Screening and Lead-in Observational Protocol to Determine Potential Patient Eligibility for Inclusion in AAV Gene Therapy Clinical Trials in Haemophilia B
- Conditions
- bleeding disorderhemophilia10064477
- Registration Number
- NL-OMON54928
- Lead Sponsor
- Freeline Therapeutics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 6
1) Male participants >= 16 years of age.
2) Able to give full informed consent/assent (according to local regulations)
and/or obtain full informed consent from the participant*s legally acceptable
representative (as appropriate) and able to understand and comply with all
requirements of the study, including diary completion.
3) Interested in participation in future gene therapy clinical studies.
4) Subjects with Haemophilia B with known severe or moderately severe FIX
deficiency (<=2% of normal circulating FIX activity) for which the subject is
either on
a) Continuous routine FIX prophylaxis*, OR
b) On demand FIX treatment*
5) If receiving prophylaxis, participant has been on stable** and adequate¶
prophylaxis for at least 2 months prior to enrolment
*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 records3.
* Enrollment of on demand patients is competitive up to a maximum of 10
patients.
** Stable denotes subject has been on prophylaxis with no change in either the
FIX product used, the dose administered or the regimen in the 2 months prior to
enrolment.
¶ Adequate prophylaxis for purposes of this protocol means an annualised
bleeding rate (ABR) of <=8 in the year preceding enrolment.
1) Documented evidence of liver fibrosis and/or liver dysfunction (including,
but not limited to, persistently elevated alanine aminotransaminase, aspartate
aminotransferase, and/or billirubin > 1.5 x upper limit of normal).
2) Prior treatment with a gene transfer medicinal product.
3) Known presence or history of neutralising anti-human FIX antibodies
(inhibitors).
4) Previously established serological evidence of HIV-1.
5) Documented active hepatitis B or C, and HBsAg or HCV RNA viral load
positivity, respectively, or currently on antiviral therapy for hepatitis B or
C. Negative viral assays in 2 samples, collected at least 6 months apart, will
be required to be considered negative.
6) Participants at high risk of thromboembolic events (history of arterial or
venous thromboembolism [e.g. deep vein thrombosis, pulmonary embolism,
non-haemorrhagic stroke, arterial embolus] and those with acquired
thrombophilia. Participants with a history of atrial fibrillation).
7) Known coagulation disorder other than Haemophilia B.
8) Known history of an allergic reaction or anaphylaxis to Factor IX products
or known uncontrolled allergic conditions.
9) Known history of allergy to corticosteroids or to tacrolimus or any other
macrolide.
10) Known medical condition that would require chronic administration of
corticosteroids (excluding topical formulations).
11) History of alcohol or drug dependence.
12) Planned surgical procedure within the next 12 months requiring prophylactic
FIX treatment.
13) Known active severe infection (including documented COVID-19 infection), or
any other significant concurrent, uncontrolled medical condition evaluated by
the investigator to interfere with adherence to the protocol procedures or with
tolerance to gene therapy in a future treatment study including, but not
limited to, renal, hepatic, cardiovascular, ophthalmological, haematological,
immunological, gastrointestinal, endocrine, pulmonary, neurological, cerebral
or psychiatric disease, malignancy or any other psychological disorder.
Study & Design
- Study Type
- Observational invasive
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Data:<br /><br><br /><br>Bleeding episodes based on a prospective data capture period.<br /><br>• Date and time of bleed onset and resolution.<br /><br>• Location of bleed.<br /><br>• Type of bleed (spontaneous, injury).<br /><br>• Severity of bleed.<br /><br>• Concomitant treatments for bleed, if any.<br /><br>• Response to treatment<br /><br><br /><br>Factor IX concentrate consumption based on a prospective data capture period.<br /><br>• FIX concentrate.<br /><br>• Dose.<br /><br>• Dates of administration.<br /><br>• Reason for administration (prevention, bleeding episode).<br /><br>• Frequency of administration.<br /><br>• Total doses.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Data:<br /><br><br /><br>Presence/absence of neutralising antibodies to AAVS3.<br /><br><br /><br>Baseline clinical parameters related to Haemophilia B:<br /><br>• Target joint number measured by Target Joint Assessment at enrolment.<br /><br>• Health Resource Utilisation (usage assessed during Monthly Contact<br /><br>Visits/Calls).<br /><br>• FIX activity levels (obtained as part of patient standard care, if<br /><br>available).</p><br>