check_circleStudy Completed

Hemophilia A

Bayer Identifier:

19855

ClinicalTrials.gov Identifier:

NCT04565236

EudraCT Number:

2021-003537-11

EU CT Number:

Not Available
A Post Approval Commitment study to gain more information on how safe and effective KOVALTRY is in Chinese children, adolescents /adults with severe hemophilia A

Trial purpose

The goal of this study is to gather more information on safety and efficacy of Kovaltry for the prevention and treatment of bleeds in Chinese children, adolescents/adults with severe hemophilia A. In addition, pharmacokinetic parameters of Kovaltry will be assessed in a subset of patients.

Key Participants Requirements

Sex

Male

Age

0 - 65 Years
  • Part A (PTPs):
    - Chinese participants with severe hemophilia A (defined as Factor VIII (FVIII): C < 1% with one- stage clotting assay documented at the time of screening)
    - Currently receiving on-demand or any type of prophylaxis treatment regimen with any FVIII product
    - For participants < 12 years of age, ≥ 50 exposure days (ED); for participants ≥ 12 to 65 years of age, ≥ 150 ED with any FVIII product
    - No current evidence of inhibitor
    - No history of FVIII inhibitor formation
    - Signed informed consent

    Part B (PUPs/MTPs):
    - Participants must be <6 years of age at the time of their parent or legal representative’s signature of informed consent on the participant’s behalf
    - Chinese participants with severe hemophilia A (defined as Factor VIII (FVIII): C < 1% with one- stage clotting assay documented at the time of screening)
    - PUPs must have no previous exposure to any FVIII product. MTPs must have no more than 1 ED with any purified FVIII concentrate or 3 exposures with FFP or cryoprecipitate.
    - MTPs must have no current evidence of inhibitor antibody as measured by the Nijmegen-modified Bethesda assay (<0.6 BU/mL) in 2 consecutive samples and must have absence of clinical signs or symptoms of decreased response to FVIII administration. Testing for the 2 negative samples must be performed by the central laboratory at least 1 week but not more than 2 weeks apart. Participants may not receive FVIII product within 72 hours prior to the collection of samples for inhibitor testing.
    - PUPs and MTPs must observe a 6-month washout period if they have received subcutaneous factor substitution therapy (emicizumab).
    - PUPs may be included if they will receive their first FVIII dose with KOVALTRY for treatment of first bleed and agree to start prophylaxis as part of their care. MTPs may be included if they agree to start prophylaxis as part of their care.
  • Part A (PTPs):
    - Any other bleeding disease that is different from hemophilia A (e.g. von Willebrand disease, hemophilia B)
    - Platelet count < 100 000/mm^3
    - Impaired renal function (serum creatinine > 2.0 mg/dL) or active liver disease (alanine aminotransferase/aspartate aminotransferase [ALT/AST] > 5x ULN)
    - Human immunodeficiency virus (HIV) positive with an absolute CD4 lymphocyte cell count < 250 cells/μL
    - Known hypersensitivity to the active substance, mouse or hamster protein
    - Receiving chemotherapy, immune modulatory drugs other than anti-retroviral chemotherapy, or chronic use of oral or intravenous (IV) corticosteroids (> 14 days) within the last 3 months.
    - Requiring any pre-medication to tolerate FVIII infusions (e.g. antihistamines)
    - Currently participating in another investigational drug study, or having previously participated in a clinical study involving an investigational drug within 30 days of signing informed consent or participated in completed interventional clinical studies with BAY81-8973 (Kovaltry)
    - Planned major surgery, defined as surgery with respiratory assistance and/or general anesthesia

    Part B (PUPs/MTPs):
    - Any other bleeding disease that is different from hemophilia A (e.g. von Willebrand disease, hemophilia B)
    - Platelet count < 100 000/mm^3
    - Impaired renal function (serum creatinine >2× upper limit of normal [ULN]) or active liver disease (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >5× ULN) based on screening laboratory assessments
    - MTPs with history of FVIII inhibitor formation
    - Known hypersensitivity to the active substance, mouse or hamster protein
    - First treatment with KOVALTRY for high risk bleeding situations (e.g., surgery, intracranial bleed) or requiring intensive or prolonged treatment
    - Receiving chemotherapy, immune modulatory drugs other than anti-retroviral chemotherapy, or chronic use of oral or intravenous (IV) corticosteroids (> 14 days) within the last 3 months.
    - Requiring any pre-medication to tolerate FVIII infusions (e.g. antihistamines)
    - Currently participating in another investigational drug study, or having previously participated in a clinical study involving an investigational drug within 30 days of signing informed consent or participated in completed interventional clinical studies with BAY 81-8973 (Kovaltry)
    - Planned major surgery, defined as surgery with respiratory assistance and/or general anesthesia
    - Unable to tolerate volume of blood draws required for study participation

Trial summary

Enrollment Goal
45
Trial Dates
September 2020 - March 2024
Phase
Phase 4
Could I Receive a placebo
No
Products
Kovaltry (Antihemophilic Factor [Recombinant], BAY81-8973)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Beijing Children's Hospital, Capital Medical UniversityBeijing, 100045, China
Completed
Children‘s Hospital of ShanxiTaiyuan, 30013, China
Completed
Jiangxi Provincial People’s HospitalNanchang, 330006, China
Withdrawn
Nanfang Hospital, Southern Medical UniversityGuangzhou, 510515, China
Completed
NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med SchoolNanjing, 210008, China
Completed
Peking Union Medical College Hospital CAMSBeijing, 100730, China
Completed
The Children's Hospital Zhejiang University School of MedHangzhou, 310056, China
Completed
1st Affiliated hospital of Soochow UniversitySuzhou, 215000, China
Completed
Chengdu Women & Children's Central HospitalChengdu, 610091, China
Completed
Shijiazhuang General HospitalShijiazhuang, 50000, China
Withdrawn
Shenzhen Children's HospitalShenzhen, 518017, China
Completed
Childrens Hospital of ShanghaiShanghai, TBC, China

