A phase III trial investigating a gene therapy (AAV-hFIXco-Padua, AMT-061), in adult patients with severe or moderately severe haemophilia B, to firstly evaluate if it's effective, and secondly further describe it's safety profile.
- Conditions
- Hemophilia BMedDRA version: 20.0Level: LLTClassification code 10018939Term: Haemophilia B (Factor IX)System Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2017-004305-40-BE
- Lead Sponsor
- CSL Behring LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 75
- Male
- Age =18 years
- Subjects with congenital hemophilia B with known severe or moderately severe factor IX deficiency (=2% of normal circulating factor IX ) for which the subject is on continuous routine factor IX prophylaxis (continuous routine prophylaxis is defined as the intent of treating with an a priori defined frequency of infusions [e.g., twice weekly, once every two weeks, etc.] as documented in the medical records).
- >150 previous exposure days of treatment with factor IX protein
- Have been on stable prophylaxis for at least 2 months prior to screening
- Have demonstrated capability to independently, accurately and in a timely manner complete the diary during the lead-in phase as judged by the investigator
- Acceptance to use a condom during sexual intercourse in the period from IMP administration until AAV5 has been cleared from semen, as evidenced by the central laboratory from negative analysis results for at least 3 consecutively collected semen samples (this criterion is applicable also for subjects who are surgically sterilized)
- Able to provide informed consent following receipt of verbal and written information about the trial.
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 63
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12
- History of factor IX inhibitors
- Positive factor IX inhibitor test at screening and Visit L-Final (based on local laboratory results)
- Screening and Visit L-Final laboratory values (based on central laboratory results):
a. ALT >2 times upper normal limit
b. Aspartate aminotransferase (AST) >2 times upper normal limit
c. Total bilirubin >2 times upper normal limit (except if this is caused by Gilbert disease)
d. Alkaline phosphatase (ALP) >2 times upper normal limit
e. Creatinine >2 times upper normal limit
- Positive human immunodeficiency virus (HIV) serological test at screening and Visit LFinal, not controlled with anti-viral therapy as shown by CD4+ counts = 200/µL (based on central laboratory results)
- Hepatitis B or C infection with the following criteria present at screening:
i. Currently receiving antiviral therapy for this/these infection(s)
and/or
ii. Positive for any of the following (based on central laboratory results):
• Hepatitis B surface antigen (HBsAg), except if in the opinion of the investigator this is due to a previous Hepatitis B vaccination rather than active Hepatitis B infection
• Hepatitis B virus deoxyribonucleic acid (HBV DNA)
• Hepatitis C virus ribonucleic acid (HCV RNA)
- Known coagulation disorder other than hemophilia B
- Thrombocytopenia, defined as a platelet count below 50 × 10^9/L, at screening and Visit L-Final (based on central laboratory results)
- Known severe infection or any other significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, cardiovascular, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease, alcoholism, drug dependency or any other psychological disorder evaluated by the investigator to interfere with adherence to the protocol procedures or with the degree of tolerance to the IMP
- Known significant medical condition that may significantly impact the intended transduction of the vector and/or expression and activity of the protein, including but not limited to:
• Disseminated intravascular coagulation
• Accelerated fibrinolysis
• Advanced liver fibrosis (suggestive of or equal to METAVIR Stage 3 disease; e.g. a FibroScan™ score of =9 kPa is considered equivalent)
- Known history of an allergic reaction or anaphylaxis to factor IX products
- Known uncontrolled allergic conditions or allergy/hypersensitivity to any component of the IMP excipients
- Known history of allergy to corticosteroids
- Known medical condition that would require chronic administration of steroids
- Previous gene therapy treatment
- Receipt of an experimental agent within 60 days prior to screening
- Current participation or anticipated participation within one year after IMP administration in this trial in any other interventional clinical trial involving drugs or devices.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method