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Pharmacokinetic, Efficacy, and Safety Study of Recombinant Factor VIII Single Chain (rVIII-SingleChain) in Children With Severe Hemophilia A

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ClinicalTrials.gov Identifier: NCT02093897
Recruitment Status : Completed
First Posted : March 21, 2014
Results First Posted : January 27, 2017
Last Update Posted : January 27, 2017
Sponsor:
Information provided by (Responsible Party):
CSL Behring

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.

Condition or disease Intervention/treatment Phase
Congenital Hemophilia A Biological: rVIII-SingleChain Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
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.
Biological: rVIII-SingleChain
Other Names:
  • Recombinant Factor VIII single chain
  • CSL627




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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 ]
  3. Consumption of rVIII-SingleChain - IU/kg Per Subject Per Month [ Time Frame: Up to 1 year ]
  4. Consumption of rVIII-SingleChain - IU/kg Per Subject Per Year [ Time Frame: Up to 1 year ]
  5. Consumption of rVIII-SingleChain - IU/kg Per Bleeding Event [ Time Frame: Up to 1 year ]
  6. Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Month [ Time Frame: Up to 1 year ]
  7. Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Year [ Time Frame: Up to 1 year ]
  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.



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Ages Eligible for Study:   up to 11 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

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


  Show 37 Study Locations
Sponsors and Collaborators
CSL Behring
Investigators
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Study Director: Program Director CSL Behring

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Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT02093897     History of Changes
Other Study ID Numbers: CSL627_3002
2012-001336-65 ( EudraCT Number )
First Posted: March 21, 2014    Key Record Dates
Results First Posted: January 27, 2017
Last Update Posted: January 27, 2017
Last Verified: December 2016
Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants