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Trial of AAV5-hFIX in Severe or Moderately Severe Hemophilia B

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02396342
First Posted: March 24, 2015
Last Update Posted: February 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Chiesi Farmaceutici S.p.A.
Information provided by (Responsible Party):
UniQure Biopharma B.V.
  Purpose
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.

Condition Intervention Phase
Hemophilia B Genetic: AAV5-hFIX Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by UniQure Biopharma B.V.:

Primary Outcome Measures:
  • Adverse Events [ Time Frame: Five years ]

Secondary Outcome Measures:
  • FIX-replacement-therapy-free FIX activity [ Time Frame: Five years ]
  • Bleeding rate [ Time Frame: Five years ]
  • Total consumption of FIX replacement therapy [ Time Frame: Five years ]
  • Short Form-36 Quality of Life scores [ Time Frame: Five years ]
  • Vector DNA in semen, blood, saliva, nasal secretions, urine and faeces [ Time Frame: Up to five years but maximally until the date that 3 consecutive samples are negative ]
  • Neutralizing antibodies to AAV5 [ Time Frame: Five years ]
  • Total (IgM and IgG) antibodies to AAV5 [ Time Frame: Five years ]
  • AAV5 capsid-specific T cells [ Time Frame: 26 weeks ]
  • Antibodies to FIX [ Time Frame: Five years ]
  • FIX inhibitors [ Time Frame: Five years ]
  • Inflammatory markers: Interleukin(IL)-1β, IL-2, IL-6, Interferon γ, Monocyte Chemotactic Protein-1 [ Time Frame: 18 weeks ]

Estimated Enrollment: 10
Study Start Date: May 2015
Estimated Study Completion Date: May 2021
Estimated Primary Completion Date: May 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion
Genetic: AAV5-hFIX
AAV5hFIX gene therapy
Other Name: AAV5 containing a codon-optimized human factor IX gene
Experimental: Cohort 2
AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion
Genetic: AAV5-hFIX
AAV5hFIX gene therapy
Other Name: AAV5 containing a codon-optimized human factor IX gene

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02396342


Locations
Denmark
uniQure Investigative Site
Copenhagen, Denmark
Germany
uniQure Investigative Site
Berlin, Germany
uniQure Investigative Site
Frankfurt, Germany
Netherlands
uniQure Investigative Site
Amsterdam, Netherlands
uniQure Investigative Site
Groningen, Netherlands
uniQure Investigative Site
Rotterdam, Netherlands
uniQure Investigative Site
Utrecht, Netherlands
Sponsors and Collaborators
UniQure Biopharma B.V.
Chiesi Farmaceutici S.p.A.
Investigators
Study Director: uniQure Clinical Trials UniQure Biopharma B.V.
  More Information

Responsible Party: UniQure Biopharma B.V.
ClinicalTrials.gov Identifier: NCT02396342     History of Changes
Other Study ID Numbers: CT-AMT-060-01
First Submitted: March 4, 2015
First Posted: March 24, 2015
Last Update Posted: February 3, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by UniQure Biopharma B.V.:
Hemophilia B, gene therapy

Additional relevant MeSH terms:
Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked


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