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

Phase 3

Completed

Conditions: Prophylaxis of Bleeding
Hemophilia A
Treatment of Bleeding
Children

Interventions: Biological: Damoctocog alfa pegol (Jivi, BAY94-9027)

Registration Number: NCT05147662

Lead Sponsor: Bayer

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 36

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Main study (Part A) and the extension study (Part B)	Damoctocog alfa pegol (Jivi, BAY94-9027)	Part A will last for 6 months. After completing Part A participants will continue in the extension study for another 18 months.

Primary Outcome Measures

Name	Time	Method
Adverse Events of Special Interest (AESI) Hypersensitivity and Loss of Efficacy Associated With the First 4 Exposure Days (EDs) Leading to Discontinuation	Individual first 4 exposure days	The occurrence of the defined adverse events of special interest was documented during the first 4 days that a participant was exposed to the study intervention.

Secondary Outcome Measures

Name	Time	Method
Adverse Drug Reactions (ADRs)	Up to 24 months	Adverse drug reactions were defined as any adverse events where a causal relationship of at least possibly related with the use of BAY 94-9027 had been ascribed by the investigator. In this study, treatment emergent study drug-related adverse events were used in defining ADRs.
Anti-drug Antibody (ADA) Development	Up to 24 months	All participants were tested for the development of anti-drug antibodies (ADAs) (anti-polyethylene glycol \[PEG\] and anti-PEG immunoglobulin M \[IgM\]).
The Number of Participants With Confirmed Factor VIII Inhibitors	Up to 24 months	A positive FVIII inhibitor test was defined with a threshold of ≥ 0.6 BU/mL at the central laboratory. The first positive measurement was confirmed by a second, different sample.
Annualized Bleeding Rate (ABR)	Up to 24 months	For each participant, the number of bleeds was related to the individual observation period to assess bleeding rates. For descriptive analyses, bleeding rates were annualized at the individual participant level using the formula: ABR = (number of bleeds × 365.25 × 24 × 60)/(Period). Period was defined as the number of minutes calculated from the date and time of the beginning of the treatment period and the date and time of the end of the treatment period of interest.
BAY94-9027 Consumption	Up to 24 months	Summary statistics for BAY 94-9027 consumption are provided for prophylaxis treatment, for treatment of bleeds, and overall. Consumption per year and per infusion is presented based on total dose (IU) and dose per body weight (IU/kg).
Number of Infusions/Month and Year (Annualized Infusion Rate)	Up to 24 months	Number of infusions per month and year

Trial Locations

Locations (21): Acibadem Adana Hastanesi, Çocuk Sagligi ve Hastaliklari, Çocuk Hematoloji-Onkoloji Bölümü
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Adana, Turkey
Hacettepe Üniversitesi Tip Fakültesi, Hacettepe Ihsan Dogramaci Çocuk Hastanesi,
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Ankara, Turkey
Gaziantep Üniversitesi Tip Fakültesi, Sahinbey Arastirma Ve Uygulama Hastanesi, Çocuk Hematoloji ve Onkoloji Bilim Dali
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Gaziantep, Turkey
Ege Üniversitesi Tip Fakültesi, Çocuk Sagligi ve Hastaliklari Anabilim Dali, Çocuk Hematoloji Bilim Dali
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Izmir, Turkey
Ondokuz Mayis Üniversitesi Tip Fakültesi, Saglik Uygulama ve Arastirma Merkezi, Çocuk Sagligi ve Hastaliklari Anabilim Dali
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Samsun, Turkey
Arnold Palmer Hospital for Children
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Orlando, Florida, United States
Hospital de Niños Sor María Ludovica
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La Plata, Buenos Aires, Argentina
Organizacion Medica de Investigacion (OMI)
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Buenos Aires, Ciudad Auton. De Buenos Aires, Argentina
Instituo Hematología Arbesú
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Godoy Cruz, Mendoza, Argentina
Instituto de Hematología Dr. Rubén Dávoli
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Rosario, Santa Fe, Argentina
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Acibadem Adana Hastanesi, Çocuk Sagligi ve Hastaliklari, Çocuk Hematoloji-Onkoloji Bölümü
🇹🇷Adana, Turkey