A prospective, lead-in study to collect bleeding episodes, Factor VIII (FVIII) infusions, and patient-reported outcomes in patients with hemophilia A

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 13

Inclusion Criteria

- Participant must be *18 years of age at the time of signing the informed
consent.
- Patients with severe hemophilia A (FVIII:C *1% baseline FVIII activity
[FVIII:C] as determined by measurement at the time of screening or from
reliable prior documentation in clinical records of the patients).
- Male.
- Previously treated with FVIII concentrate(s) (plasma derived or recombinant)
for a minimum of 150 exposure days (ED) as documented in reliable prior
clinical records of the patients.
- On regular prophylaxis with FVIII (defined as * 45 weeks/year of treatment
with an adequate dose as per label ) and on stable treatment for at least 6
months as documented in reliable prior clinical records of the patients
- Well-managed patients with at least 1 documented visit at the hemophilia
treatment center in the year prior to enrollment.
- Willing to participate in the interventional Phase 3 gene therapy study with
BAY2599023.
- Capable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in
this protocol.

Exclusion Criteria

Participants are excluded from the study if any of the following criteria
apply. Exclusion criteria marked with an asterisk (*) will lead to exclusion of
the participant from the subsequent Phase 3 study, if occurring at any time
during the lead-in study. If the criteria marked with an asterisk are met
during the study, the participant will withdraw from the study.

Medical Conditions:
- *Current inhibitor to FVIII with a titer * 0.6 BU, confirmed by more than 1
test.
- History of inhibitor with a titer >1.0 BU (as documented in reliable prior
clinical records of the patients) or with a repeated titer 0.6 to <1.0 BU in
more than one subsequent occasion.
- *Significant underlying liver disease, as evidenced by any of the following:
portal hypertension, splenomegaly, ascites, esophageal varices, hepatic
encephalopathy,
reduction below normal limits of serum albumin or an advanced liver disease
(Child-Pugh Grade B and C), suspicion of liver malignancy or fibrosis by
ultrasound / Fibroscan.
- Any of the following:
-- Hemoglobin <;11 g/dL
-- Platelets <100,000 cells/µL
-- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5× ULN
-- Alkaline phosphatase (AP)>2.5 × ULN
-- Total bilirubin >1.5 × ULN
-- Prothrombin time (PT) or international normalized ratio (INR)>1.0 × ULN
-- Creatinine>1.5 mg/dL
- Another bleeding disorder that is different from hemophilia A (e.g., von
Willebrand disease, hemophilia B)
- *Active hepatitis B or C infection, as reflected by HBsAg or HCV-RNA viral
load positivity
- Serological evidence of active HIV-1 or HIV-2 as measured by CD4+ cell count
<200 cells/mm3 and/or viral load >50 gc/mL.
- *Pre-existing immunity against AAVhu37.
- *Any current diagnosis of malignancy.
- Known or suspected autoimmune diseases requiring immunosuppressive therapy.
- Body mass index >; 35 kg/m^2.
- Contraindication for corticosteroid treatment.
- *Any other significant medical condition that would be a risk to the patient
or would affect patient*s ability to receive gene transfer following completion
of his participation in this lead-in study.

Prior/Concomitant Therapy
Listed therapies/medications are not allowed at enrollment, during the study
and will also not allow transition to the Phase 3 study if introduced during
the lead-in study:
- Antiviral therapy for hepatitis B or C ,
- Pre-medication to tolerate FVIII treatment,
- Immunomodulatory drugs (other than corticosteroids),
- Efavirenz,
- Emicizumab,
- Planned major surgery.

Prior/Concurrent Clinical Study Experience
- Participation in any investigational hemophilia product study within 3 months
before screening (participation in any other investigational product study will
not be allowed throughout the study).
- Has received the same or another gene therapy product.

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Outcome Measures:<br /><br>Evaluate individual bleeding pattern and bleeding control in hemophilia A<br /><br>patients with clinically severe phenotype treated with FVIII products.<br /><br>Number of bleeds (all bleeds) per observation time for each participant<br /><br>(annualized bleeding rate (ABR)) [ Time Frame: Endpoint will be<br /><br>assessed over the course of the study, from enrollment into the study till the<br /><br>completion. The duration per single patient will be between a<br /><br>minimum of 6 months to a maximum of 12 months.</p><br>

Secondary Outcome Measures