The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02172950




Registration number
NCT02172950
Ethics application status
Date submitted
23/06/2014
Date registered
24/06/2014
Date last updated
27/10/2021

Titles & IDs
Public title
An Open-label Safety and Efficacy Study of Recombinant FVIII in Patients With Severe Hemophilia A
Scientific title
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
Secondary ID [1] 0 0
2013-003262-13
Secondary ID [2] 0 0
CSL627_3001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia A 0 0
Severe Hemophilia A 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - rVIII-SingleChain

Experimental: Previously treated patients (PTPs) - The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

Experimental: Previously untreated patients (PUPs) - The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.


Treatment: Other: rVIII-SingleChain
Recombinant single-chain coagulation factor VIII

Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Inhibitor Formation to FVIII in Previously Treated Patients (PTPs) With 100 Exposure Days (EDs) to CSL627
Timepoint [1] 0 0
At the closest visit after 100 EDs (up to 5 years).
Primary outcome [2] 0 0
Number of Previously Untreated Patients (PUPs) With High-titer Inhibitor Formation to FVIII With at Least 50 EDs to CSL627
Timepoint [2] 0 0
At the closest visit after 50 EDs (up to 5 years).
Primary outcome [3] 0 0
Percent Treatment Success for Major Bleeding Episodes in PUPs
Timepoint [3] 0 0
Up to 5 years
Primary outcome [4] 0 0
Annualized Spontaneous Bleeding Rate in PUPs
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [1] 0 0
Percentage of Bleeding Episodes Treated Successfully in PTPs
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
Annualized Bleeding Rate in PTPs and PUPs
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
Mean Number of On-demand Infusions of CSL627
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
Mean On-demand Dose Administered of CSL627
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
Mean Prophylaxis Dose Administered of CSL627
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
Mean Total Amount of CSL627 Administered During Surgery Period in PTPs
Timepoint [7] 0 0
Day of surgery up to 336 hours post-surgery
Secondary outcome [8] 0 0
Total Amount of CSL627 Administered During Surgery Period in PUPs
Timepoint [8] 0 0
Day of surgery up to 336 hours post-surgery
Secondary outcome [9] 0 0
Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery
Timepoint [9] 0 0
From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)
Secondary outcome [10] 0 0
Incidence of Inhibitor Formation to FVIII in PTPs After 10 EDs and After 50 EDs
Timepoint [10] 0 0
Up to 5 years
Secondary outcome [11] 0 0
Percentage of PTPs and PUPs Developing Antibodies Against CSL627
Timepoint [11] 0 0
PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).
Secondary outcome [12] 0 0
Percentage of PTPs and PUPs Developing Antibodies to Chinese Hamster Ovary (CHO) Proteins
Timepoint [12] 0 0
PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).
Secondary outcome [13] 0 0
Number of PUPs With High-titer Inhibitor Formation to FVIII After 10 EDs With CSL627
Timepoint [13] 0 0
At the closest visit after 10 EDs (up to 5 years)
Secondary outcome [14] 0 0
Number of PUPs With Low-titer Inhibitor Formation to FVIII After 10 EDs and After 50 EDs With CSL627
Timepoint [14] 0 0
At the closest visit after 10 and after 50 EDs (up to 5 years)
Secondary outcome [15] 0 0
Incidence of Total Inhibitor Formation to FVIII in PUPs
Timepoint [15] 0 0
Up to 5 years
Secondary outcome [16] 0 0
Percent Treatment Success for Non-major Bleeding Episodes in PUPs
Timepoint [16] 0 0
Up to 5 years
Secondary outcome [17] 0 0
Percentage of PUPs With Clinically Significant Abnormal Vital Signs Values After First Infusion of CSL627
Timepoint [17] 0 0
Up to 6 hours after first infusion
Secondary outcome [18] 0 0
Percentage of PUPs With Treatment-emergent Clinically Significant Abnormal Vital Signs Values
Timepoint [18] 0 0
Up to 5 years

