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

NCT04565236 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: 198552021-003537-11
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 10

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.

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• Annualized Bleeding Rate (ABR) of All Bleeding Episodes Within 48 Hours of Previous Prophylaxis Infusion in Part A

  Up to 48 hours post-infusion during 6 months

• Annualized Bleeding Rate (ABR) of All Bleeding Episodes During Prophylaxis Treatment in Part B

  Up to 51 exposure days

• Number of Infusions Per Bleeding Episode

  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

  Part A: up to 6 months; Part B: up to 51 exposure days

• FVIII In-vivo Recovery in Part B

  At baseline, Visit 6 (ED 20), unscheduled visit and final visit, up to 51 exposure days

Other Outcomes (2)

• Number of Participants Without Bleeding Episode

  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

  Part A: up to 6 months; Part B: up to 51 exposure days

Study Arms (3)

Part A: PTPs <12 years of age

EXPERIMENTAL

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

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

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

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

Interventions

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

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.

Part A: PTPs <12 years of age

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

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.

Part A: PTPs ≥12 to 65 years of age

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

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.

Part B: PUPs/MTPs <6 years of age

Eligibility Criteria

• Age: 0 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (10)

Beijing Children's Hospital, Capital Medical University

Beijing, Beijing Municipality, 100045, China

Location

The Children's Hospital Zhejiang University School of Med

Hangzhou, Hangzhou Province, 310056, China

Location

Shijiazhuang General Hospital

Shijiazhuang, Hebei, 50000, China

Location

NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School

Nanjing, Jiangsu, 210008, China

Location

1st Affiliated hospital of Soochow University

Suzhou, Jiangsu, 215000, China

Location

Jiangxi Provincial People's Hospital

Nanchang, Jiangxi, 330006, China

Location

Children's Hospital of Shanxi

Taiyuan, Shanxi, 30013, China

Location

Chengdu Women & Children's Central Hospital

Chengdu, Sichuan, 610091, China

Location

Peking Union Medical College Hospital CAMS

Beijing, 100730, China

Location

Childrens Hospital of Shanghai

Shanghai, TBC, China

Location

Related 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.

MeSH Terms

Conditions

Hemophilia A

Interventions

Factor VIII; F8 protein, human

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Limitations and Caveats

Results of ABR of treated/target joint bleeding episodes and FVIII usage are not reported as they are other pre-defined endpoints per protocol.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2020
• First Posted: September 25, 2020
• Study Start: September 22, 2020
• Primary Completion: March 15, 2024
• Study Completion: March 15, 2024
• Last Updated: April 18, 2025
• Results First Posted: April 18, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (10)