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

Phase 1

• Conditions: Hemophilia A; MedDRA version: 20.0Level: LLTClassification code 10053753Term: Hemophilia A without inhibitorsSystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2019-004480-48-ES
• Lead Sponsor: Bayer AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-14
• Last Update Posted: 21 December 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Male
• Target Recruitment: 140

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 130
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

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: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluate individual bleeding pattern and bleeding control in hemophilia A patients with clinically severe phenotype treated with FVIII products;Secondary Objective: Collect information on patient-reported outcomes (PROs);Primary end point(s): Number of bleeds (all bleeds) per observation time for each participant (annualized bleeding rate - ABR);Timepoint(s) of evaluation of this end point: Endpoint will be assessed over the course of the study, from enrollment into the study till the completion. The duration per single patient will be between a minimum of 6 months and a maximum of 12 months.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1)Number of spontaneous bleeds per observation time for each participant (ABR)<br>2)Number of treated bleeds per observation time for each participant (ABR)<br>3)FVIII consumption<br>4)Haem-A-QoL (haemophilia quality of life questionnaire) total Score <br>5)Haem-A-QoL domains Physical Health”, Sports and Leisure” <br>6)EQ-5D-5L (The European quality of life-5 dimension-5-level questionnaire) Visual Analogue Scale <br>7)HJHS (haemophilia joint health score) score;Timepoint(s) of evaluation of this end point: 1-3) Endpoints will be assessed over the course of the study, from enrollment into the study till completion. The duration per single patient will be between a minimum of 6 months to a maximum of 12 months.<br>4-6) On day 1.<br>7) At screening, week 26 and End of Study.