Back to resultsA Post Approval Commitment Study to Gain More Information on How Safe and Effective KOVALTRY is in Chinese Children, Adolescents /Adults With Severe Hemophilia A
Primary Purpose
Hemophilia A
Status
Recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 1
Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 2
Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 3
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia A
Eligibility Criteria
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
Sites / Locations
- Nanfang Hospital, Southern Medical University
- Shenzhen Children's Hospital
- Shijiazhuang General Hospital
- NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School
- 1st Affiliated hospital of Soochow University
- Jiangxi Provincial People's Hospital
- Children's Hospital of Shanxi
- Chengdu Women & Children's Central HospitalRecruiting
- The Children's Hospital Zhengjiang University School of Med.Recruiting
- Beijing Children's Hospital, Capital Medical University
- Peking Union Medical College Hospital CAMS
- Childrens Hospital of ShanghaiRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Part A: PTPs <12 years of age
Part A: PTPs ≥12 to 65 years of age
Part B: PUPs/MTPs <6 years of age
Arm Description
Previously treated severe hemophilia A patients (PTPs) <12 years of age
Previously treated severe hemophilia A patients (PTPs) ≥12 to 65 years of age
Previously untreated/minimally treated severe hemophilia A patients (PUPs/MTPs) <6 years of age
Outcomes
Primary Outcome Measures
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).
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).
Secondary Outcome Measures
Annualized bleeding rate of treated bleeding episodes
Annualized bleeding rate (ABR) of bleeding episodes treated with BAY81-8973 during prophylaxis treatment.
Annualized bleeding rate of target joint bleeding episodes
Annualized bleeding rate (ABR) of target joint bleeding episodes during prophylaxis treatment.
Annualized bleeding rate within 48 hours of previous prophylaxis infusion
Annualized bleeding rate (ABR) of bleeding episodes within 48 hours of previous prophylaxis infusion.
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).
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].
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].
Number of participants without bleeding episodes
Number of participants who report no bleeding event during prophylaxis.
Number of infusions per bleeding episode
Number of infusions of BAY81-8973 needed to achieve hemostasis for a bleeding episode.
Factor VIII usage
BAY81-8973 consumption during the study.
Factor VIII inhibitor development by the Nijmegen Bethesda assay
Number of participants with positive Factor VIII (FVIII) inhibitor test (≥0.6 Bethesda unit [BU]).
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.
Maximum concentration (Cmax) of Kovaltry in plasma
Cmax: Maximum observed drug concentration following an infusion of 50 IU/kg.
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.
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.
Treatment-emergent adverse events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04565236
Brief Title
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
Official Title
A Post Approval Commitment Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of KOVALTRY in Chinese Children, Adolescents /Adults With Severe Hemophilia A
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 22, 2020 (Actual)
Primary Completion Date
September 19, 2028 (Anticipated)
Study Completion Date
September 19, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Part A: PTPs <12 years of age
Arm Type
Experimental
Arm Description
Previously treated severe hemophilia A patients (PTPs) <12 years of age
Arm Title
Part A: PTPs ≥12 to 65 years of age
Arm Type
Experimental
Arm Description
Previously treated severe hemophilia A patients (PTPs) ≥12 to 65 years of age
Arm Title
Part B: PUPs/MTPs <6 years of age
Arm Type
Experimental
Arm Description
Previously untreated/minimally treated severe hemophilia A patients (PUPs/MTPs) <6 years of age
Intervention Type
Biological
Intervention Name(s)
Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 1
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 2
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 3
Intervention Description
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 Outcome Measure Information:
Title
Annualized bleeding rate of all bleeding episodes during prophylaxis treatment
Description
Annualized bleeding rate (ABR) of all bleeding episodes during prophylaxis treatment in previously treated patients (PTPs).
Time Frame
Part A: up to 6 months
Title
Annualized bleeding rate within 48 hours of previous prophylaxis infusion
Description
Annualized bleeding rate (ABR) of bleeding episodes within 48 hours of previous prophylaxis infusion in previously untreated/minimally treated patients (PUPs/MTPs).
Time Frame
Part B: up to 48 hours post-infusion for at least 50 exposure days
Secondary Outcome Measure Information:
Title
Annualized bleeding rate of treated bleeding episodes
Description
Annualized bleeding rate (ABR) of bleeding episodes treated with BAY81-8973 during prophylaxis treatment.
Time Frame
Part A: up to 6 months; Part B: up to at least 50 exposure days
Title
Annualized bleeding rate of target joint bleeding episodes
Description
Annualized bleeding rate (ABR) of target joint bleeding episodes during prophylaxis treatment.
