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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02093897




Registration number
NCT02093897
Ethics application status
Date submitted
19/03/2014
Date registered
21/03/2014
Date last updated
27/01/2017

Titles & IDs
Public title
Pharmacokinetic, Efficacy, and Safety Study of Recombinant Factor VIII Single Chain (rVIII-SingleChain) in Children With Severe Hemophilia A
Scientific title
A Phase III Open-label Pharmacokinetic, Efficacy and Safety Study of rVIII-SingleChain in a Pediatric Population With Severe Hemophilia A
Secondary ID [1] 0 0
2012-001336-65
Secondary ID [2] 0 0
CSL627_3002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Congenital 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
Experimental: rVIII-SingleChain - Subjects will be assigned to either an on-demand or prophylaxis regimen and will receive rVIII-SingleChain as an intravenous (IV) infusion. Subjects assigned to a prophylaxis regimen will be treated with 15 to 50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based on available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose for on-demand treatment of a bleeding episode is based on the recommendations of the World Federation of Hemophilia (WFH), with a minimum dose of 15 IU/kg. All subjects were to be treated for a minimum of 50 EDs. For the PK evaluation, the subjects will receive a single IV dose of 50 IU/kg of rVIII-SingleChain on Day 1 at the start of the PK evaluation period.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Treatment Success
Timepoint [1] 0 0
Up to 1 year
Secondary outcome [1] 0 0
Annualized Bleeding Rate
Timepoint [1] 0 0
Up to 1 year
Secondary outcome [2] 0 0
Percentage of Bleeding Episodes Requiring 1, 2, 3, or More Than 3 Infusions of rVIII-SingleChain to Achieve Hemostasis.
Timepoint [2] 0 0
Up to 1 year
Secondary outcome [3] 0 0
Consumption of rVIII-SingleChain - IU/kg Per Subject Per Month
Timepoint [3] 0 0
Up to 1 year
Secondary outcome [4] 0 0
Consumption of rVIII-SingleChain - IU/kg Per Subject Per Year
Timepoint [4] 0 0
Up to 1 year
Secondary outcome [5] 0 0
Consumption of rVIII-SingleChain - IU/kg Per Bleeding Event
Timepoint [5] 0 0
Up to 1 year
Secondary outcome [6] 0 0
Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Month
Timepoint [6] 0 0
Up to 1 year
Secondary outcome [7] 0 0
Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Year
Timepoint [7] 0 0
Up to 1 year
Secondary outcome [8] 0 0
Incremental Recovery
Timepoint [8] 0 0
At 1 hour after the start of infusion
Secondary outcome [9] 0 0
Half-life (t1/2) of rVIII-SingleChain
Timepoint [9] 0 0
Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
Secondary outcome [10] 0 0
Area Under the Concentration Curve (AUC)
Timepoint [10] 0 0
Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
Secondary outcome [11] 0 0
Clearance (Cl) of rVIII-SingleChain
Timepoint [11] 0 0
Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
Secondary outcome [12] 0 0
Number of Subjects With Inhibitor Formation to rVIII-SingleChain
Timepoint [12] 0 0
At screening, then after dosing at approximately monthly intervals for 6 months, then every 3 months until reaching 50 EDs, and at the end of study visit (up to approximately 12 months).

