Recombinant Single-chain Factor VIII (rVIII-SingleChain) in Chinese Participants With Hemophilia A Previously Treated With FVIII Products

A Phase 3, Open-label, Multicenter, Pharmacokinetics, Efficacy, and Safety Study of a Recombinant Single-chain Factor VIII (rVIII-SingleChain) in Chinese Previously Treated Patients (PTPs) With Hemophilia A

For bridging the available global clinical data of rVIII-SingleChain, with the Chinese population, the aim of this study in China is to investigate the pharmacokinetics (PK) of rVIII-SingleChain after an initial and repeat dose and to assess efficacy and safety during 2 to 3 times weekly prophylaxis treatment with rVIII-SingleChain in male Chinese PTPs with severe hemophilia A (FVIII activity less than [<] 1%).

Study Overview

• Status: Active, not recruiting
• Conditions: Congenital Hemophilia A
• Intervention / Treatment: Biological: Recombinant single-chain factor VIII (rVIII-SingleChain)

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • The second hospital of Anhui medical university
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100045
      • Beijing Children's Hospital
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400014
      • Children's Hospital of Chongqing Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510623
      • Guangzhou Women And Children's Medical Center
    • Guangzhou, Guangdong, China, 515399
      • Nanfang Hospital of Southern Medical University
  • Guangxi
    • Liuchow, Guangxi, China, 545006
      • Liuzhou people's Hospital
  • Hebei
    • Tangshan, Hebei, China, 63000
      • North China University of Science and Technology Affiliated Hospital
    • Tianjin, Hebei, China, 300020
      • Hospital of Hematology, Chinese Academy of Medical Sciences
  • Henan
    • Zhengzhou, Henan, China, 450053
      • Henan Children's Hospital Zhengzhou Children's Hospital
  • Hunan
    • Changsha, Hunan, China, 410021
      • Hunan Provincial Children's Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Children's Hospital
    • Xuzhou, Jiangsu, China, 221006
      • Xuzhou Children's Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 212028
      • Jiangxi Provincial People's Hospital
  • Qinghai
    • Xining, Qinghai, China, 81000
      • Quinghai Provincial People's Hospital
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
    • Qingdao, Shandong, China, 266071
      • Qingdao Women and Children's Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200020
      • Shanghai Jiaotong University School of Medicine, Ruijin Hospital
  • Yunan
    • Kunming, Yunan, China, 650011
      • The Second Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • The Children's Hospital Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• • Male Chinese participants <= 65 years of age.
• • Participants with severe hemophilia A (FVIII activity < 1%).
• • Participants who have received FVIII products for >= 150 EDs (>= 6 years of age) or >= 50 EDs (< 6 years of age).

Exclusion Criteria:

• • Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or hamster protein.
• • Known congenital or acquired coagulation disorder other than congenital FVIII deficiency.
• • Currently receiving intravenous (IV) immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment.
• • Receiving any cryoprecipitate, whole blood, or plasma within 30 days before administration of rVIII-SingleChain.
• • Use of traditional or herbal Chinese medicine(s) with an impact on hemophilia, including coagulation, within 28 days before Day 1 and / or refusal to abstain from these during the study until the end of the participant's participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rVIII-SingleChain; Participants will receive rVIII-SingleChain as an intravenous (IV) infusion for a minimum of 50 exposure days (EDs).	Biological: Recombinant single-chain factor VIII (rVIII-SingleChain); Lyophilized powder for solution for intravenous injection; Other Names: CSL627

