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

A Post Approval Commitment Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of KOVALTRY 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.

Study Overview

• Status: Completed
• Conditions: Hemophilia A
• Intervention / Treatment: Biological: Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 1; Biological: Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 2; Biological: Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 3

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital CAMS
  • Shanghai, China, TBC
    • Childrens Hospital of Shanghai
  • Beijing
    • Beijing, Beijing, China, 100045
      • Beijing Children's Hospital, Capital Medical University
  • Hangzhou Province
    • Hangzhou, Hangzhou Province, China, 310056
      • The Children's Hospital Zhejiang University School of Med
  • Hebei
    • Shijiazhuang, Hebei, China, 50000
      • Shijiazhuang General Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School
    • Suzhou, Jiangsu, China, 215000
      • 1st Affiliated hospital of Soochow University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Jiangxi Provincial People's Hospital
  • Shanxi
    • Taiyuan, Shanxi, China, 30013
      • Children's Hospital of Shanxi
  • Sichuan
    • Chengdu, Sichuan, China, 610091
      • Chengdu Women & Children's Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: PTPs <12 years of age; Previously treated severe hemophilia A patients (PTPs) <12 years of age	Biological: Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 1; 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.
Experimental: Part A: PTPs ≥12 to 65 years of age; Previously treated severe hemophilia A patients (PTPs) ≥12 to 65 years of age	Biological: Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 2; 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.
Experimental: Part B: PUPs/MTPs <6 years of age; Previously untreated/minimally treated severe hemophilia A patients (PUPs/MTPs) <6 years of age	Biological: Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 3; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Bleeding Rate (ABR) of All Bleeding Episodes During Prophylaxis Treatment in Part A	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.	Up to 6 months
Annualized Bleeding Rate (ABR) of All Bleeding Episodes Within 48 Hours of Previous Prophylaxis Infusion in Part B	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.	Up to 48 hours post-infusion during 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Bleeding Rate (ABR) of All Bleeding Episodes Within 48 Hours of Previous Prophylaxis Infusion in Part A	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.	Up to 48 hours post-infusion during 6 months
Annualized Bleeding Rate (ABR) of All Bleeding Episodes During Prophylaxis Treatment in Part B	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.	Up to 51 exposure days
Number of Infusions Per Bleeding Episode	The mean value of number of infusions for the treatment of one bleed to achieve hemostasis is reported.	Part A: up to 6 months; Part B: up to 51 exposure days
Number of Surgeries Per Physician's Assessment of Adequacy of Hemostasis in Minor Surgery	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.	Part A: up to 6 months; Part B: up to 51 exposure days
FVIII In-vivo Recovery in Part B	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.	At baseline, Visit 6 (ED 20), unscheduled visit and final visit, up to 51 exposure days
Factor VIII Inhibitor Development by the Nijmegen Bethesda Assay	Number of participants who developed a positive Factor VIII (FVIII) inhibitor level (≥0.6 Bethesda unit [BU/mL]) during the study is reported.	Part A: up to 6 months; Part B: up to 51 exposure days
Number of Participants With Treatment-emergent Adverse Events	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.	Part A: up to 6 months; Part B: up to 51 exposure days
FVIII In-vivo Recovery in Part A	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.	At baseline, Month 2 and final visit, up to 6 months
Maximum Observed Concentration of FVIII in Plasma (Cmax) in Part A	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.	at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years
Area Under the Plasma Concentration of FVIII Versus Time Curve From Zero to Infinity (AUC) in Part A	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.	at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years
Half-life (t1/2) of FVIII in Plasma in Part A	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.	at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Without Bleeding Episode	Number of participants who did not experience any bleed during the prophylaxis treatment period or within 48 hours of previous prophylaxis infusion is reported.	During prophylaxis treatment in Part A: up to 6 months; Part B: up to 51 exposure days
Number of Bleeds Per Assessment of Response to Treatment of Bleeds	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.	Part A: up to 6 months; Part B: up to 51 exposure days

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2020
• Primary Completion (Actual): March 15, 2024
• Study Completion (Actual): March 15, 2024

Study Registration Dates

• First Submitted: September 4, 2020
• First Submitted That Met QC Criteria: September 21, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): April 18, 2025
• Last Update Submitted That Met QC Criteria: April 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemophilia A; Coagulants; Factor VIII
• Other Study ID Numbers: 19855; 2021-003537-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes