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

• Register: EUCTR
• Last refreshed on: 17 March 2021
• Main ID: EUCTR2013-003262-13-AT
• Date of registration: 15/07/2014
• Prospective Registration: Yes
• Primary sponsor: CSL Behring GmbH
• Public title: An Open-label Safety and Efficacy Study of Recombinant FVIII in Patients With Severe Hemophilia A
• Scientific title: A Phase 3 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
• Date of first enrolment: 03/09/2014
• Target sample size: 246
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003262-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

• Name: Clin.Trial Registration Coordinator
• Affiliation: CSL Behring GmbH

• Name: Clin.Trial Registration Coordinator
• Affiliation: CSL Behring GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
PTPs:
• Males of any age who have been diagnosed with severe congenital
hemophilia A (FVIII activity levels < 1%) and who participated in a
previous CSL-sponsored clinical study with rVIII-SingleChain.
• Males 0 to <65 years age who have been diagnosed with severe
congenital hemophilia A (FVIII activity levels < 1%), who have at least
50 EDs to any FVIII product, and who are not currently enrolled in a
CSL-sponsored clinical study with rVIII-SingleChain.
PUPs:
• Males 0 to <18 years of who have been diagnosed with severe
congenital hemophilia A (FVIII activity levels < 1%).
• No prior exposure to any Factor VIII product (with the exception of
short-term use of blood products).
ITI substudy:
• PUPs who have developed a confirmed inhibitor to rVIII-SingleChain
in the main study.
Are the trial subjects under 18? yes
Number of subjects for this age range: 114
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 132
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

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

Intervention(s)

Trade Name: Afstyla
Product Name: rVIII-SingleChain
Product Code: CSL627
Pharmaceutical Form: Powder and solvent for solution for injection/infusion
INN or Proposed INN: Lonoctocog alfa
CAS Number: 1388129-63-2
Current Sponsor code: CSL627
Other descriptive name: rVIII-SingleChain
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 250-

Trade Name: Afstyla
Product Name: rVIII-SingleChain
Product Code: CSL627
Pharmaceutical Form: Powder and solvent for solution for injection/infusion
INN or Proposed INN: Lonoctocog alfa
CAS Number: 1388129-63-2
Current Sponsor code: CSL627
Other descriptive name: rVIII-SingleChain
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 500-

Trade Name: Afstyla
Product Name: rVIII-SingleChain
Product Code: CSL627
Pharmaceutical Form: Powder and solvent for solution for injection/infusion
INN or Proposed INN: Lonoctocog alfa
CAS Number: 1388129-63-2
Current Sponsor code: CSL627
Other descriptive name: rVIII-SingleChain
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 1000-

Trade Name: Afstyla
Product Name: rVIII-SingleChain
Product Code: CSL627
Pharmaceutical Form: Powder and solvent for solution for injection/infusion
INN or Proposed INN: Lonoctocog alfa
CAS Number: 1388129-63-2
Current Sponsor code: CSL627
Other descriptive name: rVIII-SingleChain
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 2000-

Trade Name: Afstyla
Product Name: rVIII-SingleChain
Product Code: CSL627
Pharmaceutical Form: Powder and solvent for solution for injection/infusion
INN or Proposed INN: Lonoctocog alfa
CAS Number: 1388129-63-2
Current Sponsor code: CSL627
Other descriptive name: rVIII-Sin

Primary Outcome(s)

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

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:
To:
• characterize safety profile of rVIII-SingleChain regarding:
- inhibitor development after 10 EDs and after 50 EDs
- antibodies against rVIII-SC and antibodies to CHO proteins
• collect + evaluate efficacy information on the prophylaxis and
treatment of bleeding episodes
• assess the hemostatic efficacy of rVIII-SC for PTPs who undergo
surgery
PUPs:
• further characterize the safety profile of rVIII-SC re. inhibitor
development
• characterize the safety profile of rVIII-SC re. antibodies against rVIIISC
+ antibodies to CHO proteins
• collect + evaluate number of injections required for the treatment of
bleeding episodes
• characterize consumption of rVIII-SC in prophylaxis, on-demand
treatment, and surgery
• assess the hemostatic efficacy of rVIII-SC for PUPs who undergo
surgery, using the 4-point efficacy evaluation of surgical treatment scale
• assess occurrence of clinically significant abnormalities in vital signs
after rVIII-SingleChain administration

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

Secondary Outcome(s)

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 10 and 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

Secondary ID(s)

2013-003262-13-IT

CSL627_3001

Source(s) of Monetary Support

CSL Behring GmbH

Ethics review

Status: Approved
Approval date: 03/09/2014
Contact: