PMID- 36796484
OWN - NLM
STAT- MEDLINE
DCOM- 20230515
LR  - 20230525
IS  - 1538-7836 (Electronic)
IS  - 1538-7836 (Linking)
VI  - 21
IP  - 6
DP  - 2023 Jun
TI  - Preclinical studies of a factor X activator and a phase 1 trial for hemophilia 
      patients with inhibitors.
PG  - 1453-1465
LID - S1538-7836(23)00148-4 [pii]
LID - 10.1016/j.jtha.2023.01.040 [doi]
AB  - BACKGROUND: Bleeding episodes in hemophiliacs with inhibitors are difficult to 
      control. Staidson protein-0601 (STSP-0601), a specific factor (F)X activator 
      purified from the venom of Daboia russelii siamensis, has been developed. 
      OBJECTIVES: We aimed to investigate the efficacy and safety of STSP-0601 in 
      preclinical and clinical studies. METHODS: In vitro and in vivo preclinical 
      studies were performed. A phase 1, first-in-human, multicenter, and open-label 
      trial was conducted. The clinical study was divided into parts A and B. 
      Hemophiliacs with inhibitors were eligible for this study. Patients received a 
      single intravenous injection of STSP-0601 (0.01 U/kg, 0.04 U/kg, 0.08 U/kg, 0.16 
      U/kg, 0.32 U/kg, or 0.48 U/kg) in part A or a maximum of 6 4-hourly injections 
      (0.16 U/kg) in part B. The primary endpoint for each part was the number of 
      adverse events (AEs) from baseline to 168 hours after administration. This study 
      was registered at clinicaltrials.gov (NCT-04747964 and NCT-05027230). RESULTS: 
      Preclinical studies showed that STSP-0601 could specifically activate FX in a 
      dose-dependent manner. In the clinical study, 16 patients in part A and 7 
      patients in part B were enrolled. Eight (22.2%) AEs in part A and 18 (75.0%) AEs 
      in part B were reported to be related to STSP-0601. Neither severe AEs nor 
      dose-limiting toxicity events were reported. There were no thromboembolic event. 
      The antidrug antibody of STSP-0601 was not detected. CONCLUSION: Preclinical and 
      clinical studies showed that STSP-0601 had a good ability to activate FX and had 
      a good safety profile. STSP-0601 could be used as a hemostatic treatment in 
      hemophiliacs with inhibitors.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Liu, Wei
AU  - Liu W
AD  - State Key Laboratory of Experimental Hematology, National Clinical Research 
      Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of 
      Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood 
      Diseases, Chinese Academy of Medical Sciences Key Laboratory of Gene Therapy for 
      Blood Diseases, Tianjin, China.
FAU - Xue, Feng
AU  - Xue F
AD  - State Key Laboratory of Experimental Hematology, National Clinical Research 
      Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of 
      Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood 
      Diseases, Chinese Academy of Medical Sciences Key Laboratory of Gene Therapy for 
      Blood Diseases, Tianjin, China.
FAU - Fu, Rongfeng
AU  - Fu R
AD  - State Key Laboratory of Experimental Hematology, National Clinical Research 
      Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of 
      Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood 
      Diseases, Chinese Academy of Medical Sciences Key Laboratory of Gene Therapy for 
      Blood Diseases, Tianjin, China.
FAU - Ding, Bingjie
AU  - Ding B
AD  - Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University 
      & Henan Cancer Hospital, Hemostasis and Thrombosis Diagnostic Engineering 
      Research Center of Henan Province, Zhengzhou, China.
FAU - Li, Mengjuan
AU  - Li M
AD  - Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University 
      & Henan Cancer Hospital, Hemostasis and Thrombosis Diagnostic Engineering 
      Research Center of Henan Province, Zhengzhou, China.
FAU - Sun, Ting
AU  - Sun T
AD  - State Key Laboratory of Experimental Hematology, National Clinical Research 
      Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of 
      Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood 
      Diseases, Chinese Academy of Medical Sciences Key Laboratory of Gene Therapy for 
      Blood Diseases, Tianjin, China.
FAU - Chen, Yunfei
AU  - Chen Y
AD  - State Key Laboratory of Experimental Hematology, National Clinical Research 
      Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of 
      Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood 
      Diseases, Chinese Academy of Medical Sciences Key Laboratory of Gene Therapy for 
      Blood Diseases, Tianjin, China.
