A Post Approval Commitment study to evaluate the efficacy, safety, and pharmacokinetics of KOVALTRY in Chinese children, adolescents/adults with severe hemophilia A.

Phase 1

• Conditions: KOVALTRY, indicated for use in adults and children with hemophilia A (congenital Factor VIIIdeficiency) for:- Routine prophylaxis to reduce the frequency of bleeding episodes- On-demand treatment and control of bleeding episodes- Perioperative management of bleeding; MedDRA version: 20.0Level: LLTClassification code 10060612Term: Hemophilia ASystem Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 20.0Level: LLTClassification code 10071818Term: Bleeding prophylaxisSystem Organ Class: 10042613 - Surgical and medical procedures; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2021-003537-11-Outside-EU/EEA
• Lead Sponsor: Bayer Healthcare Company Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2024-03-14
• Last Update Posted: 18 March 2024

Recruitment & Eligibility

• Status: A
• Sex: Male
• Target Recruitment: Not specified

Inclusion Criteria

Part A (PTPs):
Participants are eligible to be included if all of the following criteria apply:
1. Participants enrolled as children must be <12 years at the time of their parent or legal representative’s signature of informed consent on participant’s behalf, or if enrolled as adolescents/adults, must be = age 12 to 65 years at time of signed informed consent.
2. Chinese participants with severe hemophilia A (defined as FVIII:C <1% with one-stage clotting assay documented at the time of screening). If screening results show FVIII:C as equal to or higher than 1%, then severe hemophilia A may be confirmed by documented historical evidence from a (certified) clinical laboratory demonstrating <1% FVIII:C as determined by a one-stage clotting assay.
3. Currently receiving on-demand or any type of prophylaxis treatment regimen with any FVIII product (excluding treatment with fresh-frozen plasma and cryo-precipitate).
4. For participants <12 years of age, =50 exposure days (ED); for participants =12 to 65 years of age, =150 ED with any Factor VIII product (excluding treatment with fresh-frozen plasma and cryo-precipitate).
5. No current evidence of inhibitor antibody as measured by the Nijmegen-modified Bethesda assay [<0.6 Bethesda units (BU)/mL] in 2 consecutive samples and absence of clinical signs or symptoms of decreased response to FVIII administration. (First negative sample can be historical if obtained within 3 months prior to screening with a result of <0.6 BU/mL by classical Bethesda assay. The testing for a second negative, confirmatory sample must, in all cases, be performed by a central laboratory using the Nijmegen-modified Bethesda test. If a first recent sample is not available,
then testing for 2 negative samples must be performed by central laboratory at least 1 week apart). Participants may not receive FVIII within 72 hours prior to the collection of samples for inhibitor testing.
6. No history of FVIII inhibitor formation. Documentation of negative result in medical records is required (Nijmegen-modified Bethesda assay or classical Bethesda assay); participants with a maximum historical titer of 1.0 BU/mL on no more than 1 occasion with classical Bethesda assay but at least 3 successive negative results (<0.6 BU/mL) thereafter are eligible.
7. Male participants only
8. signed informed consent
Other
9. Willingness and ability of participants, parents, or caregiver to comply with prophylaxis schedule and complete training on use of the study electronic patient diary (EPD) and to use the diary to document bleeding and infusion information during the study.

Part B (PUPs/MTPs):
Participants are eligible to be included if all of the following criteria apply:
1. 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.
Type of Participant and Disease Characteristics
2. Chinese participants with severe hemophilia A (defined as FVIII:C <1% with one-stage clotting assay documented at the time of screening). If screening results show FVIII:C as equal to or higher than 1%, then severe hemophilia A may be confirmed by documented historical evidence from a (certified) clinical laboratory demonstrating FVIII:C <1% as determined by a one-stage clotting assay.
3. PUPs must have no previous exposure to any FVIII product. MTPs must have no more than 3 EDs with any FVIII product including FFP,
cryoprecipitate, purified FVIII concentrate and recombin

Exclusion Criteria

Part A (PTPs) Exclusion Criteria
Participants are excluded from Part A of the study if any of the following criteria apply:
Medical Conditions
1. Any other bleeding disease that is different from hemophilia A (e.g., von Willebrand
disease, hemophilia B).
2. Platelet count <100 000/mm3 based on screening laboratory assessments.
3. Impaired renal function (serum creatinine >2.0 mg/dL) or active liver disease (alanine
aminotransferase/aspartate aminotransferase [ALT/AST] >5x ULN) based on
screening laboratory.
4. Human immunodeficiency virus (HIV) positive with an absolute CD4 lymphocyte cell
count <250 cells/µL.
5. Known hypersensitivity to the active substance, mouse or hamster protein.
Prior/Concomitant Therapy
6. Receiving chemotherapy or immune modulatory drugs (e.g., intravenous [IV]
immunoglobulin, cyclosporine) other than anti-retroviral chemotherapy or chronic use
of oral or intravenous (IV) corticosteroids (>14 days) within the last 3 months. Brief
courses of prednisone/methylprednisolone (<14 days) for treatment of disorders such
as synovitis, asthma, etc. are allowed at the discretion of the treating physician
7. Requiring any pre-medication to tolerate FVIII infusions (e.g., antihistamines).
Prior/Concurrent Clinical Study Experience
8. 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).
Other Exclusions
9. Unwilling to comply with study visits or other protocol requirements or is not suitable
for participation in this study for any reason, according to the Investigator.
10. Planned major surgery, defined as surgery with respiratory assistance and/or general
anesthesia.
11. Close affiliation with the investigational site; e.g., a close relative of the investigator,
dependent person (e.g., employee or student of the investigational site).

Part B (PUPs/MTPs) Exclusion Criteria
Participants are excluded from Part B of the study if any of the following criteria apply:
Medical Conditions
1. Any other bleeding disorder that is different from hemophilia A (e.g., von Willebrand
disease, hemophilia B).
2. Platelet count <100 000/mm3 based on screening laboratory assessments.
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.
4. MTPs with history of FVIII inhibitor formation.
5. Known hypersensitivity to the active substance, mouse or hamster protein.
6. First treatment with KOVALTRY for high risk bleeding situations (e.g., surgery,
intracranial bleed etc.) or requiring intensive or prolonged treatment.
7. Planned major surgery, defined as surgery with respiratory assistance and/or general
anesthesia
Prior/Concomitant Therapy
8. Receiving chemotherapy or immune modulatory drugs (e.g., IV immunoglobulin,
cyclosporine) other than anti-retroviral chemotherapy or chronic use (>14 days) of
oral or IV corticosteroids within the last 3 months. Brief courses (<14 days) of
prednisone/methylprednisolone for treatment of disorders such as synovitis, asthma,
etc. are allowed at the discretion of the treating physician.
9. Requiring any pre-medication to tolerate FVIII infusions (e.g., antihistamines).
Prior/Concurrent Clinical Study Experience
10. Cur

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified