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Completed

NCT Number: NCT04565236

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

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.

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Key information

Conditions

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 Hemorrhagic Disorders

Age range

0 year–65 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 4

Primary location

Beijing Children's Hospital, Capital Medical University, Beijing, Beijing Municipality, China

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Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

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.

Exclusion criteria

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

Treatment and study plan

Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 1

Biological

25 to 50 IU of Kovaltry per kg body weight given via intravenous (IV) infusion twice weekly, three times weekly, or every other day according to individual requirements for 6 months.

The dose decisions are at the discretion of the investigator.

Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 2

Biological

12 year-old: 25 to 50 IU of Kovaltry per kg body weight given via intravenous (IV) infusion twice weekly, three times weekly, or every other day for 6 months.

>12 year-old: 20 to 40 IU of Kovaltry per kg of body weight given via intravenous (IV) infusion two or three times per week for 6 months.

The dose decisions are at the discretion of the investigator.

Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 3

Biological

15 to 50 IU of Kovaltry per kg body weight (minimum dose: 250 IU) given via intravenous (IV) infusions at least once a week.

The dose decisions are at the discretion of the investigator.

Primary outcomes

  1. Annualized Bleeding Rate (ABR) of All Bleeding Episodes During Prophylaxis Treatment in Part A

    Time frame: Up to 6 months

    Annualized number (mean +/- standard deviation) of all bleeding episodes that occurred during the prophylaxis treatment period is reported for previously treated patients (PTPs). All bleeding episodes: sum of spontaneous bleeds and trauma bleeds exclude bleeding due to surgery.

  2. Annualized Bleeding Rate (ABR) of All Bleeding Episodes Within 48 Hours of Previous Prophylaxis Infusion in Part B

    Time frame: Up to 48 hours post-infusion during 6 months

    Annualized number (mean +/- standard deviation) of all bleeding episodes that occurred within 48 hours of previous prophylaxis infusion is reported for previously untreated/minimally treated patients (PUPs/MTPs). All bleeding episodes: sum of spontaneous bleeds and trauma bleeds exclude bleeding due to surgery.

Secondary outcomes

  1. Annualized Bleeding Rate (ABR) of All Bleeding Episodes Within 48 Hours of Previous Prophylaxis Infusion in Part A

    Time frame: Up to 48 hours post-infusion during 6 months

    Annualized number (mean +/- standard deviation) of all bleeding episodes that occurred within 48 hours of previous prophylaxis infusion is reported for previously treated patients (PTPs). All bleeding episodes: sum of spontaneous bleeds and trauma bleeds exclude bleeding due to surgery.

  2. Annualized Bleeding Rate (ABR) of All Bleeding Episodes During Prophylaxis Treatment in Part B

    Time frame: Up to 51 exposure days

    Annualized number (mean +/- standard deviation) of all bleeding episodes that occurred during the prophylaxis treatment period is reported for previously untreated/minimally treated patients (PUPs/MTPs). All bleeding episodes: sum of spontaneous bleeds and trauma bleeds exclude bleeding due to surgery.

  3. Number of Infusions Per Bleeding Episode

    Time frame: Part A: up to 6 months; Part B: up to 51 exposure days

    The mean value of number of infusions for the treatment of one bleed to achieve hemostasis is reported.

  4. Number of Surgeries Per Physician's Assessment of Adequacy of Hemostasis in Minor Surgery

    Time frame: Part A: up to 6 months; Part B: up to 51 exposure days

    For participants who underwent minor surgeries during the study, investigators were ask to assess the adequacy of hemostasis during the surgeries as excellent, good, moderate or poor. Number of surgeries per assessment is reported.

  5. FVIII In-vivo Recovery in Part B

    Time frame: At baseline, Visit 6 (ED 20), unscheduled visit and final visit, up to 51 exposure days

    Incremental recovery of Factor VIII (FVIII) was determined by collecting blood samples pre-infusion and 15-30 minutes after the end of the infusion. Mean recovery values at different time points are reported.

  6. Factor VIII Inhibitor Development by the Nijmegen Bethesda Assay

    Time frame: Part A: up to 6 months; Part B: up to 51 exposure days

    Number of participants who developed a positive Factor VIII (FVIII) inhibitor level (≥0.6 Bethesda unit [BU/mL]) during the study is reported.

  7. Number of Participants With Treatment-emergent Adverse Events

    Time frame: Part A: up to 6 months; Part B: up to 51 exposure days

    An adverse event (AE) was any untoward medical occurrence in a participant, associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly/birth defect; another medical important serious event as judged by the investigator. AEs or SAEs were considered to be treatment emergent (TEAEs or TESAEs) if they started after the first KOVALTRY infusion and up to 3 days after the last dose.

  8. FVIII In-vivo Recovery in Part A

    Time frame: At baseline, Month 2 and final visit, up to 6 months

    Incremental recovery of Factor VIII (FVIII) was determined by collecting blood samples pre-infusion and 15-30 minutes after the end of the infusion. Mean recovery values at different time points are reported.

  9. Maximum Observed Concentration of FVIII in Plasma (Cmax) in Part A

    Time frame: at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years

    For the assessment, participants were administered a dose of 50 IU/kg KOVALTRY. Participants must have no signs or symptoms of an acute bleeding episode. For participants below 12 years, the evaluation was only performed once at baseline. For adolescents/adult participants 12 years or older, the evaluation was performed twice at baseline and at final visit.

  10. Area Under the Plasma Concentration of FVIII Versus Time Curve From Zero to Infinity (AUC) in Part A

    Time frame: at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years

    For the assessment, participants were administered a dose of 50 IU/kg KOVALTRY. Participants must have no signs or symptoms of an acute bleeding episode. For participants below 12 years, the evaluation was only performed once at baseline. For adolescents/adult participants 12 years or older, the evaluation was performed twice at baseline and at final visit.

  11. Half-life (t1/2) of FVIII in Plasma in Part A

    Time frame: at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years

    For the assessment, participants were administered a dose of 50 IU/kg KOVALTRY. Participants must have no signs or symptoms of an acute bleeding episode. For participants below 12 years, the evaluation was only performed once at baseline. For adolescents/adult participants 12 years or older, the evaluation was performed twice at baseline and at final visit.

Other outcomes

  1. Number of Participants Without Bleeding Episode

    Time frame: During prophylaxis treatment in Part A: up to 6 months; Part B: up to 51 exposure days

    Number of participants who did not experience any bleed during the prophylaxis treatment period or within 48 hours of previous prophylaxis infusion is reported.

  2. Number of Bleeds Per Assessment of Response to Treatment of Bleeds

    Time frame: Part A: up to 6 months; Part B: up to 51 exposure days

    Participants or caregivers were asked to assess the response to treatment of bleeds as excellent, good, moderate or poor. Number of bleeds per assessment is reported.

Sponsors and collaborators

Lead sponsor

Bayer

Industry

Registry information

Official study title

A Post Approval Commitment Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of KOVALTRY in Chinese Children, Adolescents /Adults With Severe Hemophilia A

Important dates

Study start
2020
Primary completion
2024
Study completion
2024
First posted
Sep 25, 2020
Registry last updated
Apr 18, 2025

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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