Clinical trial NCT02093897: Pharmacokinetic, Efficacy, and Safety Study of Recombinant Factor VIII Single Chain (rVIII-SingleChain) in Children With Severe Hemophilia A
Official title: A Phase III Open-label Pharmacokinetic, Efficacy and Safety Study of rVIII-SingleChain in a Pediatric Population With Severe Hemophilia A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Congenital Hemophilia A
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2014-03-21
Enrollment: 84
Sex: MALE
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

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.

Primary outcomes:
measure: Treatment Success
timeFrame: Up to 1 year
Secondary outcomes:
measure: Annualized Bleeding Rate
timeFrame: Up to 1 year
measure: Percentage of Bleeding Episodes Requiring 1, 2, 3, or More Than 3 Infusions of rVIII-SingleChain to Achieve Hemostasis.
timeFrame: Up to 1 year
measure: Consumption of rVIII-SingleChain - IU/kg Per Subject Per Month
timeFrame: Up to 1 year
measure: Consumption of rVIII-SingleChain - IU/kg Per Subject Per Year
timeFrame: Up to 1 year
measure: Consumption of rVIII-SingleChain - IU/kg Per Bleeding Event
timeFrame: Up to 1 year
measure: Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Month
timeFrame: Up to 1 year
measure: Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Year
timeFrame: Up to 1 year
measure: Incremental Recovery
timeFrame: At 1 hour after the start of infusion
measure: Half-life (t1/2) of rVIII-SingleChain
timeFrame: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
measure: Area Under the Concentration Curve (AUC)
timeFrame: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
measure: Clearance (Cl) of rVIII-SingleChain
timeFrame: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
measure: Number of Subjects With Inhibitor Formation to rVIII-SingleChain
timeFrame: 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).
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Study Site
state: Colorado
city: Chicago
country: United States
facility: Study Site
state: Illinois
city: Melbourne
country: Australia
facility: Study Site
state: Victoria
city: Linz
country: Austria
facility: Study Site
city: Vienna
country: Austria
facility: Study Site
city: Brest
country: France
facility: Study Site
city: Le Kremlin Bicetre
country: France
facility: Study Site
city: Lille Cedex
country: France
facility: Study Site
city: Nantes
country: France
facility: Study Site
city: Paris
country: France
facility: Study Site
city: Tbilisi
country: Georgia
facility: Study Site
city: Bonn
country: Germany
facility: Study Site
city: Bremen
country: Germany
facility: Study Site
city: Frankfurt/Main
country: Germany
facility: Study Site
city: Hannover
country: Germany
facility: Study Site
city: Milano
country: Italy
facility: Study Site
city: Beirut
country: Lebanon
facility: Study Site
city: Kuala Lumpur
country: Malaysia
facility: Study Site
city: Amsterdam
country: Netherlands
facility: Study Site
city: Njmegen
country: Netherlands
facility: Study Site
city: Utrecht
country: Netherlands
facility: Study Site
city: Cebu City
country: Philippines
facility: Study Site
city: Davao City
country: Philippines
facility: Study Site
city: Rzeszow
country: Poland
facility: Study Site
city: Oporto
country: Portugal
facility: Study Site
city: Timisoara
country: Romania
facility: Study Site
city: Madrid
country: Spain
facility: Study Site
city: Lucerne
country: Switzerland
facility: Study Site
city: Bangkok
country: Thailand
facility: Study Site
city: Bangkok
country: Thailand
facility: Study Site
city: Chiang Mai
country: Thailand
facility: Study Site
city: Khon Kaen
country: Thailand
facility: Study Site
city: Songkla
country: Thailand
facility: Study Site
city: Adana
country: Turkey
facility: Study Site
city: Istanbul
country: Turkey
facility: Study Site
city: Izmir
country: Turkey
facility: Study Site
city: Lviv
country: Ukraine
facility: Study Site
Study officials:
affiliation: CSL Behring
name: Program Director
role: STUDY_DIRECTOR
References: