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

Bayer

Status and phase: Completed; Phase 4

Conditions: Hemophilia A

Treatments: 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

Funder types: Industry

Identifiers

NCT04565236

19855

2021-003537-11 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 45 patients

Sex: Male

Ages: Under 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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45 participants in 3 patient groups

Part A: PTPs <12 years of age

Experimental group

Description:

Previously treated severe hemophilia A patients (PTPs) \<12 years of age

Treatment:

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

Part A: PTPs ≥12 to 65 years of age

Experimental group

Description:

Previously treated severe hemophilia A patients (PTPs) ≥12 to 65 years of age

Treatment:

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

Part B: PUPs/MTPs <6 years of age

Experimental group

Description:

Previously untreated/minimally treated severe hemophilia A patients (PUPs/MTPs) \<6 years of age

Treatment:

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