FAU - Liu, Xiaofan
AU  - Liu X
AD  - State Key Laboratory of Experimental Hematology, National Clinical Research 
      Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of 
      Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood 
      Diseases, Chinese Academy of Medical Sciences Key Laboratory of Gene Therapy for 
      Blood Diseases, Tianjin, China.
FAU - Ju, Mankai
AU  - Ju M
AD  - State Key Laboratory of Experimental Hematology, National Clinical Research 
      Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of 
      Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood 
      Diseases, Chinese Academy of Medical Sciences Key Laboratory of Gene Therapy for 
      Blood Diseases, Tianjin, China.
FAU - Dai, Xinyue
AU  - Dai X
AD  - State Key Laboratory of Experimental Hematology, National Clinical Research 
      Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of 
      Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood 
      Diseases, Chinese Academy of Medical Sciences Key Laboratory of Gene Therapy for 
      Blood Diseases, Tianjin, China.
FAU - Wu, Quanrui
AU  - Wu Q
AD  - Staidson (Beijing) Biopharmaceuticals Co, Ltd, Beijing, China.
FAU - Zhou, Zan
AU  - Zhou Z
AD  - Staidson (Beijing) Biopharmaceuticals Co, Ltd, Beijing, China.
FAU - Yu, Jiaojiao
AU  - Yu J
AD  - Staidson (Beijing) Biopharmaceuticals Co, Ltd, Beijing, China.
FAU - Wang, Xiaomin
AU  - Wang X
AD  - Staidson (Beijing) Biopharmaceuticals Co, Ltd, Beijing, China.
FAU - Zhu, Qing
AU  - Zhu Q
AD  - Staidson (Beijing) Biopharmaceuticals Co, Ltd, Beijing, China.
FAU - Zhou, Hu
AU  - Zhou H
AD  - Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University 
      & Henan Cancer Hospital, Hemostasis and Thrombosis Diagnostic Engineering 
      Research Center of Henan Province, Zhengzhou, China. Electronic address: 
      tigerzhoupumc@163.com.
FAU - Yang, Renchi
AU  - Yang R
AD  - State Key Laboratory of Experimental Hematology, National Clinical Research 
      Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of 
      Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood 
      Diseases, Chinese Academy of Medical Sciences Key Laboratory of Gene Therapy for 
      Blood Diseases, Tianjin, China. Electronic address: rcyang@ihcams.ac.cn.
FAU - Zhang, Lei
AU  - Zhang L
AD  - State Key Laboratory of Experimental Hematology, National Clinical Research 
      Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of 
      Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood 
      Diseases, Chinese Academy of Medical Sciences Key Laboratory of Gene Therapy for 
      Blood Diseases, Tianjin, China. Electronic address: zhanglei1@ihcams.ac.cn.
LA  - eng
SI  - ClinicalTrials.gov/NCT04747964
SI  - ClinicalTrials.gov/NCT05027230
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20230214
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - EC 3.4.22.26 (cancer procoagulant)
RN  - 0 (Neoplasm Proteins)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - 0 (Antibodies)
SB  - IM
CIN - J Thromb Haemost. 2023 Jun;21(6):1429-1431. doi: 10.1016/j.jtha.2023.02.026. 
      PMID: 37179074
MH  - Humans
MH  - *Hemophilia A/diagnosis/drug therapy
MH  - Neoplasm Proteins
MH  - Cysteine Endopeptidases
MH  - Antibodies
OTO - NOTNLM
OT  - FX activator
OT  - clinical trial
OT  - hemophilia
OT  - inhibitors
OT  - preclinical study
COIS- Declaration of competing interest Z.Z., J.Y., X.W., Q.W., and Q.Z. are employees 
      of Staidson (Beijing) Biopharmaceuticals Co, Ltd. The remaining authors report no 
      competing interests to disclose.
EDAT- 2023/02/17 06:00
MHDA- 2023/05/15 06:42
CRDT- 2023/02/16 19:23
PHST- 2022/07/26 00:00 [received]
PHST- 2023/01/10 00:00 [revised]
PHST- 2023/01/30 00:00 [accepted]
PHST- 2023/05/15 06:42 [medline]
PHST- 2023/02/17 06:00 [pubmed]
PHST- 2023/02/16 19:23 [entrez]
AID - S1538-7836(23)00148-4 [pii]
AID - 10.1016/j.jtha.2023.01.040 [doi]
PST - ppublish
SO  - J Thromb Haemost. 2023 Jun;21(6):1453-1465. doi: 10.1016/j.jtha.2023.01.040. Epub 
      2023 Feb 14.