Pharmacokinetic, Efficacy, and Safety Study of Recombinant Factor VIII Single Chain (rVIII-SingleChain) in Children With Severe Hemophilia A
|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 evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02093897|
Recruitment Status : Completed
First Posted : March 21, 2014
Results First Posted : January 27, 2017
Last Update Posted : January 27, 2017
|Condition or disease||Intervention/treatment||Phase|
|Congenital Hemophilia A||Biological: rVIII-SingleChain||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||84 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase III Open-label Pharmacokinetic, Efficacy and Safety Study of rVIII-SingleChain in a Pediatric Population With Severe Hemophilia A|
|Study Start Date :||March 2014|
|Actual Primary Completion Date :||August 2015|
|Actual Study Completion Date :||August 2015|
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.
- Treatment Success [ Time Frame: Up to 1 year ]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.
- Annualized Bleeding Rate [ Time Frame: Up to 1 year ]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.
- Percentage of Bleeding Episodes Requiring 1, 2, 3, or More Than 3 Infusions of rVIII-SingleChain to Achieve Hemostasis. [ Time Frame: Up to 1 year ]
- Consumption of rVIII-SingleChain - IU/kg Per Subject Per Month [ Time Frame: Up to 1 year ]
- Consumption of rVIII-SingleChain - IU/kg Per Subject Per Year [ Time Frame: Up to 1 year ]
- Consumption of rVIII-SingleChain - IU/kg Per Bleeding Event [ Time Frame: Up to 1 year ]
- Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Month [ Time Frame: Up to 1 year ]
- Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Year [ Time Frame: Up to 1 year ]
- Incremental Recovery [ Time Frame: At 1 hour after the start of infusion ]Incremental recovery expressed as (IU/dL)/(IU/kg) corrected for subject's predose plasma FVIII activity measured using the chromogenic substrate assay.
- Half-life (t1/2) of rVIII-SingleChain [ Time Frame: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing. ]Half-life (t1/2) of rVIII-SingleChain, baseline uncorrected; plasma FVIII activity measured using the chromogenic substrate assay.
- Area Under the Concentration Curve (AUC) [ Time Frame: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing. ]AUC to the last sample with quantifiable drug concentration (AUC0-t), baseline uncorrected; plasma FVIII activity measured using the chromogenic substrate assay.
- Clearance (Cl) of rVIII-SingleChain [ Time Frame: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing. ]Clearance (Cl) of rVIII-SingleChain, baseline uncorrected; plasma FVIII activity measured using the chromogenic substrate assay.
- Number of Subjects With Inhibitor Formation to rVIII-SingleChain [ Time Frame: 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). ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02093897
|United States, Colorado|
|Aurora, Colorado, United States, 80045|
|United States, Illinois|
|Chicago, Illinois, United States, 60612|
|Melbourne, Victoria, Australia, 3052|
|Linz, Austria, 4020|
|Vienna, Austria, 1090|
|Brest, France, 29609|
|Le Kremlin Bicetre, France, 94270|
|Lille Cedex, France, 59037|
|Nantes, France, 44093|
|Paris, France, 75015|
|Tbilisi, Georgia, 0177|
|Bonn, Germany, 53127|
|Bremen, Germany, 28177|
|Frankfurt/Main, Germany, 60590|
|Hannover, Germany, 30159|
|Milano, Italy, 20122|
|Beirut, Lebanon, 11072240|
|Kuala Lumpur, Malaysia, 50400|
|Amsterdam, Netherlands, 1105 AZ|
|Njmegen, Netherlands, 6525 GA|
|Utrecht, Netherlands, 3584 CX|
|Cebu City, Philippines, 6000|
|Davao City, Philippines, 8000|
|Rzeszow, Poland, 35-310|
|Oporto, Portugal, 4202-451|
|Timisoara, Romania, 300011|
|Madrid, Spain, 28046|
|Lucerne, Switzerland, 6000|
|Bangkok, Thailand, 10330|
|Bangkok, Thailand, 10700|
|Chiang Mai, Thailand, 50200|
|Khon Kaen, Thailand, 40002|
|Songkla, Thailand, 90110|
|Adana, Turkey, 01330|
|Istanbul, Turkey, 34098|
|Izmir, Turkey, 35100|
|Lviv, Ukraine, 79044|
|Study Director:||Program Director||CSL Behring|