Hemophilia APhase 4NCT04565236
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 Phase 4 study testing Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 1, Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 2 and Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 3 in people with Hemophilia A, run by Bayer at 10 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 65 years, men only
- Conditions the study is for
- Hemophilia A
- What is being tested?
- Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 1, Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 2 and Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 3
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 10 sitesChina
- Study dates
- 22 Sep 2020to 15 Mar 2024
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 65 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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 locations and contacts
10 sites in 1 country.
10 sites in 1 country
China10 sites
Beijing Children's Hospital, Capital Medical University
Beijing, Beijing Municipality, 100045
Peking Union Medical College Hospital CAMS
Beijing, 100730
Chengdu Women & Children's Central Hospital
Chengdu, Sichuan, 610091
The Children's Hospital Zhejiang University School of Med
Hangzhou, Hangzhou Province, 310056
Jiangxi Provincial People's Hospital
Nanchang, Jiangxi, 330006
NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School
Nanjing, Jiangsu, 210008
Childrens Hospital of Shanghai
Shanghai, TBC
Shijiazhuang General Hospital
Shijiazhuang, Hebei, 50000
1st Affiliated hospital of Soochow University
Suzhou, Jiangsu, 215000
Children's Hospital of Shanxi
Taiyuan, Shanxi, 30013
About this study
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
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.
- Conditions
- Hemophilia A
- Being tested
- 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
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 1Biological
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 2Biological
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 3Biological
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.
| Study group | Role | What they receive |
|---|---|---|
| Part A: PTPs <12 years of age | Experimental | Previously treated severe hemophilia A patients (PTPs) <12 years of age Receives: Biological: Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 1 |
| Part A: PTPs ≥12 to 65 years of age | Experimental | Previously treated severe hemophilia A patients (PTPs) ≥12 to 65 years of age Receives: Biological: Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 2 |
| Part B: PUPs/MTPs <6 years of age | Experimental | Previously untreated/minimally treated severe hemophilia A patients (PUPs/MTPs) <6 years of age Receives: Biological: Recombinant Factor VIII (Kovaltry, BAY81-8973) Treatment Group 3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 48 hours post-infusion during 6 months
Secondary outcomes (11)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: at baseline for PTPs < 12 Years and at baseline and final visit (month 6) for PTPs >= 12 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2020
- Study start22 Sep 2020
- Primary completion15 Mar 2024
- Study completion15 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04565236
- Sponsor's protocol ID
- 19855
- Other IDs
- 2021-003537-11
- Status last verified
- Apr 2025
- First submitted
- 4 Sep 2020
- Last updated
- 18 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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.