitable for this clinical trial. 19. Women during pregnancy and lactation; 20. Those who have participated in any clinical trial within 12 weeks prior to the signing of the informed consent form; 21. Employees and related personnel of researchers, test centres, sponsors and contract research organizations; 22. Due to other circumstances, the investigator considered it inappropriate for the participants. 

研究实施时间:

Study execute time:

From2016-08-31To 2018-02-23 

干预措施:

Interventions:

组别:

试验组

样本量:

402

Group:

Experimental group

Sample size:

干预措施:

重组抗肿瘤坏死因子-α全人源单克隆抗体注射液,40mg/0.8mL,每两周皮下注射一次

干预措施代码:

Intervention:

Recombinant anti-tumor necrosis factor-α whole human monoclonal antibody injection, 40mg/0.8mL, subcutaneous injection every two weeks

Intervention code:

组别:

对照组

样本量:

201

Group:

Control group

Sample size:

干预措施:

修美乐,40mg/0.8mL,每两周皮下注射一次

干预措施代码:

Intervention:

Humira, 40mg/0.8mL, subcutaneous injection every two weeks

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

北京 

市(区县):

 

Country:

China 

Province:

Beijing 

City:

 

单位(医院):

北京大学第一医院 

单位级别:

三甲 

Institution
hospital:

Peking University First Hospital  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

北京 

市(区县):

 

Country:

China 

Province:

Beijing 

City:

 

单位(医院):

北京大学第三医院 

单位级别:

三甲 

Institution
hospital:

Peking University Third Hospital  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

北京 

市(区县):

 

Country:

China 

Province:

Beijing 

City:

 

单位(医院):

中日友好医院 

单位级别:

三甲 

Institution
hospital:

Sino-Japanese Friendship Hospital  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

北京 

市(区县):

 

Country:

China 

Province:

Beijing 

City:

 

单位(医院):

北京医院 

单位级别:

三甲 

Institution
hospital:

Beijing Hospital  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

山西省 

市(区县):

 

Country:

China 

Province:

Shanxi Province 

City:

 

单位(医院):

山西医科大学第二医院 

单位级别:

三甲 

Institution
hospital:

Second Hospital of Shanxi Medical University  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

山西省 

市(区县):

 

Country:

China 

Province:

Shanxi Province 

City:

 

单位(医院):

山西医科大学第一医院 

单位级别:

三甲 

Institution
hospital:

The First Hospital of Shanxi Medical University  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

河北省 

市(区县):

 

Country:

China 

Province:

Hebei Province 

City:

 

单位(医院):

河北医科大学第三医院 

单位级别:

三甲 

Institution
hospital:

The Third Hospital of Hebei Medical University  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

天津市 

市(区县):

 

Country:

China 

Province:

Tianjin 

City:

 

单位(医院):

天津医科大学总医院 

单位级别:

三甲 

Institution
hospital:

Tianjin Medical University General Hospital  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

陕西省 

市(区县):

 

Country:

China 

Province:

Shaanxi Province 

City:

 

单位(医院):

西安交通大学第一附属医院 

单位级别:

三甲 

Institution
hospital:

First Affiliated Hospital of Xi'an Jiaotong University  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

安徽省 

市(区县):

 

Country:

China 

Province:

Anhui Province 

City:

 

单位(医院):

安徽医科大学第一附属医院 

单位级别:

三甲 

Institution
hospital:

The First Affiliated Hospital of Anhui Medical University  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

江苏省 

市(区县):

 

Country:

China 

Province:

Jiangsu Province 

City:

 

单位(医院):

江苏省人民医院 

单位级别:

三甲 

Institution
hospital:

Jiangsu Provincial People's Hospital  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

上海市 

市(区县):

 

Country:

China 

Province:

Shanghai 

City:

 

单位(医院):

复旦大学学附属中山医院 

单位级别:

三甲 

Institution
hospital:

Zhongshan Hospital, Fudan University  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

上海市 

市(区县):

 

Country:

China 

Province:

Shanghai 

City:

 

单位(医院):

复旦大学附属华山医院 

单位级别:

三甲 

Institution
hospital:

Huashan Hospital affiliated to Fudan University  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

上海市 

市(区县):

 

Country:

China 

Province:

Shanghai 

City:

 

单位(医院):

上海长海医院 

单位级别:

三甲 

Institution
hospital:

Shanghai Changhai Hospital  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

上海市 

市(区县):

 

Country:

China 

Province:

Shanghai 

City:

 

单位(医院):

上海市光华中西医结合医院 

单位级别:

三甲 

Institution
hospital:

Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

湖南省 

市(区县):

 

Country:

China 

Province:

Hunan Province 

City:

 

单位(医院):

中南大学湘雅医院 

单位级别:

三甲 

Institution
hospital:

Xiangya Hospital, Central South University  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

湖南省 

市(区县):

 

Country:

China 

Province:

Hunan Province 

City:

 

单位(医院):

中南大学湘雅二医院 

单位级别:

三甲 

Institution
hospital:

The Second Xiangya Hospital of Central South University  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

