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NCT Number: NCT02093897

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

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.

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Key information

Conditions

Congenital Hemophilia A Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Coagulation Protein Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemophilia A Hemorrhagic Disorders

Age range

Up to 11 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 3

Primary location

Study Site, Melbourne, Victoria, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

rVIII-SingleChain

Biological

Other names: Recombinant Factor VIII single chain, CSL627

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

CSL Behring

Industry

Registry information

Official study title

A Phase III Open-label Pharmacokinetic, Efficacy and Safety Study of rVIII-SingleChain in a Pediatric Population With Severe Hemophilia A

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Mar 21, 2014
Registry last updated
Jan 27, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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