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Completed

NCT Number: NCT01311648

BAY81-8973 Pediatric Safety and Efficacy Trial

The primary objective was to evaluate the safety and efficacy of the treatment with BAY81-8973 for prophylaxis and treatment of breakthrough bleeds in children with severe hemophilia A.

The secondary objectives were

* To assess the safety and efficacy of BAY81-8973 during surgeries. * To assess incremental recovery of BAY81-8973. * To assess pharmacokinetic (PK) parameters in a subset of children (Previously treated patients [PTPs] and previously untreated patients [PUPs] / minimally treated patients [MTPs] - participation in PK sampling was voluntary and required consent).

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Key information

Conditions

Haemophilia 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

0 year–12 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 3

Primary location

Bahía Blanca, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Male
  • PTPs (previously treated patients): aged <= 12 years
  • PUPs (previously untreated patients) / MTPs (minimally treated patients): aged < 6 years
  • Severe hemophilia A defined as < 1% FVIII concentration (FVIII:C)
  • PTPs: >= 50 exposure days (EDs) with any FVIII concentrate, no current evidence of inhibitory antibody, and no history of FVIII inhibitor formation
  • PUPs: no prior exposure to any FVIII product
  • MTPs: having no more than 3 EDs with any FVIII product, no current evidence of inhibitory antibody and no history of FVIII inhibitor formation

Exclusion criteria

  • With another bleeding disorder that is different from Hemophilia A
  • With thrombocytopenia (platelet count < 100 000/mm^3)
  • Creatinine > 2x upper limit of normal or Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) > 5x upper limit of normal
  • Without a negative inhibitor testing at screening (except for PUPs)
  • Receiving chemotherapy, immune modulatory drugs, has received another investigational FVIII product within the last month, or received another experimental drug within the last 3 months
  • Requires any pre-medication to tolerate FVIII treatment
  • Known hypersensitivity to active substance, mouse, or hamster protein

Treatment and study plan

Recombinant Factor VIII (Kovaltry, BAY81-8973)

Biological

Main study: 25-50 IU/kg at least 2x/week for 6 months and at least 50 EDs, IV infusion; Extension study: 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part A and extension study), IV infusion. Exposure day (ED): An ED is a unit of time (1 day) in which replacement treatment of Hemophilia is given to a patient.

Primary outcomes

  1. Annualized Number of Total Bleeds Within 48 h

    Time frame: Within 48 hours post infusion

    Annualized number (mean +/- standard deviation) of total bleeds that occurred within 48 hours after all prophylaxis infusions (Part A: 6 months and at least 50 exposure days [EDs]; Part B: at least 50 EDs or until inhibitor development) was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').

  2. Annualized Number of Total Bleeds Within 48 h

    Time frame: Within 48 hours post infusion

    Annualized number (median [inter-quartile range (Q1-Q3)]) of total bleeds that occurred within 48 hours after all prophylaxis infusions (Part A: 6 months and at least 50 exposure days [EDs]; Part B: at least 50 EDs or until inhibitor development) was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').

Secondary outcomes

  1. Annualized Number of Total Bleeds During Prophylaxis Treatment

    Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)

    Annualized number (mean +/- standard deviation) of total bleeds that occurred during prophylaxis treatment was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').

  2. Annualized Number of Total Bleeds During Prophylaxis Treatment

    Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)

    Annualized number (median [inter-quartile range (Q1-Q3)]) of total bleeds that occurred during prophylaxis treatment was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').

  3. Hemostatic Control During Major and Minor Surgeries

    Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)

    For participants who underwent major or minor surgeries during the study, hemostasis during the surgeries was assessed as excellent, good, moderate or poor. Number of surgeries per assessment was summarized and reported.

  4. Number of Participants With Inhibitor Development in Main Study

    Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)

    Number of participants with confirmed positive FVIII inhibitor titer (≥ 0.6 Bethesda unit [BU/mL]) during the main study was summarized and classified as participants developing low titer inhibitor (i.e. ≥ 0.6 to ≤ 5.0 BU/mL) and participants developing high titer inhibitor (i.e. > 5.0 BU/mL).

  5. Number of Participants With New Inhibitor Development in Extension Study

    Time frame: From start of extension study to at least 100 cumulative exposure days (EDs) (median 421 EDs; median 3.8 years)

    Number of participants who had not developed an inhibitor during the main study but developed an inhibitor (confirmed positive FVIII inhibitor titer [≥ 0.6 BU/mL]) during the extension study was summarized and classified as participants developing low titer inhibitor (i.e. ≥ 0.6 to ≤ 5.0 BU/mL) and participants developing high titer inhibitor (i.e. > 5.0 BU/mL).

  6. Factor VIII Recovery Values

    Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)

    Incremental recovery of Factor VIII (FVIII) at 20-30 min after end of infusions was determined and mean recovery values were reported.

  7. Consumption of Factor VIII in All Infusions

    Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)

    Factor VIII (FVIII) usage/consumption was summarized for all infusions. Consumption per participant's body weight per year was calculated and reported.

  8. Consumption of FVIII in Infusions for Prophylaxis

    Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)

    Factor VIII (FVIII) usage/consumption was summarized for prophylaxis infusions. Consumption per participant's body weight per year was calculated and reported.

  9. Consumption of FVIII in Infusions for the Treatment of Bleeds

    Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)

    Factor VIII (FVIII) usage/consumption was summarized for infusions used to treat breakthrough bleeds. Consumption per participant's body weight per year was calculated and reported.

  10. Number of Infusions Per Bleed

    Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)

    The number of infusions used to treat a bleed was defined as the first infusion to treat the bleed plus all follow-up infusions to treat the same bleed, if any. The mean value of number of infusions for each bleed was calculated and reported.

  11. Response to Treatment of Bleeds

    Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)

    Participants or caregivers were asked to assess the response to treatment of bleeds as excellent, good, moderate or poor. Percentage of bleeds per assessment was summarized and reported.

  12. Half-life (t1/2) of BAY81-8973 in Plasma

    Time frame: Pre-infusion and until 24 hours post infusion

    Half-life (t1/2) of BAY81-8973 in plasma was measured. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

Sponsors and collaborators

Lead sponsor

Bayer

Industry

Registry information

Official study title

A Multicenter Phase III Uncontrolled Open-label Trial to Evaluate Safety and Efficacy of BAY81-8973 in Children With Severe Hemophilia A Under Prophylaxis Therapy

Important dates

Study start
2011
Primary completion
2019
Study completion
2020
First posted
Mar 9, 2011
Registry last updated
Dec 5, 2023

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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