Study to test the safety and how well patients with severe hemophilia A respond to treatment with BAY 2599023 (DTX 201), a drug therapy that delivers a healthy version of the defective Factor VIII gene into the nucleus of liver cells using an altered, non-infectious virus (AAV) as a shuttle”.
- Conditions
- Hemophilia AMedDRA version: 20.0Level: LLTClassification code 10060612Term: Hemophilia ASystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2017-000806-39-DE
- Lead Sponsor
- Bayer AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 30
• Males = 18 years of age
• Subjects with severe hemophilia A (baseline FVIII activity FVIII:C <1%) determined by measurement at the time of Screening (unless there is genetic testing compatible with severe deficiency)
• Previously treated with FVIII concentrate(s) (plasma derived or recombinant) or cryoprecipates for a minimum of 150 exposure days (ED)
• Are on one of the following therapies: Prophylaxis, and is willing to stop prophylactic treatment at specified time points throughout the study or On-demand: have had > 4 bleeding events in the last 52 weeks
• Subjects must agree to use double barrier and effective contraception methods. Vasectomized subjects must agree to use condoms. This is
applicable from the time of the study drug administration until notified by the investigator. Time until discontinuation of contraception will be at a minimum 6 months, and will progressively increase with increasing dose. Recommendation to investigators is to continue the
contraception until three consecutive blood and semen samples BLOD of shed virus have been obtained.
Acceptable methods of contraception include, but are not limited to, (i) condoms with a spermicidal agent (ii) diaphragm or cervical cap with
spermicide; if an intra-uterine device or hormone-based contraception is used by the patient's partner, an additional barrier method must be used.
• Male subjects must agree not to donate cells, semen, blood, tissue or organs from the time of study drug administration
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 28
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2
• Current evidence of inhibitor to FVIII with a titer = 0.6 BU/mL
• History of inhibitor to FVIII with a titer = 0.6 BU, or clinical history requiring modification of treatment, suggestive of inhibitor. Family history of inhibitors will not exclude the subject.
• Have 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 a liver biopsy with evidence of stage 3 fibrosis
• 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; Serum creatinine >1.5 mg/dL
• Any individual with another bleeding disorder that is different from hemophilia A (e.g., von Willebrand disease, hemophilia B)
• Have active hepatitis B or C infection, as reflected by HBsAg or HCV-RNA viral load positivity
• Currently on antiviral therapy for hepatitis B or C.
• Serological evidence of active HIV-1 or HIV-2 as measured by CD4+ cell count <200 cells/mm3 and a viral load >50 gc/mL
• Anti-AAVhu37 neutralizing antibody titer =1:5
• Any major and/or orthopedic surgery within screening period prior to trial product administration, and at least 6 months thereafter
• History of a malignancy for which the subject has received treatment in the past 2 years except for prostate cancer being monitored without medical intervention, or surgically removed non-melanoma skin cancer
• Known or suspected autoimmune diseases
• Known prior history of hypersensitivity or anaphylaxis associated with any FVIII or immunoglobulin administration.
• Known or suspected hypersensitivity or allergic reaction to trial product(s) or related FVIII products or any component of BAY 2599023 (DTX201), or a contraindication to prednisolone (as of amendment 6)
• Live vaccines and COVID-19 vaccines are not allowed within the last 30 days prior to the study drug administration; live vaccines may be re-introduced after viral shedding has been cleared
• Subjects on treatment with immunomodulatory agents within the last 3 months prior to study entry or during the study
• Any individual who requires any pre-medication to tolerate FVIII treatment (e.g., antihistamines)
• Prior use of emicizumab within 3 months before dosing
• Clinically relevant findings in the physical examination considered critical by the treating physician, including obesity with BMI > 35 kg/m2
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Investigate the safety and tolerability of single ascending intravenous (IV) doses of BAY 2599023 (DTX201) in adult patients with severe hemophilia A, who have been previously treated with FVIII product;Secondary Objective: Identify a dose of BAY 2599023 (DTX201) that will achieve sustained expression of vector-derived B-domain deleted human factor VIII above 5% at 6 months and 12 months following an IV administration;Primary end point(s): Incidence of adverse events, treatment-emergent adverse events, serious adverse events and Adverse events/serious adverse events of special interest;Timepoint(s) of evaluation of this end point: End points will be assessed over the course of part A and Part B of the study.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Expression pattern of FVIII activity.<br>2. Proportion of patients in the respective dose step, that reached an expression of FVIII above 5% at 6 months and 12 months following the<br>IV administration of BAY2599023;Timepoint(s) of evaluation of this end point: at 6 months & 12 months following an IV administration