1. Phase I Clinical Trial on the Tolerability and Pharmacokinetic Characteristics of CHA for Injection in Subjects with Advanced Cancer

From 2014 to 2016, Sichuan Jiuzhang Biotech, the sponsor, took the lead in designing the Phase I clinical trial protocol for CHA for injection according to the safety characteristics of pre-clinical studies of CHA, its pharmacokinetic characteristics, the dosage range of the pharmacodynamic tests, the proposed clinical dosage, and the mode of administration. It also commissioned the Beijing Cancer Hospital to complete the "Phase I Clinical Trial on the Tolerability and Pharmacokinetic Characteristics of CHA for Injection in Subjects with Advanced Cancer" (Trial Registration Number: CTR20130586).

Sponsor's responsible person: Zhang Jie. Main participants: Yang Huarong, Zhang Mengtian, Liao Juan.

Clinical trial institution and PI: Beijing Cancer Hospital, PI: Shen Lin. (Contract Name: Drug Clinical Trial Agreement-Phase I Clinical Study of CHA for Injection, Contract No.: JZ2016008-LC)

CRO service company: Beijing Stamcell Technology Co., Ltd. (Contract Name: Entrusted Contract for Technical Services-Phase I Clinical Study of CHA for Injection, Contract No.: JZ2016002-LC)

SMO service company: Beijing Baisheng Maobo Medical Technology Co., Ltd. (Contract Name: Service Agreement for Providing Clinical Research Coordinator (CRC) Services in Drug Clinical Trials-Phase I Clinical Study of CHA for Injection, Contract No.: JZ2016010-LC)

2. Phase I Clinical Trial on the Safety, Tolerability and Pharmacokinetics of CHA for Injection in the Treatment of Advanced Malignant Glioma

From 2016 to 2017, Sichuan Jiuzhang Biotech, the sponsor, took the lead in designing the Phase I clinical trial protocol for CHA for injection in the treatment of advanced malignant glioma. This was done based on the safety characteristics of the pre-clinical studies of CHA, its pharmacokinetic characteristics, the dosage range of the pharmacodynamic tests, the proposed clinical dosage and the mode of administration, and in combination with the results of the Phase I clinical trial conducted at Beijing Cancer Hospital. It also commissioned Beijing Shijitan Hospital, Capital Medical University to complete the "Phase I Clinical Trial on the Safety, Tolerability and Pharmacokinetics of Chlorogenic Acid for Injection in the Treatment of Advanced Malignant Glioma" (Trial Registration Number: CTR20160113).

Sponsor's responsible person: Zhang Jie. Main participants: Yang Huarong, Zhang Mengtian, Fu Shaohua, Zhou Qian, Liao Juan.

Clinical trial institution and PI: Beijing Shijitan Hospital, Capital Medical University, PI: Li Wenbin. (Contract Name: Phase I Clinical Trial Agreement of CHA for Injection, Contract No.: JZ2016009-LC)

CRO service companies: Beijing Stamcell Technology Co., Ltd. (Contract Name: Entrusted Contract for Technical Services- Phase I Clinical Trial on the Safety, Tolerability and Pharmacokinetics of CHA for Injection in the Treatment of Advanced Malignant Gliomas, Contract No.: JZ2016003-LC)

SMO service companies: Beijing Shunde Kang Medical Technology Co., Ltd. and Beijing Kelinlikang Medical Research Co., Ltd. (Contract Name: Service Agreement for Providing Clinical Research Coordinator (CRC) Services in Drug Clinical Trials- Phase I Clinical Trial on the Safety, Tolerability and Pharmacokinetics of CHA for Injection in the Treatment of Advanced Malignant Gliomas, Contract No.: JZ2016003-1-LC; Contract Name: A Phase I Clinical Trial on the Safety, Tolerability, and Pharmacokinetics of Injectable Chlorogenic Acid in the Treatment of Advanced Malignant Gliomas,  Contract No.: JZ2016004-LC)

Audit service company: Fangen (Tianjin) Pharmaceutical Development Co., Ltd. (Contract Name: Master Agreement for Professional Services - Phase I Clinical Trial Audit Work of Glioma, Contract No.: JZ2017021-JS)

DM+ Statistical analysis company: Department of Health Statistics, Second Military Medical University, Shanghai. (Contract Name: Agreement on the Design, Data Management and Statistical Analysis of the Phase I Clinical Trial for the Study on the Safety, Tolerability and Pharmacokinetics of CHA for Injection in the Treatment of Advanced Malignant Gliomas, Contract No.: JZ2016011-LC)

Pharmacokinetic statistical analysis company: WuXi AppTec Co., Ltd., Shanghai. (Contract Name: Technical Service Contract (Method Development, Method Validation and Sample Analysis (GLP) of LC-MS/MS for Determining the Content of CHA in Human Plasma and Urine), Contract No.: JZ2016012-LC)

