check_circleStudy Completed

Haemophilia A

Bayer Identifier:

13400

ClinicalTrials.gov Identifier:

NCT01311648

EudraCT Number:

2010-021781-29

EU CT Number:

Not Available
BAY81-8973 pediatric safety and efficacy trial

Trial purpose

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).

Key Participants Requirements

Sex

Male

Age

0 - 12 Years
  • - 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
  • - 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

Trial summary

Enrollment Goal
94
Trial Dates
June 2011 - October 2020
Phase
Phase 3
Could I Receive a placebo
No
Products
Kovaltry (Antihemophilic Factor [Recombinant], BAY81-8973)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Milano, 20122, Italy
Completed
Padova, 35128, Italy
Completed
Roma, 00165, Italy
Completed
Timisoara, 300011, Romania
Completed
Bucharest, 011026, Romania
Completed
Bucharest, 022328, Romania
Completed
Mohacs, 7700, Hungary
Completed
Debrecen, 4032, Hungary
Completed
Budapest, 1089, Hungary
Completed
Ramat Gan, 5262000, Israel
Completed
Varna, 9010, Bulgaria
Completed
Plovdiv, 4002, Bulgaria
Completed
Vilnius, 08406, Lithuania
Withdrawn
Beograd, 11000, Serbia
Withdrawn
Belgrade, 11000, Serbia
Completed
Wroclaw, 50-368, Poland
Completed
Warszawa, 00-576, Poland
Withdrawn
Malmö, 205 02, Sweden
Withdrawn
Stockholm, 171 76, Sweden
Completed
Riga, LV-1004, Latvia
Withdrawn
Kragujevac, 34000, Serbia
Completed
Lodz, 91-738, Poland
Completed
Århus N, 8200, Denmark
Withdrawn
East Lansing, 48823, United States
Completed
Columbus, 43205-2696, United States
Completed
Toronto, M5G 1X8, Canada
Completed
Edmonton, T6G 2C8, Canada
Completed
Crumlin, 12, Ireland
Completed
Cleveland, 44106, United States
Withdrawn
Louisville, 40202, United States
Completed
Cincinnati, 45229, United States
Withdrawn
Chattanooga, 37403, United States
Completed
New Orleans, 70112, United States
Completed
Cluj-Napoca, 400177, Romania
Withdrawn
Brasov, 500063, Romania
Completed
Hamilton, L8N 3Z5, Canada
Completed
Bari, 70126, Italy
Withdrawn
San Luis Potosí, 78216, Mexico
Completed
Oaxaca, 68000, Mexico
Completed
Guadalajara, 44280, Mexico
Withdrawn
Wien, 1090, Austria
Withdrawn
Innsbruck, 6020, Austria
Withdrawn
Graz, 8036, Austria
Completed
Madrid, 28046, Spain
Completed
A Coruña, 15006, Spain
Completed
Valencia, 46026, Spain
Withdrawn
Barcelona, 08035, Spain
Withdrawn
Buenos Aires, C1425EFD, Argentina
Withdrawn
Chelyabinsk, 454076, Russian Federation
Completed
Kirov, 610027, Russian Federation
Completed
Kazan, 139445, Russian Federation
Withdrawn
La Plata, 1900, Argentina
Completed
Bahía Blanca, B8001HXM, Argentina
Withdrawn
Linz, 4020, Austria
Withdrawn
Liverpool, L12 2AP, United Kingdom
Completed
Esplugues de LLobregat, 8950, Spain
Completed
Volgograd, 400138, Russian Federation
Withdrawn
Resistencia, 3500, Argentina
Withdrawn
Mendoza, M5500GEC, Argentina
Withdrawn
Sofia, 1527, Bulgaria
Completed
San Juan del Río, 76800, Mexico
Completed
Oslo, Norway
Withdrawn
Pachuca, 42070, Mexico
Completed
Cáceres, 10003, Spain
Completed
Alicante, 03010, Spain
Withdrawn
Greenville, 27834, United States
Withdrawn
Charleston, 29425, United States
Withdrawn
Kazan, 420138, Russia
Completed
Catania, 95123, Italy
Withdrawn
San Miguel de Tucumán, 4000, Argentina
Withdrawn
La Plata, 1900, Argentina
Withdrawn
Thessaloniki, 54642, Greece
Withdrawn
Goudi / Athens, 11527, Greece

Primary Outcome

  • Annualized number of total bleeds within 48 h
    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').
    date_rangeTime Frame:
    Within 48 hours post infusion
  • Annualized number of total bleeds within 48 h
    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').
    date_rangeTime Frame:
    Within 48 hours post infusion

Secondary Outcome

  • Annualized number of total bleeds during prophylaxis treatment
    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').
    date_rangeTime 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 of total bleeds during prophylaxis treatment
    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').
    date_rangeTime 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)
  • Hemostatic control during major and minor surgeries
    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.
    date_rangeTime 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 inhibitor development in main study
    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).
    date_rangeTime 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 new inhibitor development in extension study
    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).
    date_rangeTime Frame:
    From start of extension study to at least 100 cumulative exposure days (EDs) (median 421 EDs; median 3.8 years)
  • Factor VIII recovery values
    Incremental recovery of Factor VIII (FVIII) at 20-30 min after end of infusions was determined and mean recovery values were reported.
    date_rangeTime 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)
  • Consumption of Factor VIII in all infusions
    Factor VIII (FVIII) usage/consumption was summarized for all infusions. Consumption per participant's body weight per year was calculated and reported.
    date_rangeTime 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)
  • Consumption of FVIII in infusions for prophylaxis
    Factor VIII (FVIII) usage/consumption was summarized for prophylaxis infusions. Consumption per participant's body weight per year was calculated and reported.
    date_rangeTime 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)
  • Consumption of FVIII in infusions for the treatment of bleeds
    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.
    date_rangeTime 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 infusions per bleed
    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.
    date_rangeTime 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)
  • Response to treatment of bleeds
    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.
    date_rangeTime 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)
  • Half-life (t1/2) of BAY81-8973 in plasma
    Half-life (t1/2) of BAY81-8973 in plasma was measured. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
    date_rangeTime Frame:
    Pre-infusion and until 24 hours post infusion

Trial design

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
Trial Type
Interventional
Intervention Type
Biological/Vaccine
Trial Purpose
Treatment
Allocation
N/A
Blinding
Open Label
Assignment
Single Group Assignment
Trial Arms
2

Additional Information

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