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Hemophilia BPhase 1/2NCT02396342

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

A Phase 1/2 study testing AAV5-hFIX in people with Hemophilia B, run by CSL Behring at 7 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Hemophilia B
What is being tested?
AAV5-hFIX
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
7 sitesin 3 countries
Study dates
10 Jun 2015to 15 Apr 2021
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male
  • Age ≥ 18 years
  • 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
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  • 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
  • More than 150 previous exposure days of treatment with FIX protein.
  • 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)
  • 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.

Who cannot join

  • History of FIX inhibitors measured to be ≥ 0.6 Bethesda Units (BU)/mL
  • FIX inhibitors ≥ 0.6 BU/mL at Visit 1 (measured by the local laboratory)
  • Neutralizing antibodies against AAV5 at Visit 1 (measured by the central laboratory)
  • Visit 1 laboratory values (measured by the central laboratory):
  • alanine aminotransferase > 2 times upper normal limit
  • aspartate aminotransferase > 2 times upper normal limit
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  • total bilirubin > 2 times upper normal limit
  • alkaline phosphatase > 2 times upper normal limit
  • creatinine > 1.5 times upper normal limit
  • 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)
  • 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).
  • History of Hepatitis B or C exposure, currently controlled by antiviral therapy
  • Any coagulation disorder other than hemophilia B
  • Thrombocytopenia, defined as a platelet count below 50 × 10E9 / L, at Visit 1 (measured by the central laboratory)
  • Body mass index < 16 or ≥ 35 kg/m2
  • Planned surgery for the initial 6 months after IMP administration in this trial
  • Previous arterial or venous thrombotic event (e.g. acute myocardial infarction, cerebrovascular disease and venous thrombosis)
  • 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
  • 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
  • Known history of an allergic reaction or anaphylaxis to FIX products
  • Known uncontrolled allergic conditions or allergy/hypersensitivity to any component of the IMP excipients
  • Previous gene therapy treatment and/or previous participation in a gene therapy clinical trial
  • Receipt of an experimental agent within 60 days prior to Visit 1
  • Current participation or anticipated participation within one year after IMP administration in this trial in any other interventional clinical trial involving drugs or devices.

Trial locations and contacts

7 sites in 3 countries.

7 sites in 3 countries

Netherlands4 sites

  • uniQure Investigative Site

    Amsterdam

  • uniQure Investigative Site

    Groningen

  • uniQure Investigative Site

    Rotterdam

  • uniQure Investigative Site

    Utrecht

Other trials in Netherlands

Germany2 sites

  • uniQure Investigative Site

    Berlin

  • uniQure Investigative Site

    Frankfurt

Other trials in Germany

Denmark1 site

  • uniQure Investigative Site

    Copenhagen

Other trials in Denmark

About this study

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

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.

Conditions
Hemophilia B
Being tested
AAV5-hFIX
Keywords
Hemophilia B, gene therapy
Medical subject headings
Hemophilia B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AAV5-hFIXGenetic

    Also called AAV5 containing a codon-optimized human factor IX gene

    AAV5hFIX gene therapy

Study groups in NCT02396342
Study groupRoleWhat they receive
Cohort 1ExperimentalAAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion
Receives: Genetic: AAV5-hFIX
Cohort 2ExperimentalAAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion
Receives: Genetic: AAV5-hFIX

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Adverse Events

    Measured: From AMT-060 infusion through end of study (5 years post-dose)

Secondary outcomes (11)

  1. FIX-replacement-therapy-free FIX Activity

    FIX activity measured any time from 72 hours after latest FIX replacement therapy administration and until next administration of FIX replacement therapy. Only assessments performed more than 10 days after most recent FIX-replacement therapy administration included.

    Measured: From AMT-060 infusion through end of study (5 years post-dose)

  2. Total Annualized Bleeding Rate (ABR)

    Annualized: Sum of post-treatment bleeding episodes divided by subjects' average number of years (365.25 days) from treatment start to until the data cutoff date.

    Measured: From AMT-060 infusion through end of study (5 years post-dose)

  3. Total Consumption of FIX Replacement Therapy

    Measured: From AMT-060 infusion through end of study (5 years post dose).

  4. Change From Baseline in Short Form-36 (SF-36) Quality of Life (QoL) Scores

    Scores range from 0 to 100, with a higher score defining a more favorable health state.

    Measured: From AMT-060 infusion through the end of study (5 years post dose)

  5. Time to Vector DNA Stopped Shedding From Blood, Nasal Secretions, Saliva, Urine, Feces, and Semen

    Measured: From AMT-060 infusion through end of study (5 years post dose).

  6. Number of Subjects Developing Neutralizing Antibodies to AAV5

    Measured: From AMT-060 infusion through end of study (5 years post dose)

  7. Total IgG and IgM Antibody Titers to AAV5

    For subjects with a titer of 109350 and 50, the actual titer is >109350 and <50.

    Measured: AMT-060 infusion through end of study (5 years post dose)

  8. Number of Subjects With a Positive AAV5 Capsid-specific T Cell Response

    Specific AAV5 response (results >17 SFC/million PBMCs) were regarded as positive.

    Measured: From AMT-060 infusion through 26 weeks post-dose

  9. Number of Subjects With Antibodies to FIX

    Measured: From AMT-060 infusion through the end of study (5 years post dose)

  10. Number of Subjects With FIX Inhibitors

    Measured: From AMT-060 infusion through the end of study (5 years post dose)

  11. Number of Subjects With Clinically Significant Inflammatory Markers: IL-1β, IL-2, IL-6, INFγ, MCP-1

    Measured: From AMT-060 infusion through 18 weeks post dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Mar 2015 (estimated)
  2. Study start10 Jun 2015
  3. Primary completion15 Apr 2021
  4. Study completion15 Apr 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02396342
Sponsor's protocol ID
CT-AMT-060-01
Status last verified
Jun 2022
First submitted
4 Mar 2015
Last updated
27 Jun 2022
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Miesbach W, Meijer K, Coppens M, Kampmann P, Klamroth R, Schutgens R, Tangelder M, Castaman G, Schwable J, Bonig H, Seifried E, Cattaneo F, Meyer C, Leebeek FWG. Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B. Blood. 2018 Mar 1;131(9):1022-1031. doi: 10.1182/blood-2017-09-804419. Epub 2017 Dec 15.

    PubMed 29246900

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AAV5-hFIX in people with Hemophilia B, run by CSL Behring at 7 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Netherlands, Germany, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (time frame: From AMT-060 infusion through end of study (5 years post-dose)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02396342, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2022.

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