Brief Title
Trial of AAV5-hFIX in Severe or Moderately Severe Hemophilia B
Official Title
A Phase I/II, Open-label, Uncontrolled, Single-dose, Dose-ascending, Multi-centre Trial Investigating an Adeno-associated Viral Vector Containing a Codon-optimized Human Factor IX Gene (AAV5-hFIX) Administered to Adult Patients With Severe or Moderately Severe Hemophilia B
Brief Summary
This study evaluates how safe gene therapy treatment with AAV5-hFIX is in adult patients with
severe or moderately severe hemophilia B and severe bleeding type.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Adverse Events
Secondary Outcome
FIX-replacement-therapy-free FIX activity
Condition
Hemophilia B
Intervention
AAV5-hFIX
Study Arms / Comparison Groups
Cohort 1
Description: AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Genetic
Estimated Enrollment
10
Start Date
June 10, 2015
Completion Date
May 2021
Primary Completion Date
May 2021
Eligibility Criteria
Inclusion Criteria:
1. Male
2. Age ≥ 18 years
3. Patients with congenital hemophilia B classified as one of the following:
- Known severe FIX deficiency with plasma FIX activity level < 1% and a severe
bleeding phenotype defined by one of the following:
- Currently on prophylactic FIX replacement therapy for a history of bleeding
- Currently on on-demand therapy with a current or past history of frequent
bleeding defined as four or more bleeding episodes in the last 12 months or
chronic hemophilic arthropathy (pain, joint destruction, and loss of range
of motion) in one or more joints
- Known moderately severe FIX deficiency with plasma FIX activity level between ≥
1% and ≤ 2% and a severe bleeding phenotype defined by one of the following:
- Currently on prophylactic FIX replacement therapy for a history of bleeding
- Currently on on-demand therapy with a current or past history of frequent
bleeding defined as four or more bleeding episodes in the last 12 months or
chronic hemophilic arthropathy (pain, joint destruction, and loss of range
of motion) in one or more joints
4. More than 150 previous exposure days of treatment with FIX protein.
5. Acceptance to use a condom during sexual intercourse in the period from
Investigational Medicinal Product (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)
6. Following receipt of verbal and written information about the trial, the subject has
provided signed informed consent before any trial related activity is carried out.
Exclusion Criteria:
1. History of FIX inhibitors measured to be ≥ 0.6 Bethesda Units (BU)/mL
2. FIX inhibitors ≥ 0.6 BU/mL at Visit 1 (measured by the local laboratory)
3. Neutralizing antibodies against AAV5 at Visit 1 (measured by the central laboratory)
4. Visit 1 laboratory values (measured by the central laboratory):
- alanine aminotransferase > 2 times upper normal limit
- aspartate aminotransferase > 2 times upper normal limit
- total bilirubin > 2 times upper normal limit
- alkaline phosphatase > 2 times upper normal limit
- creatinine > 1.5 times upper normal limit
5. Positive HIV serological test at Visit 1, not controlled with anti-viral therapy as
shown by cluster of differentiation 4+ counts ≤ 200 per μL or by a viral load of >200
copies per mL (measured by the central laboratory)
6. Active infection with Hepatitis B or C virus as reflected by Hepatitis B Surface
Antigen (HBsAg), Hepatitis B extracellular Antigen (HBeAg), Hepatitis B Virus
DeoxyriboNucleic Acid (HBV DNA) or Hepatitis C Virus RiboNucleic Acid (HCV RNA)
positivity, respectively, at Visit 1 (measured by the central laboratory).
7. History of Hepatitis B or C exposure, currently controlled by antiviral therapy
8. Any coagulation disorder other than hemophilia B
9. Thrombocytopenia, defined as a platelet count below 50 × 10E9 / L, at Visit 1
(measured by the central laboratory)
10. Body mass index < 16 or ≥ 35 kg/m2
11. Planned surgery for the initial 6 months after IMP administration in this trial
12. Previous arterial or venous thrombotic event (e.g. acute myocardial infarction,
cerebrovascular disease and venous thrombosis)
13. Active severe infection or any other significant concurrent, uncontrolled medical
condition including, but not limited to, renal, hepatic, haematological,
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
14. Known significant medical condition including disseminated intravascular coagulation,
fibrinolysis and liver fibrosis which, in the opinion of the investigator, may
confound, contraindicate or limit the interpretation of either safety or efficacy data
15. Known history of an allergic reaction or anaphylaxis to FIX products
16. Known uncontrolled allergic conditions or allergy/hypersensitivity to any component of
the IMP excipients
17. Previous gene therapy treatment and/or previous participation in a gene therapy
clinical trial
18. Receipt of an experimental agent within 60 days prior to Visit 1
19. Current participation or anticipated participation within one year after IMP
administration in this trial in any other interventional clinical trial involving
drugs or devices.
Gender
Male
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
uniQure Clinical Trials, ,
Location Countries
Denmark
Location Countries
Denmark
Administrative Informations
NCT ID
NCT02396342
Organization ID
CT-AMT-060-01
Responsible Party
Sponsor
Study Sponsor
UniQure Biopharma B.V.
Study Sponsor
uniQure Clinical Trials, Study Director, UniQure Biopharma B.V.
Verification Date
July 2020