Hemophilia B
Conditions
Brief summary
Study of FLT180a gene therapy in adults with Hemophilia B. Up to 9 patients will be enrolled to receive a single dose of FLT180a and be followed for 52 weeks. Results will confirm the dose for a future Phase 3 study.
Interventions
GENETICverbrinacogene setparvovec
FLT180a is a gene therapy intended to increase endogenous FIX production in adults with Hemophilia B
Sponsors
Spur Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis of Hemophilia B with known severe or moderately severe FIX deficiency (≤2% normal circulating FIX activity) for which the subject is on continuous, stable and adequate FIX prophylaxis * Have acceptable laboratory values of a) Hemoglobin ≥11g/dL; b) Platelets ≥100,000 cells/µL; c) AST, ALT and alkaline phosphatase (ALP) ≤ upper limit of normal (ULN); d) Serum albumin \> lower limit of normal (LLN); e) Total bilirubin ≤1.5 x ULN (except if caused by Gilbert's disease); f) Serum creatinine ≤2.0mg/dL. * Level of neutralizing anti-AAV-S3 antibodies below the limit of the pre-established clinical cutoff using an in vitro transduction inhibition assay within the 4 weeks prior to FLT180a administration * Has demonstrated ability to accurately, independently and in a timely manner enter bleed diary data during the lead-in study, as judged by the investigator * At least 150 exposure days to FIX concentrates * At least 6 months of satisfactory controlled prospective baseline data for bleeding events and FIX consumption data from the FLT-01 lead-in study (ECLIPSE) Key
Exclusion criteria
* Any history of alcohol or drug dependence * Presence of neutralizing anti human FIX antibodies (inhibitor; determined by the Nijmegen modified Bethesda inhibitor assay) at the time of enrolment or a previous history of FIX inhibitor * Subjects at high risk of thromboembolic events * Evidence of advanced liver fibrosis * Prior treatment with a gene transfer medicinal product * Subjects with active hepatitis B or C * Serological evidence of HIV-1, not controlled with anti-viral therapy and as evidenced by cluster of differentiation 4 (CD4)+ counts ≤200 μL * Cytomegalovirus (CMV) immunoglobulin G positive subjects who are CMV polymerase chain reaction (PCR) positive at screening * Known coagulation disorder other than hemophilia B * High sensitivity (hs) troponin-T ≥14 pg/mL during screening * History of uncontrolled cardiac failure, unstable angina, or myocardial infarction or other acute cardiac conditions requiring clinical management in the past 6 months * Planned surgical procedure within the next 12 months requiring prophylactic FIX treatment * Known active severe infection (including documented coronavirus (COVID)-19 infection), or any other significant concurrent, uncontrolled medical condition
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Events | Dosing through last study visit (average of 48 weeks) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With FIX Activity Levels >=5% and >= 10% | Last study visit (average of 48 weeks) | One-Stage aPTT \& Chromogenic Assay (central lab) |
| Number of Participants With FIX Inhibitor at Any Time Point | Dosing through last study visit (average of 48 weeks) | — |
| Number Patients With Bleeding Episode | Dosing through last study visit (average of 48 weeks) | — |
| Mean Time to Cleared Viral Shedding | Dosing through last study visit (average of 48 weeks) | Time of first \<LLD (lower limit detection) value |
| Number of Participants With Abnormal Serum Alpha-fetoprotein Levels | Dosing through last study visit (either Week 26 or W52) | Central lab |
Countries
United Kingdom, United States
Participant flow
Recruitment details
This was a multicenter study with 6 study sites in USA and UK. A total of 7 participants were screened in the trial, of which, 6 participants were treated.
Pre-assignment details
All participants came from the FLT-01 lead-in study (ECLIPSE), from which there was at least 6 months of data collected in a prospective manner detailing bleeding events and FIX consumption.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 29.0 Years STANDARD_DEVIATION 11.66 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United Kingdom | 3 Participants |
| Region of Enrollment United States | 3 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 6 |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
None listed