Primary Outcome

  • Annualized bleeding rate of all bleeding episodes during prophylaxis treatment
    Annualized bleeding rate (ABR) of all bleeding episodes during prophylaxis treatment in previously treated patients (PTPs).
    date_rangeTime Frame:
    Part A: up to 6 months
  • Annualized bleeding rate within 48 hours of previous prophylaxis infusion
    Annualized bleeding rate (ABR) of bleeding episodes within 48 hours of previous prophylaxis infusion in previously untreated/minimally treated patients (PUPs/MTPs).
    date_rangeTime Frame:
    Part B: up to 48 hours post-infusion for at least 50 exposure days

Secondary Outcome

  • Annualized bleeding rate of treated bleeding episodes
    Annualized bleeding rate (ABR) of bleeding episodes treated with BAY81-8973 during prophylaxis treatment.
    date_rangeTime Frame:
    Part A: up to 6 months; Part B: up to at least 50 exposure days
  • Annualized bleeding rate of target joint bleeding episodes
    Annualized bleeding rate (ABR) of target joint bleeding episodes during prophylaxis treatment.
    date_rangeTime Frame:
    Part A: up to 6 months; Part B: up to at least 50 exposure days
  • Annualized bleeding rate within 48 hours of previous prophylaxis infusion
    Annualized bleeding rate (ABR) of bleeding episodes within 48 hours of previous prophylaxis infusion.
    date_rangeTime Frame:
    Part A: up to 48 hours post-infusion for 6 months
  • Annualized bleeding rate of all bleeding episodes during prophylaxis treatment
    Annualized bleeding rate (ABR) of all bleeding episodes during prophylaxis treatment in previously untreated/minimally treated patients (PUPs/MTPs).
    date_rangeTime Frame:
    Part B: up to at least 50 exposure days
  • Assessment of response to treatment of bleeds
    Participants or caregivers assessment to Kovaltry treatment on ISTH 4 point response scale for response to treatment of bleed [excellent, good, moderate or poor].
    date_rangeTime Frame:
    Part A: up to 6 months; Part B: up to at least 50 exposure days
  • Number of surgeries based on physician’s assessment of adequacy of hemostasis in minor surgery
    Physician’s assessment of participant's hemostatic response to Kovaltry treatment on the ISTH 4 point response scale for adequacy of hemostasis for surgical procedures [excellent, good, moderate or poor].
    date_rangeTime Frame:
    Part A: up to 6 months; Part B: up to at least 50 exposure days
  • Number of participants without bleeding episodes
    Number of participants who report no bleeding event during prophylaxis.
    date_rangeTime Frame:
    Part A: up to 6 months; Part B: up to at least 50 exposure days
  • Number of infusions per bleeding episode
    Number of infusions of BAY81-8973 needed to achieve hemostasis for a bleeding episode.
    date_rangeTime Frame:
    Part A: up to 6 months; Part B: up to at least 50 exposure days
  • Factor VIII usage
    BAY81-8973 consumption during the study.
    date_rangeTime Frame:
    Part A: up to 6 months; Part B: up to at least 50 exposure days
  • Factor VIII inhibitor development by the Nijmegen Bethesda assay
    Number of participants with positive Factor VIII (FVIII) inhibitor test (≥0.6 Bethesda unit [BU]).
    date_rangeTime Frame:
    Part A: up to 6 months; Part B: up to at least 50 exposure days
  • In-vivo recovery
    In-vivo recovery (or incremental recovery) is defined as the increase in the circulating FVIII activity level for one unit (IU) of the FVIII product per kilogram body weight.
    date_rangeTime Frame:
    Part A: baseline, Month 2 and Month 6; Part B: baseline and end of study
  • Maximum concentration (Cmax) of Kovaltry in plasma
    Cmax: Maximum observed drug concentration following an infusion of 50 IU/kg.
    date_rangeTime Frame:
    Part A: pre-infusion and up to 30 minutes post-infusion
  • Area under the plasma concentration versus time curve (AUC) from zero to infinity after single (first) dose
    AUC: The total area under the plasma concentration versus time curve following an infusion of 50 IU/kg.
    date_rangeTime Frame:
    Part A: pre-infusion and up to 48 hours post-infusion
  • Half-life (t1/2) of Kovaltry in plasma
    t1/2: Terminal half-life is the time the plasma concentration during terminal phase is halved following an infusion of 50 IU/kg.
    date_rangeTime Frame:
    Part A: pre-infusion and up to 48 hours post-infusion
  • Treatment-emergent adverse events
    date_rangeTime Frame:
    Part A: up to 6 months; Part B: up to at least 50 exposure days

Trial design

A Post Approval Commitment study to evaluate the efficacy, safety, and pharmacokinetics of KOVALTRY in Chinese children, adolescents /adults with severe hemophilia A
Trial Type
Interventional
Intervention Type
Biological/Vaccine
Trial Purpose
Treatment
Allocation
Non-randomized
Blinding
N/A
Assignment
Single Group Assignment
Trial Arms
3

Additional Information

Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.