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 (Alfa-PROTECT)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hemophilia A; Children; Prophylaxis of Bleeding; Treatment of Bleeding
• Intervention / Treatment: Biological: Damoctocog alfa pegol (Jivi, BAY94-9027)

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Bayer Clinical Trials Contact; Phone Number: (+)1-888-84 22937; Email: clinical-trials-contact@bayer.com

Study Locations

• Argentina
  • Buenos Aires
    • La Plata, Buenos Aires, Argentina, 1900
      • Hospital de Niños Sor María Ludovica
  • Mendoza
    • Godoy Cruz, Mendoza, Argentina, 5501
      • Instituo Hematología Arbesú
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000CKF
      • Instituto de Hematología Dr. Rubén Dávoli
• Brazil
  • Multiple Locations, Brazil
    • Many Locations
  • Rio de Janeiro, Brazil, 20211030
    • HEMORIO
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil, 13083-878
      • Hospital das Clínicas de Campinas - UNICAMP
    • Ribeirão Preto, Sao Paulo, Brazil, 14051-140
      • Hosp Clínicas Facult. Med. de Ribeirão Preto / USP
    • São Paulo, Sao Paulo, Brazil, 01223-001
      • Instituto de Pesquisa e Inovação Tecnologica (IPITEC)
• Canada
  • Multiple Locations, Canada
    • Many Locations
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster Children's Hospital
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00165
      • IRCCS Ospedale Pediatrico Bambino Gesu
• Norway
  • Oslo, Norway, 0372
    • OUS Rikshospitalet Klinisk Forskningspost Barn
• Turkey
  • Adana, Turkey, 01130
    • Acibadem Adana Hastanesi
  • Ankara, Turkey, 6100
    • Hacettepe Universitesi Tip Fakultesi
  • Antalya, Turkey, 07059
    • Akdeniz Universitesi Tip Fakultesi Hastanesi
  • Gaziantep, Turkey, 27070
    • Gaziantep Universitesi Tip Fakultesi
  • Izmir, Turkey, 35100
    • Ege Universitesi Tip Fakultesi
  • Multiple Locations, Turkey
    • Many Locations
  • Samsun, Turkey, 55139
    • Ondokuz Mayis Uni Tip Fakultesi
• United States
  • Florida
    • Orlando, Florida, United States, 32806
      • Arnold Palmer Hospital for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Main study (Part A) and the extension study (Part B); Part A will last for 6 months. After completing Part A participants will continue in the extension study for another 18 months.

Biological: Damoctocog alfa pegol (Jivi, BAY94-9027); Part A: 40 IU/kg (up to 60 IU/kg at the investigator's discretion), two times per week (2x/week) with the first 4 infusions under medical supervision. Thereafter, participants will continue their treatment as home treatment. Dose may be increased up to 60 IU/kg if needed at any time during the study at the investigator's discretion. Part B: Each participant may continue on prophylaxis dose regimen as prescribed in part A (40 - 60 IU/kg, 2x per week) or adjustments to prophylaxis dose / dose frequency can be made at the investigator's discretion (based on the bleeding events and individual needs): Dose frequency may be decreased to every 5 days with a prophylaxis dose of 60 IU/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AESI (hypersensitivity and loss of efficacy) associated with the first 4 exposure days leading to discontinuation	AESI = adverse events of special interest	Up to 6 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2022
• Primary Completion (Actual): January 4, 2024
• Study Completion (Estimated): July 10, 2025

Study Registration Dates

• First Submitted: November 24, 2021
• First Submitted That Met QC Criteria: December 3, 2021
• First Posted (Actual): December 7, 2021

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A; Hemorrhage; Coagulants; Factor VIII
• Other Study ID Numbers: 21824; 2021-004858-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No