Pharmacokinetic, efficacy and safety evaluation of B-domain-deleted recombinant FVIII (SCT800) for prophylactic treatment in adolescent and adult patients with severe haemophilia A.

Abstract

INTRODUCTION:

SCT800 is a recombinant human B-domain-deleted coagulation factor VIII (BDDrFVIII) developed in China.

AIM:

To evaluate the repeat pharmacokinetics (PKs), efficacy, and safety of SCT800 in previously treated Chinese adolescent and adult patients with severe haemophilia A.

METHODS:

A phase III, multicentre, prospective, open-label, single-arm trial was conducted at 12 medical centres. Subjects received treatment for 24 weeks. PKs were assessed at the initial and repeated dosing 24 weeks later. The primary endpoint was annualized bleeding rate (ABR). Breakthrough bleeding episodes and inhibitor development were assessed.

RESULTS:

A total of 71 of 73 patients completed the study, and 18 were enrolled for the repeat PK investigation. Total exposure was 5643 exposure days. Overall, SCT800 showed comparable repeat PK profiles. The total ABR was 2.82 (95% confidence interval 2.01-3.96). During prophylaxis, 43.8% of patients had no bleeding episodes. The majority (89.4%) of bleeding episodes were controlled with 1-2 injections of SCT800, the success rate (defined as 'excellent' or 'good' haemostatic response) for the treatment of bleeding episodes was 92.6%. The incidence of treatment-related adverse events was 53.4%. Drug-related AE incidence was 4.1%. The observed AEs were similar to those of other coagulation factor VIII, but lower in frequency. No subject developed an inhibitor, and no other safety concerns were identified.

CONCLUSIONS:

SCT800 has robust PK characteristics, and is safe and efficacious for the prophylaxis and treatment of bleeding episodes in previously treated adolescent and adult patients with severe haemophilia A.

• Authors: Feng Xue, Xielan Zhao, Jing Sun, Xiaojing Zeng, Fenge Yang, Ming Xu, Ziqiang Yu, Weiying Gu, Ying Feng, Wenqian Li, Changcheng Zheng, Hui Bi, Liangzhi Xie, Wenlin Gai, Renchi Yang
• Journal: Haemophilia : the official journal of the World Federation of Hemophilia (Haemophilia) Vol. 27 Issue 5 Pg. 814-822 (Sep 2021) ISSN: 1365-2516 [Electronic] England
• PMID: 34089210 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study)
• Copyright: © 2021 John Wiley & Sons Ltd.

Chemical References

• Factor VIII

Topics

• Adolescent
• Adult
• Blood Coagulation
• Factor VIII (therapeutic use)
• Hemophilia A (drug therapy)
• Hemorrhage (prevention & control)
• Hemostasis
• Humans
• Prospective Studies
• Treatment Outcome