An Open-label Safety and Efficacy Study of Recombinant FVIII in Patients With Severe Hemophilia A

A Phase III Open Label, Multicenter, Extension Study to Assess the Safety and Efficacy of Recombinant Coagulation Factor VIII (rVIII-SingleChain, CSL627) in Subjects with Severe Hemophilia A

Status

Not yet recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2013-003262-13-GB

Enrollment

250

Registered

2014-05-06

Start date

2014-09-01

Completion date

Unknown

Last updated

2018-04-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hemophilia A Severe hemophilia A MedDRA version: 20.0 Level: LLT Classification code 10060613 Term: Hemophilia A (Factor VIII) System Organ Class: 100000004850

Interventions

Trade Name: Afstyla Product Name: rVIII-SingleChain Product Code: CSL627 Pharmaceutical Form: Powder and solvent for solution for injection INN or Proposed INN: Lonoctocog alfa CAS Number: 1388129-63-

Eligibility

Sex/Gender

Male

Inclusion criteria

Inclusion criteria: PTPs: • Males of any age who have been diagnosed with severe congenital hemophilia A (FVIII activity levels =65 years) yes F.1.3.1 Number of subjects for this age range 1

Exclusion criteria

Exclusion criteria: • Known or suspected hypersensitivity to rVIII-SingleChain or to any excipients of rVIII-SingleChain or Chinese hamster ovary (CHO) proteins. • Currently receiving a therapy not permitted during the study. • Serum creatinine > 2 x upper limit of normal, alanine aminotransferase or aspartate aminotransferase > 5 x upper limit of normal at Screening (if specified) • Any first-order family (eg, siblings) history of FVIII inhibitors • For PTPs not rolling over directly from a CSL-sponsored clinical study with rVIII-SingleChain: any history of or current FVIII inhibitors

Design outcomes

Primary

Measure	Time frame
Main Objective: Previously treated Patients (PTPs): • To characterize the long-term safety profile of rVIII-SingleChain with respect to inhibitor development in PTPs Previously Untreated Patients (PUPs): • To characterize the safety with respect to inhibitor development in PUPs • To evaluate the efficacy of on-demand and prophylaxis treatment of rVIII-SingleChain in PUPs;Secondary Objective: PTPs: • Characterize safety profile of rVIII-SingleChain regarding: - Inhibitor development after 10 and 50 EDs - Antibodies against rVIII-SingleChain and antibodies to CHO proteins • Evaluate efficacy information on prophylaxis and treatment of bleeds • Assess the hemostatic efficacy of rVIII-SingleChain for PTPs who undergo surgery PUPs: • Further characterize safety profile of rVIII-SingleChain regarding inhibitor development • Characterize safety profile of rVIII-SingleChain regarding antibodies against rVIII-SingleChain and antibodies to CHO proteins • Evaluate number of injections required to treat bleeds • Characterize consumption of rVIII-SingleChain in prophylaxis, ondemand treatment, and surgery • Assess hemostatic efficacy of rVIII-SingleChain in surgery • Assess occurrence of clinically significant vital sign abnormalities after rVIII-SingleChain;Primary end point(s): 1. Incidence of inhibitor formation to FVIII in PTPs with 100 EDs to rVIII-SingleChain 2. Incidence of high-titer inhibitor formation to FVIII in at least 50 PUPs with at least 50 EDs of rVIII-SingleChain 3. Treatment success for major bleeding episodes in PUPs 4. Annualized spontaneous bleeding rate in PUPs;Timepoint(s) of evaluation of this end point: 1. At the closest visit after 100 EDs (up to 5 years) 2. At the closest visit after 50 EDs (up to 5 years) 3. Up to 5 years 4. Up to 5 years	—

Measure

Time frame

Main Objective: Previously treated Patients (PTPs): • To characterize the long-term safety profile of rVIII-SingleChain with respect to inhibitor development in PTPs Previously Untreated Patients (PUPs): • To characterize the safety with respect to inhibitor development in PUPs • To evaluate the efficacy of on-demand and prophylaxis treatment of rVIII-SingleChain in PUPs;Secondary Objective: PTPs: • Characterize safety profile of rVIII-SingleChain regarding: - Inhibitor development after 10 and 50 EDs - Antibodies against rVIII-SingleChain and antibodies to CHO proteins • Evaluate efficacy information on prophylaxis and treatment of bleeds • Assess the hemostatic efficacy of rVIII-SingleChain for PTPs who undergo surgery PUPs: • Further characterize safety profile of rVIII-SingleChain regarding inhibitor development • Characterize safety profile of rVIII-SingleChain regarding antibodies against rVIII-SingleChain and antibodies to CHO proteins • Evaluate number of injections required to treat bleeds • Characterize consumption of rVIII-SingleChain in prophylaxis, ondemand treatment, and surgery • Assess hemostatic efficacy of rVIII-SingleChain in surgery • Assess occurrence of clinically significant vital sign abnormalities after rVIII-SingleChain;Primary end point(s): 1. Incidence of inhibitor formation to FVIII in PTPs with 100 EDs to rVIII-SingleChain 2. Incidence of high-titer inhibitor formation to FVIII in at least 50 PUPs with at least 50 EDs of rVIII-SingleChain 3. Treatment success for major bleeding episodes in PUPs 4. Annualized spontaneous bleeding rate in PUPs;Timepoint(s) of evaluation of this end point: 1. At the closest visit after 100 EDs (up to 5 years) 2. At the closest visit after 50 EDs (up to 5 years) 3. Up to 5 years 4. Up to 5 years