Time Frame
Part A: up to 6 months; Part B: up to at least 50 exposure days
Title
Annualized bleeding rate within 48 hours of previous prophylaxis infusion
Description
Annualized bleeding rate (ABR) of bleeding episodes within 48 hours of previous prophylaxis infusion.
Time Frame
Part A: up to 48 hours post-infusion for 6 months
Title
Annualized bleeding rate of all bleeding episodes during prophylaxis treatment
Description
Annualized bleeding rate (ABR) of all bleeding episodes during prophylaxis treatment in previously untreated/minimally treated patients (PUPs/MTPs).
Time Frame
Part B: up to at least 50 exposure days
Title
Assessment of response to treatment of bleeds
Description
Participants or caregivers assessment to Kovaltry treatment on ISTH 4 point response scale for response to treatment of bleed [excellent, good, moderate or poor].
Time Frame
Part A: up to 6 months; Part B: up to at least 50 exposure days
Title
Number of surgeries based on physician's assessment of adequacy of hemostasis in minor surgery
Description
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].
Time Frame
Part A: up to 6 months; Part B: up to at least 50 exposure days
Title
Number of participants without bleeding episodes
Description
Number of participants who report no bleeding event during prophylaxis.
Time Frame
Part A: up to 6 months; Part B: up to at least 50 exposure days
Title
Number of infusions per bleeding episode
Description
Number of infusions of BAY81-8973 needed to achieve hemostasis for a bleeding episode.
Time Frame
Part A: up to 6 months; Part B: up to at least 50 exposure days
Title
Factor VIII usage
Description
BAY81-8973 consumption during the study.
Time Frame
Part A: up to 6 months; Part B: up to at least 50 exposure days
Title
Factor VIII inhibitor development by the Nijmegen Bethesda assay
Description
Number of participants with positive Factor VIII (FVIII) inhibitor test (≥0.6 Bethesda unit [BU]).
Time Frame
Part A: up to 6 months; Part B: up to at least 50 exposure days
Title
In-vivo recovery
Description
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.
Time Frame
Part A: baseline, Month 2 and Month 6; Part B: baseline and end of study
Title
Maximum concentration (Cmax) of Kovaltry in plasma
Description
Cmax: Maximum observed drug concentration following an infusion of 50 IU/kg.
Time Frame
Part A: pre-infusion and up to 30 minutes post-infusion
Title
Area under the plasma concentration versus time curve (AUC) from zero to infinity after single (first) dose
Description
AUC: The total area under the plasma concentration versus time curve following an infusion of 50 IU/kg.
Time Frame
Part A: pre-infusion and up to 48 hours post-infusion
Title
Half-life (t1/2) of Kovaltry in plasma
Description
t1/2: Terminal half-life is the time the plasma concentration during terminal phase is halved following an infusion of 50 IU/kg.
Time Frame
Part A: pre-infusion and up to 48 hours post-infusion
Title
Treatment-emergent adverse events
Time Frame
Part A: up to 6 months; Part B: up to at least 50 exposure days
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bayer Clinical Trials Contact
Phone
(+) 1-888-8422937
Email
clinical-trials-contact@bayer.com
Facility Information:
Facility Name
Nanfang Hospital, Southern Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510515
Country
China
Individual Site Status
Withdrawn
Facility Name
Shenzhen Children's Hospital
City
Shenzhen
State/Province
Guangdong
ZIP/Postal Code
518017
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Shijiazhuang General Hospital
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
050000
Country
China
Individual Site Status
Completed
Facility Name
NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210008
Country
China
Individual Site Status
Completed
Facility Name
1st Affiliated hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Individual Site Status
Completed
Facility Name
Jiangxi Provincial People's Hospital
City
Nanchang
State/Province
Jiangxi
ZIP/Postal Code
330006
Country
China
Individual Site Status
Completed
Facility Name
Children's Hospital of Shanxi
City
Taiyuan
State/Province
Shanxi
ZIP/Postal Code
030013
Country
China
Individual Site Status
Completed
Facility Name
Chengdu Women & Children's Central Hospital
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610091
Country
China
Individual Site Status
Recruiting
Facility Name
The Children's Hospital Zhengjiang University School of Med.
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310056
Country
China
Individual Site Status
Recruiting
Facility Name
Beijing Children's Hospital, Capital Medical University
City
Beijing
ZIP/Postal Code
100045
Country
China
Individual Site Status
Completed
Facility Name
Peking Union Medical College Hospital CAMS
City
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Completed
Facility Name
Childrens Hospital of Shanghai
City
Shanghai
Country
China
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing 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.
Links:
URL
https://clinicaltrials.bayer.com/
Description
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.
Learn more about this trial
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
We'll reach out to this number within 24 hrs