Eligibility
Key inclusion criteria
* Diagnosis of severe hemophilia A defined as < 1% Factor VIII (FVIII) concentration (FVIII:C) documented in medical records,
* Males < 12 years of age,
* Subjects who have received > 50 EDs with a FVIII product,
* Prior PK data (at least incremental recovery and half-life) from previous FVIII exposure for subjects participating in the PK part
* Investigator believes that the subject is willing and able to adhere to all protocol requirements. Investigator believes that the subject's parent(s) or legally acceptable representative(s) is / are willing and able to adhere to all protocol requirements.
Minimum age
No limit
Maximum age
11 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Any history of or current FVIII inhibitors
* Use of an Investigational Medical Product (IMP) within 30 days prior to the first rVIII-SingleChain administration,
* Administration of any cryoprecipitate, whole blood or plasma within 30 days prior to administration of rVIII-SingleChain,
* Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or hamster protein,
* Subject currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment,
* Subject with serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) values >5 times (x) the upper limit of normal (ULN) at Screening,
* Subjects with serum creatinine values >2 x ULN at Screening,
* Evidence of thrombosis, including deep vein thrombosis, stroke, pulmonary embolism, myocardial infarction and arterial embolus within 3 months before Day 1,
* Experienced life-threatening bleeding episode or had major surgery or an orthopedic surgical procedure during the 3 months before rVIII-SingleChain administration.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Single group
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
1/03/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2015
Sample size
Target
Accrual to date
Final
84
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Study Site - Melbourne
Recruitment postcode(s) [1] 0 0
3052 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
Austria
State/province [3] 0 0
Linz
Country [4] 0 0
Austria
State/province [4] 0 0
Vienna
Country [5] 0 0
France
State/province [5] 0 0
Brest
Country [6] 0 0
France
State/province [6] 0 0
Le Kremlin Bicetre
Country [7] 0 0
France
State/province [7] 0 0
Lille Cedex
Country [8] 0 0
France
State/province [8] 0 0
Nantes
Country [9] 0 0
France
State/province [9] 0 0
Paris
Country [10] 0 0
Georgia
State/province [10] 0 0
Tbilisi
Country [11] 0 0
Germany
State/province [11] 0 0
Bonn
Country [12] 0 0
Germany
State/province [12] 0 0
Bremen
Country [13] 0 0
Germany
State/province [13] 0 0
Frankfurt/Main
Country [14] 0 0
Germany
State/province [14] 0 0
Hannover
Country [15] 0 0
Italy
State/province [15] 0 0
Milano
Country [16] 0 0
Lebanon
State/province [16] 0 0
Beirut
Country [17] 0 0
Malaysia
State/province [17] 0 0
Kuala Lumpur
Country [18] 0 0
Netherlands
State/province [18] 0 0
Amsterdam
Country [19] 0 0
Netherlands
State/province [19] 0 0
Njmegen
Country [20] 0 0
Netherlands
State/province [20] 0 0
Utrecht
Country [21] 0 0
Philippines
State/province [21] 0 0
Cebu City
Country [22] 0 0
Philippines
State/province [22] 0 0
Davao City
Country [23] 0 0
Poland
State/province [23] 0 0
Rzeszow
Country [24] 0 0
Portugal
State/province [24] 0 0
Oporto
Country [25] 0 0
Romania
State/province [25] 0 0
Timisoara
Country [26] 0 0
Spain
State/province [26] 0 0
Madrid
Country [27] 0 0
Switzerland
State/province [27] 0 0
Lucerne
Country [28] 0 0
Thailand
State/province [28] 0 0
Bangkok
Country [29] 0 0
Thailand
State/province [29] 0 0
Chiang Mai
Country [30] 0 0
Thailand
State/province [30] 0 0
Khon Kaen
Country [31] 0 0
Thailand
State/province [31] 0 0
Songkla
Country [32] 0 0
Turkey
State/province [32] 0 0
Adana
Country [33] 0 0
Turkey
State/province [33] 0 0
Istanbul
Country [34] 0 0
Turkey
State/province [34] 0 0
Izmir
Country [35] 0 0
Ukraine
State/province [35] 0 0
Lviv

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

Ethics approval
Ethics application status

Summary
Brief summary
This is an international, multicenter, open-label study to assess the efficacy, safety, and pharmacokinetic (PK) profile of rVIII-SingleChain in pediatric patients with severe hemophilia A. A minimum of 25 previously treated subjects = 6 to \< 12 years of age and at least 25 subjects \< 6 years of age who have undergone \> 50 exposure days (EDs) with a previous Factor VIII (FVIII) product are planned to be enrolled. Subjects will be assigned to either an on-demand or prophylaxis treatment regimen and will receive rVIII-SingleChain at a dose to be determined by the investigator. Hemostatic efficacy will be assessed by the subject/caregiver and the investigator who will assess overall efficacy by a 4-point scale.
Trial website
https://clinicaltrials.gov/study/NCT02093897
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02093897