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Secondary

Measure	Time frame
Secondary end point(s): 1. Treatment success in PTPs 2. Annualized bleeding rate in PTPs and PUPs 3. Percentage of bleeding episodes requiring 1, 2, 3, or > 3 injections of rVIII-SingleChain to achieve hemostasis in PTPs and PUPs 4. Consumption of rVIII-SingleChain in PTPs and PUPs - injections 5. Consumption of rVIII-SingleChain in PTPs and PUPs - IU/kg 6. Hemostatic efficacy of rVIII-SingleChain for PTPs and PUPs who undergo surgery 7. Incidence of inhibitor formation to FVIII after 10 EDs and after 50 EDs in PTPs 8. Percentage of PTPs and PUPs developing antibodies against rVIIISingleChain 9. Percentage of PTPs and PUPs developing antibodies to Chinese hamster ovary (CHO) proteins 10. Incidence of high-titer inhibitor formation to FVIII in PUPs after 10 EDs with rVIII-SingleChain 11. Incidence of low-titer inhibitor formation to FVIII in PUPs 12. Incidence of total inhibitor formation to FVIII in PUPs 13. Treatment success for non-major bleeding episodes in PUPs 14. Percentage of PUPs with clinically significant abnormal vital signs values after first rVIII-SingleChain injection 15. Percentage of PUPs with treatment-emergent clinically significant abnormal vital signs values;Timepoint(s) of evaluation of this end point: 1, 2, 3, 4, 5: Up to 5 years 6. From the start of surgery through the post-operative recovery (generally up to 14 days after surgery) 7. After 10 EDs and after 50 EDs 8. PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years). 9. PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years) 10. At the closest visit after 10 EDs 11. At the closest visit after 10 and after 50 EDs (up to 5 years) 12. At the closest visit after 50 EDs (up to 5 years). 13. Up to 5 years 14. At 1, 2, 3, and 6 hours after first rVIII-SingleChain injection 15. Up to 5 years	—

Measure

Time frame

Secondary end point(s): 1. Treatment success in PTPs 2. Annualized bleeding rate in PTPs and PUPs 3. Percentage of bleeding episodes requiring 1, 2, 3, or > 3 injections of rVIII-SingleChain to achieve hemostasis in PTPs and PUPs 4. Consumption of rVIII-SingleChain in PTPs and PUPs - injections 5. Consumption of rVIII-SingleChain in PTPs and PUPs - IU/kg 6. Hemostatic efficacy of rVIII-SingleChain for PTPs and PUPs who undergo surgery 7. Incidence of inhibitor formation to FVIII after 10 EDs and after 50 EDs in PTPs 8. Percentage of PTPs and PUPs developing antibodies against rVIIISingleChain 9. Percentage of PTPs and PUPs developing antibodies to Chinese hamster ovary (CHO) proteins 10. Incidence of high-titer inhibitor formation to FVIII in PUPs after 10 EDs with rVIII-SingleChain 11. Incidence of low-titer inhibitor formation to FVIII in PUPs 12. Incidence of total inhibitor formation to FVIII in PUPs 13. Treatment success for non-major bleeding episodes in PUPs 14. Percentage of PUPs with clinically significant abnormal vital signs values after first rVIII-SingleChain injection 15. Percentage of PUPs with treatment-emergent clinically significant abnormal vital signs values;Timepoint(s) of evaluation of this end point: 1, 2, 3, 4, 5: Up to 5 years 6. From the start of surgery through the post-operative recovery (generally up to 14 days after surgery) 7. After 10 EDs and after 50 EDs 8. PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years). 9. PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years) 10. At the closest visit after 10 EDs 11. At the closest visit after 10 and after 50 EDs (up to 5 years) 12. At the closest visit after 50 EDs (up to 5 years). 13. Up to 5 years 14. At 1, 2, 3, and 6 hours after first rVIII-SingleChain injection 15. Up to 5 years

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Countries

Australia, Austria, Canada, Czech Republic, European Union, Georgia, Germany, Hungary, Ireland, Italy, Japan, Lebanon, Malaysia, Netherlands, Philippines, Poland, Portugal, South Africa, Spain, Switzerland, Thailand, Ukraine, United Kingdom, United States

Contacts

Public ContactClin.Trial Registration Coordinator

CSL Behring GmbH

clinicaltrials@cslbehring.com

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026