Clinical data statistical analysis company: Sipai (Beijing) Medical Technology Co., Ltd. (Contract Name: Master Agreement for the Service of the CHA Clinical Data Statistical Analysis Project, Contract No.: JZ2018016-LC)

3. Randomized, Controlled, Open - label, Multicenter, Phase II / III Clinical Study to Evaluate the Safety and Efficacy of CHA for Injection in the Treatment of Recurrent Grade IV Glioblastoma (GBM)

From 2018 to present, Sichuan Jiuzhang Biotech, the sponsor, took the lead in designing the Phase II/III clinical trial protocol for CHA for injection in the treatment of malignant glioma, based on the results of the Phase I clinical trial of CHA for injection in the treatment of advanced malignant glioma. It also commissioned eleven clinical centers including Beijing Tiantan Hospital, Capital Medical University to conduct the "Randomized, Controlled, Open-label, Multicenter, Phase II /III Clinical Study to Evaluate the Safety and Efficacy of Chlorogenic Acid for Injection in the Treatment of Recurrent Grade IV Glioblastoma (GBM)" (Trial Registration Number: CTR20181644).

Sponsor's responsible person: Zhang Jie. Main participants: Yang Huarong, Liu Mingjie, Zhou Yitao, Liao Juan, Zhu Lina.

Clinical trial institution leading unit and PI:

Beijing Tiantan Hospital, Capital Medical University, PI: Li Wenbin. (Contract Name: Clinical Research Agreement- A Randomized, Controlled, Open-label, Multicenter, Phase II/III Clinical Study to Evaluate the Safety and Efficacy of CHA for Injection in the Treatment of Recurrent Grade IV Glioblastoma Multiforme, Contract No.: JZ2018101-LC)

Other clinical institutions and PIs include:

Chongqing University Cancer Hospital, PI: Cai Run, Mao Deqiang; (Contract Name: Clinical Trial Agreement, Contract No.: JZ2019013-LC)

Shenzhen Second People's Hospital, PI: Li Weiping; (Contract Name: Clinical Trial Agreement, Contract No.: JZ2019053-LC)

Tianjin Huanhu Hospital, PI: Liu Xiaomin; (Contract Name: Clinical Trial Agreement, Contract No.: JZ2019038-LC)

Air Force Medical University Tangdu Hospital, PI: Wang Liang; (Contract Name: Clinical Research Agreement of CHA for Injection, Contract No.: JZ2019060-LC)

Sichuan Provincial People's Hospital, PI: Ao Rui; (Contract Name: Drug Clinical Trial Agreement, Contract No.: JZ2019056-LC)

General Hospital of Ningxia Medical University, PI: Xia Hechun; (Contract Name: Clinical Trial Agreement, Contract No.: JZ2019037-LC)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, PI: Yang Kunyu; (Contract Name: Clinical Trial Agreement, Contract No.: JZ2019026-LC)

Harbin Medical University Cancer Hospital, PI: Su Jun; (Contract Name: Clinical Trial Agreement, Contract No.: JZ2019020-LC)

Jiangsu Provincial People's Hospital, PI: You Yongping; (Contract Name: Clinical Trial Agreement, Contract No.: JZ2019041-LC)

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, PI: Ma Wenbin. (Contract Name: Clinical Trial Agreement-Master Agreement, Contract No.: JZ2020010-LC)

SMO service company: Pures (Shanghai) Pharmaceutical Technology Development Co., Ltd. (Contract Name: Clinical Trial Entrustment Contract, Contract No.:JZ2018098-LC/)

Protocol writing company: Fangen (Beijing) Pharmaceutical Technology Development Co., Ltd. (Contract Name: Master Agreement for Professional Services, Contract No.: JZ2017060-LC)

Audit company: Beijing Jingwei Chuanqi Pharmaceutical Technology Co., Ltd. (Contract Name: Audit Technical Service Contract and Supplementary Contract, Contract No.: JZ2019046-LC)

Subject recruitment service companies: Beijing Spring Pharmaceutical Technology Development Co., Ltd. and Beijing Yifan Fengshun Pharmaceutical Technology Co., Ltd. (Contract Name: Framework Agreement on Clinical Research Cooperation, Contract No.: JZ2021031-LC；Contract Name: Clinical Trial Subject Recruitment Service Agreement, Contract No.: JZ2023035-LC)

Statistical analysis service company: Shengfang (Shanghai) Pharmaceutical R & D Co., Ltd. (Contract Name: Special Service Agreement for the Interim Analysis of Phase II Clinical Trial of Glioma, Contract No.: JZ2021061-LC)

Data management service company: Jiaxing TaiMei Medical Technology Co., Ltd. (Contract Name: Service Agreement and Supplementary Agreement for EDC (Electronic Data Capture), DM (Data Management) and Statistical Analysis of the Randomized, Controlled, Open-label, Multicenter, Phase II/III Clinical Trial of CHA for Injection in the Treatment of Grade IV Glioblastoma Multiforme, Contract No.: JZ2018033-LC)