Eligibility
Key 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.
Minimum age
No limit
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Study Site 0360014 - Melbourne
Recruitment hospital [2] 0 0
Study Site 0360028 - Nedlands
Recruitment hospital [3] 0 0
Study Site 0360031 - Perth
Recruitment postcode(s) [1] 0 0
3052 - Melbourne
Recruitment postcode(s) [2] 0 0
WA 6009 - Nedlands
Recruitment postcode(s) [3] 0 0
WA 6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Wisconsin
Country [9] 0 0
Austria
State/province [9] 0 0
Graz
Country [10] 0 0
Austria
State/province [10] 0 0
Linz
Country [11] 0 0
Austria
State/province [11] 0 0
Wien
Country [12] 0 0
Canada
State/province [12] 0 0
Saint John
Country [13] 0 0
Czechia
State/province [13] 0 0
Hradec Kralove
Country [14] 0 0
France
State/province [14] 0 0
Brest
Country [15] 0 0
France
State/province [15] 0 0
Le Kremlin Bicetre
Country [16] 0 0
France
State/province [16] 0 0
Lille Cedex
Country [17] 0 0
France
State/province [17] 0 0
Nantes
Country [18] 0 0
France
State/province [18] 0 0
Paris
Country [19] 0 0
Georgia
State/province [19] 0 0
Tbilisi
Country [20] 0 0
Germany
State/province [20] 0 0
Bonn
Country [21] 0 0
Germany
State/province [21] 0 0
Frankfurt
Country [22] 0 0
Germany
State/province [22] 0 0
Giessen
Country [23] 0 0
Germany
State/province [23] 0 0
Hannover
Country [24] 0 0
Hungary
State/province [24] 0 0
Debrecen
Country [25] 0 0
Ireland
State/province [25] 0 0
Dublin
Country [26] 0 0
Italy
State/province [26] 0 0
Milano
Country [27] 0 0
Japan
State/province [27] 0 0
Hyogo
Country [28] 0 0
Japan
State/province [28] 0 0
Nagoya
Country [29] 0 0
Japan
State/province [29] 0 0
Okayama
Country [30] 0 0
Japan
State/province [30] 0 0
Saitama
Country [31] 0 0
Japan
State/province [31] 0 0
Tokyo
Country [32] 0 0
Lebanon
State/province [32] 0 0
Beirut
Country [33] 0 0
Malaysia
State/province [33] 0 0
Kuala Lumpur
Country [34] 0 0
Netherlands
State/province [34] 0 0
Amsterdam Zuidoost
Country [35] 0 0
Netherlands
State/province [35] 0 0
Nijmegen
Country [36] 0 0
Netherlands
State/province [36] 0 0
Utrecht
Country [37] 0 0
Philippines
State/province [37] 0 0
Cebu City
Country [38] 0 0
Philippines
State/province [38] 0 0
Davao City
Country [39] 0 0
Poland
State/province [39] 0 0
Gdansk
Country [40] 0 0
Poland
State/province [40] 0 0
Krakow
Country [41] 0 0
Poland
State/province [41] 0 0
Rzeszow
Country [42] 0 0
Poland
State/province [42] 0 0
Wroclaw
Country [43] 0 0
Portugal
State/province [43] 0 0
Porto
Country [44] 0 0
Romania
State/province [44] 0 0
Bucharest
Country [45] 0 0
Romania
State/province [45] 0 0
Timisoara
Country [46] 0 0
South Africa
State/province [46] 0 0
Parktown
Country [47] 0 0
Spain
State/province [47] 0 0
A Coruna
Country [48] 0 0
Spain
State/province [48] 0 0
Barcelona
Country [49] 0 0
Spain
State/province [49] 0 0
Madrid
Country [50] 0 0
Spain
State/province [50] 0 0
Valencia
Country [51] 0 0
Switzerland
State/province [51] 0 0
Luzern
Country [52] 0 0
Thailand
State/province [52] 0 0
Bangkok
Country [53] 0 0
Thailand
State/province [53] 0 0
Chiang Mai
Country [54] 0 0
Thailand
State/province [54] 0 0
Khon Kaen
Country [55] 0 0
Thailand
State/province [55] 0 0
Songkhla
Country [56] 0 0
Ukraine
State/province [56] 0 0
Dnipropetrovsk
Country [57] 0 0
Ukraine
State/province [57] 0 0
Lviv
Country [58] 0 0
United Kingdom
State/province [58] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
CSL Behring
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Program Director
Address 0 0
CSL Behring
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.