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incremental Recovery (IR) of rVIII-SingleChain		Before, and at 30 minutes after the end of, rVIII-SingleChain administration on Day 1
Maximum Concentration (Cmax) of rVIII-SingleChain		Before, and up to 72 hours (participants ≥ 12 years ) and 48 hours (participants < 12 years) after rVIII-SingleChain administration on Day 1
Area Under the Plasma Concentration Time Curve from Time Zero to the Last Measurable Concentration (AUC0-last) of rVIII-SingleChain		Before, and up to 72 hours (participants ≥ 12 years ) and 48 hours (participants < 12 years) after rVIII-SingleChain administration on Day 1
Area Under the Plasma Concentration Time Curve from Time Zero to Infinity (AUC0-inf) of rVIII-SingleChain		Before, and up to 72 hours (participants ≥ 12 years ) and 48 hours (participants < 12 years) after rVIII-SingleChain administration on Day 1
Half-life (t1/2) of rVIII-SingleChain		Before, and up to 72 hours (participants ≥ 12 years ) and 48 hours (participants < 12 years) after rVIII-SingleChain administration on Day 1
Clearance (Cl) of rVIII-SingleChain		Before, and up to 72 hours (participants ≥ 12 years ) and 48 hours (participants < 12 years) after rVIII-SingleChain administration on Day 1
Annualized Spontaneous Bleeding Rate (AsBR)	AsBR for treated bleeding episodes	Up to 29 weeks after rVIII-SingleChain administration
Number of participants who develop FVIII inhibitors		During routine rVIII-SingleChain prophylaxis dosing, up to 29 weeks after rVIII-SingleChain administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to reach maximum concentration (Tmax) of rVIII-SingleChain		Before, and up to 72 hours (participants ≥ 12 years ) and 48 hours (participants < 12 years) after rVIII-SingleChain administration on Day 1
Last Concentration (Clast) of rVIII-SingleChain	Last observed quantifiable plasma concentration	Before, and up to 72 hours (participants ≥ 12 years ) and 48 hours (participants < 12 years) after rVIII-SingleChain administration on Day 1
IR (participants ≥ 12 years of age) of rVIII-SingleChain (Repeat pharmacokinetic [PK])		Before, and at up to 72 hours after the end of, rVIII-SingleChain infusion at Week 28
Cmax (participants ≥ 12 years of age) of rVIII-SingleChain (Repeat PK)		Before, and at up to 72 hours after the end of, rVIII-SingleChain infusion at Week 28
AUC0-last of rVIII-SingleChain (Repeat PK)		Before, and at up to 72 hours after the end of, rVIII-SingleChain infusion at Week 28
AUC0-inf of rVIII-SingleChain (Repeat PK)		Before, and at up to 72 hours after the end of, rVIII-SingleChain infusion at Week 28
t1/2 of rVIII-SingleChain (participants ≥ 12 years of age) (Repeat PK)		Before, and at up to 72 hours after the end of, rVIII-SingleChain infusion at Week 28
Cl of rVIII-SingleChain (participants ≥ 12 years of age) (Repeat PK)		Before, and at up to 72 hours after the end of, rVIII-SingleChain infusion at Week 28
Annualized Bleeding Rate (ABR)	Total ABR for treated, untreated, and both treated and untreated bleeding episodes (spontaneous, traumatic, and unknown cause)	Up to 29 weeks after rVIII-SingleChain administration
Hemostatic Efficacy for Major and Nonmajor Bleeding Episodes	The investigator will rate the efficacy of the rVIII-SingleChain treatment for major and nonmajor bleeding episodes based on a hemostatic efficacy four point rating scale of "excellent, good, moderate or no efficacy".	Up to 29 weeks after rVIII-SingleChain administration
Consumption of rVIII-SingleChain - number of infusions (doses)		Up to 29 weeks after rVIII-SingleChain administration
Consumption of rVIII-SingleChain - IU/kg per participant per month	rVIII-SingleChain consumption (IU/kg) per participant per month, for the weekly regimen, on-demand treatment, and total treatment.	Up to 29 weeks after rVIII-SingleChain administration
Consumption of rVIII-SingleChain - IU/kg per participant per year	rVIII-SingleChain consumption (IU/kg) per participant per year, for the weekly regimen, on-demand treatment, and total treatment.	Up to 29 weeks after rVIII-SingleChain administration
Number of bleeding episodes requiring rVIII-SingleChain to achieve hemostasis	Number of bleeding episodes requiring 1, <= 2, or > 2 infusions (doses) of rVIII-SingleChain to achieve hemostasis	Up to 29 weeks after rVIII-SingleChain administration
Percentage of bleeding episodes requiring rVIII-SingleChain to achieve hemostasis	Percentage of bleeding episodes requiring 1, <= 2, or > 2 infusions (doses) of rVIII-SingleChain to achieve hemostasis	Up to 29 weeks after rVIII-SingleChain administration
Number of participants who develop noninhibitory antibodies against rVIII-SingleChain		Before, and up to 29 weeks after, rVIII-SingleChain administration
Number of participants who develop antibodies against Chinese hamster ovary host cell protein		Before, and up to 29 weeks after, rVIII-SingleChain administration
Number of participants with Treatment-emergent Adverse Events (TEAEs), including related TEAEs, and serious adverse events (SAEs)		Up to 33 weeks after rVIII-SingleChain administration
Percentage of participants with TEAEs, including related TEAEs, and serious adverse events (SAEs)		Up to 33 weeks after rVIII-SingleChain administration
Number of TEAEs (events)		Up to 33 weeks after rVIII-SingleChain administration

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Study Director, CSL Behring

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2025
• Primary Completion (Estimated): October 26, 2026
• Study Completion (Estimated): October 26, 2026

Study Registration Dates

• First Submitted: December 12, 2024
• First Submitted That Met QC Criteria: December 12, 2024
• First Posted (Actual): December 17, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia A; Coagulants; Factor VIII
• Other Study ID Numbers: CSL627_3003; 2023-001026-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
• IPD Sharing Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (i.e., FDA, EMA) is complete and the primary publication is available.

IPD Sharing Access Criteria

Proposed research should seek to answer a previously unanswered important medical or scientific question.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No