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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/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
Other interventions - rVIII-SingleChain

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.


Other interventions: rVIII-SingleChain


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

Outcomes
Primary outcome [1] 0 0
Treatment Success - Rate of treatment success where treatment success of a bleeding episode is defined as a rating of "excellent" or "good" based on the investigator's overall clinical assessment of hemostatic efficacy (using a 4-point scale of excellent, good, moderate or poor/no response) on the on-demand and prophylaxis regimens combined. The rate of success was based on the number of treated bleeding events; there were 347 treated bleeding events in the Efficacy Population.
Timepoint [1] 0 0
Up to 1 year
Secondary outcome [1] 0 0
Annualized Bleeding Rate - The annualized bleeding rate was defined as the number of bleeding episodes requiring treatment divided by the efficacy evaluation period in days, x 365.25, and is presented separately for the on-demand regimen and the prophylaxis regimens.
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 - Incremental recovery expressed as (IU/dL)/(IU/kg) corrected for subject's predose plasma FVIII activity measured using the chromogenic substrate assay.
Timepoint [8] 0 0
At 1 hour after the start of infusion
Secondary outcome [9] 0 0
Half-life (t1/2) of rVIII-SingleChain - Half-life (t1/2) of rVIII-SingleChain, baseline uncorrected; plasma FVIII activity measured using the chromogenic substrate assay.
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) - AUC to the last sample with quantifiable drug concentration (AUC0-t), baseline uncorrected; plasma FVIII activity measured using the chromogenic substrate assay.
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 - Clearance (Cl) of rVIII-SingleChain, baseline uncorrected; plasma FVIII activity measured using the chromogenic substrate assay.
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 - The number of subjects who develop inhibitors to rVIII-SingleChain, defined as a rVIII-SingleChain antibody titer of at least 0.6 Bethesda Units (BU) per mL after receiving study drug.
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
Gender
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
N/A
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
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)
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/show/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
Other publications