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CME Evaluation

Oral Communication Session

Inherited Bleeding Disorders and Inhibitors

Session: Novel hemophilia treatments, pre-clinical

OC 21.5 - An Open-label,Dose-Escalation,Multicenter Phase I Study to Evaluate the Safety,Immunogenicity,and Pharmacokinetics/pharmacodynamics（PK/PD）of Single Dose SS109 in Hemophilia A/B patients with Inhibitor

Sunday, June 23, 2024
15:45 – 16:00 ICT
Room: Ballroom B1

    Presenting Author(s)

  • Mankai Ju, MD

    Attending Doctor
    State Key Laboratory of Experimental Hematology, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, P.R. China.
    Tianjin, Tianjin, China (People's Republic)

    • Co-Author(s)

  • Feng Xue, MD

    Chief physician
    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, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin 300020, China
    Tianjin, Tianjin, China (People's Republic)

  • ZZ

    Zeping Zhou

    professor
    The Second Affiliated Hospital of Kunming Medical University
    Kunming, Yunnan, China (People's Republic)

  • ZL

    Zhenyu Li

    professor
    The Affiliated Hospital of Xuzhou Medical College, Jiangsu, P.R. China
    Xuzhou, Jiangsu, China (People's Republic)

  • Hu Zhou, MD

    Chief Physician
    Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital
    Zhengzhou, Henan, China (People's Republic)

  • NH

    Ning Huang

    Professor
    The First Affiliated Hospital of Shandong First Medical University, Shandong, P.R. China
    Taian, Shandong, China (People's Republic)

  • WZ

    Wei Zhao

    Professor
    The First Affiliated Hospital of Shandong First Medical University, Shandong, P.R. China
    Taian, Tianjin, China (People's Republic)

  • CZ

    Changcheng Zheng

    Professor
    The First Affiliated Hospital of University of Science and Technology of China,Anhui, P.R. China
    Hefei, Anhui, China (People's Republic)

  • AS

    Aizong Shen

    professor
    Anhui Provincial Hospital, Anhui, P.R. China
    Hefei, Anhui, China (People's Republic)

  • CJ

    Chenghao Jin

    professor
    Jiangxi Provincial People's Hospital, Jiangxi, P.R. China
    Jiangxi, Jiangxi, China (People's Republic)

  • JC

    Jianfang Chen

    Professor
    The Second Hospital of Shanxi Medical University, Shanxi, P.R. China
    Taiyuan, Shanxi, China (People's Republic)

  • YS

    Yanping Song

    Professor
    Xi'an Central Hospital, Shanxi, P.R. China
    Xi'an, Shaanxi, China (People's Republic)

  • Renchi Yang, MD

    Head of Thrombosis and Hemostasis Center
    Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
    Tianjin, Hebei, China (People's Republic)

Background: Bleeding episodes (BEs) in hemophilia patients with inhibitors require the administration of bypassing agents such as activated recombinant human factor VII (rhFVIIa). SS109 is a long-acting rhFVIIa-Fc fusion protein. Nonclinical studies showed that the hemostasis of SS109 is better than that of NovoSeven® in same dose, and half-life is 2.5 times longer than that of NovoSeven® in cynomolgus monkeys.

Aims: To evaluate the safety, immunogenicity, and PK/PD characteristics of single-dose SS109 in hemophilia (FVIII activity ≤1% or FIX activity ≤2%) patients with inhibitors.

Methods: In this first-in-human, open-label, dose-escalation, multi-center study, 27 male patients aged 18-65 years were enrolled. Five doses of SS109 (30, 60, 120, 240, and 360 μg/kg) were examined, and the safety, immunogenicity, and PK/PD were evaluated. This study received approval by each site’s IEC/IRB and written informed consents were obtained from all patients.

Results: Single dose of SS109 at all 5 doses was well-tolerated. Two adverse events occurred in 2 patients (7.4%) were possibly related to SS109. No hypersensitivity or allergic reactions occurred. Table 1 summarizes the baseline-corrected FVII activity PK parameters of SS109. Both the Cmax and the AUC were dose dependent across 5-dose level, with linear dose proportionality being observed within the dose range from 120 to 360μg/kg (Figure 1). The mean half-life ranged from 9.5 hours to14.5 hours, 3 to 7-fold longer than that of NovoSeven®. The aPTT and PT in patients were immediately shortened but returned to the baseline level around 24h and between 48h and 72h, respectively. The maximum reduction (∆Emax) of PT and aPTT after SS109 administration are shown in Table1.

Conclusion(s): This study demonstrated that SS109, a long-acting rhFVIIa-Fc, was well-tolerated and had dose-dependent PK/PD characteristics that support further assessment of its potential hemostasis efficacy in BEs in hemophilia patients with inhibitors.