湖南省 

市(区县):

 

Country:

China 

Province:

Hunan Province 

City:

 

单位(医院):

株洲市中心医院 

单位级别:

三甲 

Institution
hospital:

Zhuzhou Central Hospital  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

浙江省 

市(区县):

 

Country:

China 

Province:

Zhejiang Province 

City:

 

单位(医院):

浙江大学医学院附属第二医院 

单位级别:

三甲 

Institution
hospital:

The Second Affiliated Hospital Zhejiang University School of Medicine  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

四川省 

市(区县):

 

Country:

China 

Province:

Sichuan Province 

City:

 

单位(医院):

四川大学华西医院 

单位级别:

三甲 

Institution
hospital:

West China Hospital,Sichuan University  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

云南省 

市(区县):

 

Country:

China 

Province:

Yunnan Province 

City:

 

单位(医院):

昆明医科大学第一附属医院 

单位级别:

三甲 

Institution
hospital:

First Affiliated Hospital of Kunming Medical University  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

黑龙江省 

市(区县):

 

Country:

China 

Province:

Heilongjiang Province 

City:

 

单位(医院):

哈尔滨医科大学附属第一医院 

单位级别:

三甲 

Institution
hospital:

The First Affiliated Hospital of Harbin Medical University  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

湖北省 

市(区县):

 

Country:

China 

Province:

Hubei Province 

City:

 

单位(医院):

华中科技大学同济医学院附属同济医院 

单位级别:

三甲 

Institution
hospital:

Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

山东省 

市(区县):

 

Country:

China 

Province:

Shandong Province 

City:

 

单位(医院):

山东大学齐鲁医院 

单位级别:

三甲 

Institution
hospital:

Qilu Hospital of Shandong University  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

湖北省 

市(区县):

 

Country:

China 

Province:

Hubei Province 

City:

 

单位(医院):

华中科技大学同济医学院附属协和医院 

单位级别:

三甲 

Institution
hospital:

Union Hospital of Tongji Medical College, Huazhong University of Science and Technology  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

广东省 

市(区县):

 

Country:

China 

Province:

Guangdong Province 

City:

 

单位(医院):

广东省第二人民医院 

单位级别:

三甲 

Institution
hospital:

Guangdong Second People's Hospital  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

北京市 

市(区县):

 

Country:

China 

Province:

Beijing 

City:

 

单位(医院):

中国医学科学院北京协和医院 

单位级别:

三甲 

Institution
hospital:

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences  

Level of the institution:

Tertiary A 

测量指标:

Outcomes:

指标中文名:

24周达到ASAS 20反应的受试者所占百分比

指标类型:

主要指标 

Outcome:

Percentage of subjects who achieved ASAS 20 response at 24 weeks;

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周达到ASAS 20 反应的受试者所占百分比;

指标类型:

次要指标 

Outcome:

Percentage of subjects who achieved ASAS 20 response at 12 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周达到ASAS 40 反应的受试者所占百分比;

指标类型:

次要指标 

Outcome:

Percentage of subjects who achieved ASAS 40 response at 12 weeks and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周达到BASDAI 50 反应的受试者所占百分比;

指标类型:

次要指标 

Outcome:

Percentage of subjects who achieved a BASDAI 50 response at 12 weeks and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周达到ASAS 5/6 改善程度受试者比例;

指标类型:

次要指标 

Outcome:

The proportion of subjects achieving ASAS 5/6 improvement at 12 weeks and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周的晨僵严重程度(BASDAI 问题5 和6 的平均值)。

指标类型:

次要指标 

Outcome:

Morning stiffness at 12 and 24 weeks (average of BASDAI questions 5 and 6).

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周受试者C 反应蛋白值(CRP)和血沉值(ESR)的 改善

指标类型:

次要指标 

Outcome:

Improvements in CRP and ESR at 12 and 24 weeks

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周受试者强直性脊柱炎疾病活动度评分 (ASDAS)的 改善;

指标类型:

次要指标 

Outcome:

Improvements in the ankylosing spondylitis disease activity score (ASDAS) at 12 and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周肿胀关节计数(46 个关节)的改善;

指标类型:

次要指标 

Outcome:

Improvement in swollen joint counts (46 joints) at 12 weeks and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周压痛关节计数(46 个关节)的改善;

指标类型:

次要指标 

Outcome:

Improvement in tender joint count (46 joints) at 12 weeks and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周Bath 强直性脊柱炎疾病活动性指数(BASDAI)评 分的改善;

指标类型:

次要指标 

Outcome:

Improvements in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score at 12 and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周线性Bath 强直性脊柱炎计量指数(BASMIlin)评 分的改善

指标类型:

次要指标 

Outcome:

Improvement of the linear Bath Ankylosing Spondylitis Index (BASMIlin) score at 12 and 24 weeks

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周胸廓扩张度的改善;

指标类型:

次要指标 

Outcome:

Improvement in thoracic dilatation at 12 and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周Maastricht 强直性脊柱炎肌腱端炎积分(MASES) 的改善;

指标类型:

次要指标 

Outcome:

Maastricht ankylosing spondylitis tendonitis score (MASES) improvement at 12 weeks and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周疾病活动性的医生整体评价的改善;

指标类型:

次要指标 

Outcome:

Improvement in overall evaluation of doctors with disease activity at 12 weeks and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周疾病活动性的受试者整体评价的改善;

指标类型:

次要指标 

Outcome:

Improvement in overall evaluation of subjects with disease activity at 12 weeks and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周受试者整体疼痛评价的改善;

指标类型:

次要指标 

Outcome:

Improvement in overall pain assessment of subjects at 12 and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周夜间痛VAS 的改善;

指标类型:

次要指标 

Outcome:

Improvement of painful VAS at night for 12 weeks and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周总背痛VAS 的改善;

指标类型:

次要指标 

Outcome:

Improvement of total back pain VAS at 12 weeks and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周Bath 强直性脊柱炎受试者整体评分(BAS-G)的改 善;

指标类型:

次要指标 

Outcome:

Improvement in overall score (BAS-G) of subjects with Abdominal Spondylitis at 12 weeks and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12 周和24 周Bath 强直性脊柱炎功能指数(BASFI)的改善;

指标类型:

次要指标 

Outcome:

Improvements in the Bath Ankylosing Spondylitis Function Index (BASFI) at 12 and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12周和24周强直性脊柱炎健康评价问卷(HAQ-S)的改善;

指标类型:

次要指标 

Outcome:

Improvement of the 12-week and 24-week ankylosing spondylitis health assessment questionnaire (HAQ-S);

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

12周和24周SF-36V2健康调查问卷(SF-36)的改善;

指标类型:

次要指标 

Outcome:

Improvement of the SF-36V2 Health Questionnaire (SF-36) at 12 weeks and 24 weeks;

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

将评估至少给药1次的全部受试者的安全性,还将评估以下变量: 症状、体格、生命体征、实验室检查、心电图和不良事件。

指标类型:

次要指标 

Outcome:

The safety of all subjects who will be administered at least once will be assessed and the following variables will be assessed: symptoms, physique, vital signs, laboratory tests, electrocardiograms, and adverse events.

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

抗药物抗体(HAHAs),必要时对中和抗体(NAb)进行检测

指标类型:

次要指标 

Outcome:

Antidrug antibody (HAHAs), neutralizing antibody (NAb) is tested when necessary

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

达稳态后给药间隔内血药浓度-时间曲线下面积(AUC)

指标类型:

次要指标 

Outcome:

Area under the plasma concentration-time curve (AUC) within the dosing interval after steady state

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

稳态时最高血药浓度(Cmax、ss)

指标类型:

次要指标 

Outcome:

Maximum blood concentration (Cmax, ss) at steady state

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

稳态时平均血药浓度(Cav,ss )

指标类型:

次要指标 

Outcome:

Average plasma concentration at steady state (Cav, ss)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

稳态时最低血药浓度(Cmin,ss)

指标类型:

次要指标 

Outcome:

Minimum blood concentration at steady state (Cmin, ss)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

消除半衰期(T1/2)

指标类型:

次要指标 

Outcome:

Elimination half-life (T1/2)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

稳态时总清除率(CLss/F)

指标类型:

次要指标 

Outcome:

Total clearance at steady state (CLss/F)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

稳态时表观分布容积(Vss/F)

指标类型:

次要指标 

Outcome:

Apparent distribution volume at steady state (Vss/F)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

最低血药浓度(Cmin)

指标类型:

次要指标 

Outcome:

Minimum blood concentration (Cmin)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

用药后达到最大血药浓度的时间(Tmax)

指标类型:

次要指标 

Outcome:

Time to reach maximum plasma concentration after administration (Tmax)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

炎症活动性指标(C-反应蛋白、血沉)

指标类型:

次要指标 

Outcome:

Inflammatory activity index (C-reactive protein, ESR)

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:

标本中文名:

粪便

组织:

Sample Name:

stool

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:

结束

Completed

年龄范围:

Participant age:

最小 Min age years
最大 Max age 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):

随机方法: 进入试验的受试者经中央随机系统(IWRS)按年龄(<40岁,≥40岁),C-反应蛋白(<28.0mg/L,≥28.0mg/L)和中心进行分层的随机区组设计,随机分配到试验组和对照组(2:1)。

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

Random method: Subjects who entered the trial were randomized to a central randomized system (IWRS) by age (<40 years, >=40 years), C-reactive protein (<28.0 mg/L, >=28.0 mg/L), and the center. The group design was randomly assigned to the test group and the control group (2:1).

盲法:

双盲

Blinding:

Double blind

原始数据公开时间:

The time of sharing IPD:

Within six months after the trial complete

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):

Resman:http://www.medresman.org/register.aspx

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

Resman:http://www.medresman.org/register.aspx

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:

病例记录表和电子采集和管理系统

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

a CRF and an electronic data capture

数据管理委员会:

Data Managemen Committee:

有/Yes

注册人:

Name of Registration:

 2019-04-15
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