do_not_disturb_altRecruitment Complete

Treatment of bleeding, Prophylaxis of bleeding, Hemophilia A, Children

A study to learn how safe the study treatment BAY94-9027 is and how it affects the body in previously treated children aged 7 to less than 12 years with severe hemophilia A, a genetic bleeding disorder that is caused by the lack of a protein called clotting factor 8 (FVIII) in the blood

Trial purpose

Researchers are looking for a better way to treat hemophilia A.
Hemophilia A is a genetic disorder where the body does not create enough of a protein called clotting factor 8 (FVIII) present in the blood. People with hemophilia A may bleed for a long time from minor wounds, have painful bleeding into joints, or have internal bleeding. In severe hemophilia A (clotting factor 8 levels less than 1%) bleedings are more likely to happen.
In this study researchers want to learn more about the treatment called BAY94-9027. BAY94-9027 is an injectable medicine used to replace missing clotting factor 8. In BAY94-9027 the clotting factor 8 has been pegylated (combined with a substance called polyethylene glycol (PEG)). This is to make the treatment last longer in the body so that less injections are required. BAY94-9027 is already available for the prevention and treatment of bleeding in adults and children who are 12 years and older. BAY 94-9027 is also called Jivi.
BAY94-9027 is not yet available for children aged 7 to less than 12 years. One potential specific risk of pegylated drugs is that proteins in the blood called antibodies are built. These may attach to the pegylation part of the drug and this in turn may lead to allergic reactions and the drug not working as well as it should during first 4 infusions. In studies that have been done so far, this has been seen in some children younger than six years, but not in 29 children aged 6 to less than 12 years treated with BAY94-9027. Further safety information related to how the body reacts to BAY94-9027 is however still needed for this age group.
The main purpose of this study is to learn how safe BAY94-9027 is (safety) and how it affects the body (tolerability) in previously treated children with severe hemophilia A who are between 7 to less than 12 years. To answer this question, the researchers will study information about two medical problems of special interest, if allergic reactions occur (also called hypersensitivity) and if the drug is not working as well as it should (also called loss of efficacy) during the first 4 infusions.
Allergic reactions may range from mild local reactions to widespread effects such as shortness of breath, skin rashes and low blood pressure. Only allergic reactions related to the study treatment will be considered.
The assessment if loss of efficacy occurred will be based on the occurrence of bleeding, the clotting factor 8 level in blood after injection called recovery, clotting factor 8 inhibitor tests and measurement of antibodies against the PEG.
The study has two parts, A and B. Part A takes 6 months and part B takes 18 months. In part A the participants will receive two injections of BAY94-9027 per week. In part B, the number of injections may be decreased, with up to five days between the injections. The participants in this study will visit the study site around 14 times and will have 15 phone visits. In part A, visit 1 is for screening. Visits 2 to 5 take place twice a week for two weeks. Visit 6 two weeks after visit 5, visits 7 to 10 take place monthly with visit 11 six weeks after visit 10. In part B, site visits will occur on month 9, 12, 18 and 24 and phone calls every month between the site visits. The participants’ and their caregivers will record in an electronic patient diary information about when the study treatment was given and bleeding episodes that have happened.
During the study, the study doctors and their team will
•   take blood samples,
•   do physical examinations,
•   review the participants’ electronic diary
•   ask questions about the participants’ quality of life,
•   ask the participants questions about how they are feeling and what adverse events they are having
An adverse event is a medical problem that happens during the study. Doctors keep track of all adverse events that happen in study, even if they do not think the adverse events might be related to the study treatments.

Key Participants Requirements

Sex

Male

Age

7 - 11 Years
  • - Participants with severe hemophilia A (participant’s own FVIII activity [FVIII:C] <1%)
    - Participants must be previously treated with FVIII concentrate(s) (plasma derived or recombinant) for a minimum of 50 exposure days (EDs) at the time of signing the informed consent
    - Participant has understood the study if appropriate for his age, informed consent must be signed by the parent, the participant can only sign the assent
    - Willingness and ability of participants and/or parents /caregivers to complete training in the use of the electronic patient diary (EPD) and to document infusions during the study
  • - History of FVIII inhibitors
    - Current evidence of inhibitor to FVIII measured using the Nijmegen-modified Bethesda assay (≥0.6 BU/mL) at the time of screening (central laboratory)
    - Any other inherited or acquired bleeding disorder in addition to hemophilia A (e.g. von Willebrand disease, hemophilia B)
    - Known hypersensitivity or allergic reaction to drug substance, excipients or mouse or hamster protein
    - Any other significant medical condition that the investigator feels would be a risk to the patient or would impede the study
    - Requires any pre-medication to tolerate FVIII treatment (e.g. antihistamines)
    - Planned major surgery during the study
    - Any individual who is 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
    - Any individual who received commercially available subcutaneous factor substitution therapy (emicizumab) within the last 6 months
    - The participant is currently participating in another investigational drug study or has participated in a clinical study involving an investigational drug within 30 days of study entry or previous participation in a clinical study with BAY94-9027

Trial summary

Enrollment Goal
33
Trial Dates
March 2022 - May 2025
Phase
Phase 3
Could I Receive a placebo
No
Products
Jivi (Damoctocog, BAY94-9027)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Recruiting
Many LocationsMany Locations, Canada
Not yet recruiting
Many LocationsMany Locations, Turkey
Not yet recruiting
Many LocationsMany Locations, Brazil
Withdrawn
UC Davis Comprehensive Cancer CenterSacramento, 95817, United States
Withdrawn
Rush University Medical CenterChicago, 60612, United States
Withdrawn
University Hospitals Cleveland Medical CenterCleveland, 44106, United States
Withdrawn
Rutgers Robert Wood Johnson Medical SchoolNew Brunswick, 08901, United States
Completed
Arnold Palmer Hospital for ChildrenOrlando, 32806, United States
Withdrawn
Tulane University School of MedicineNew Orleans, 70112, United States
Completed
McMaster Children's HospitalHamilton, L8N 3Z5, Canada
Not yet recruiting
Alberta Children's Hospital - Hematology / Oncology / Blood and Marrow Transplant ClinicCalgary, T3B 6A8, Canada
Completed
Ege Universitesi Tip FakultesiIzmir, 35100, Turkey
Withdrawn
Istanbul Universitesi Istanbul Tip FakultesiIstanbul, 34093, Turkey
Completed
Acibadem Adana HastanesiAdana, 1130, Turkey
Completed
Akdeniz Universitesi Tip Fakultesi HastanesiAntalya, 7059, Turkey
Completed
Hacettepe Universitesi Tip FakultesiAnkara, 6100, Turkey
Active, not recruiting
Ondokuz Mayis Uni Tip FakultesiSamsun, 55139, Turkey
Withdrawn
Health Ministry Of Türkiye Republic Ankara Bilkent City HospitalAnkara, 6800, Turkey
Withdrawn
Necmettin Erbakan Universitesi Meram Tip Fakultesi HastanesiKonya, 42080, Turkey
Completed
Gaziantep Universitesi Tip FakultesiGaziantep, 27070, Turkey
Completed
Irmandadade da Santa Casa de Misericordia de Sao Paulo (iSANTACASA)São Paulo, 01223-001, Brazil
Withdrawn
Centro Estadual de Hemoterapia e Hematologia Marcos Daniel Santos - HEMOESVitória, 29.047-105, Brazil
Active, not recruiting
Hospital das Clínicas de Campinas - UNICAMPCampinas, 13083-878, Brazil
Completed
HEMORIORio de Janeiro, 20211-030, Brazil
Completed
Hosp Clínicas Facult. Med. de Ribeirão Preto / USPRibeirão Preto, 14051-140, Brazil
Withdrawn
Fundação Centro de Hemoterapia e Hematologia do ParáBelém, 66033-000, Brazil
Completed
OUS Rikshospitalet Klinisk Forskningspost BarnOslo, 372, Norway
Completed
AORN Santobono-PausiliponNapoli, 80122, Italy
Completed
Ospedale Pediatrico Bambino Gesù - Oncoematologia, Trapianto Emopoietico e Terapie CellulariRoma (RM), 00165, Italy
Not yet recruiting
Organizacion Medica de Investigacion (OMI)Buenos Aires, C1015ABO, Argentina
Completed
Instituo Hematología ArbesúGodoy Cruz, 5501, Argentina
Active, not recruiting
Instituto de Hematología Dr. Rubén DávoliRosario, S2000CKF, Argentina
Completed
Hospital de Niños Sor María LudovicaLa Plata, 1900, Argentina

Primary Outcome

  • AESI (hypersensitivity and loss of efficacy) associated with the first 4 exposure days leading to discontinuation
    AESI = adverse events of special interest
    date_rangeTime Frame:
    Up to 6 months

Secondary Outcome

  • Adverse drug reactions (ADRs)
    date_rangeTime Frame:
    Up to 6 months
  • Anti-drug antibody (ADA) development
    date_rangeTime Frame:
    Pre-infusion and up to 6 months
  • The number of participants with confirmed Factor VIII inhibitors
    date_rangeTime Frame:
    Pre-infusion and up to 6 months
  • Annualized bleeding rate (ABR)
    date_rangeTime Frame:
    Up to 24 months
  • BAY94-9027 consumption
    date_rangeTime Frame:
    Up to 24 months
  • Number of infusions/month and year (Annualized Infusion Rate)
    date_rangeTime Frame:
    Up to 24 months

Trial design

A phase 3, single group treatment, open-label, study to evaluate the safety of BAY 94-9027 infusions for prophylaxis and treatment of bleeding in previously treated children aged 7 to <12 years with severe hemophilia A
Trial Type
Interventional
Intervention Type
Biological/Vaccine
Trial Purpose
Treatment
Allocation
N/A
Blinding
N/A
Assignment
Single Group Assignment
Trial Arms
1