Hemophilia B
Conditions
Keywords
gene therapy, BeneGene LTE, hemophilia, SPK-9001, Factor IX, FIX
Brief summary
Long-term safety and efficacy follow-up for participants with Hemophilia B who were previously treated in the C0371005 (formerly SPK-9001-101) study, and a dose-escalation sub-study evaluating safety, tolerability, and kinetics of a higher dose with long-term safety and efficacy follow-up. Participants in the substudy do not need to have participated in C0371005.
Detailed description
Evaluation of the long-term level of persistence and potential late or delayed adverse events associated with PF-06838435 (formerly SPK-9001), assessment of the durability of the transgene expression, and determination of the effects of PF-06838435 on clinical outcomes in individuals who have previously received a single administration of PF-06838435 in the C0371005 study. Amendment 2 of this study incorporates a dose-escalation substudy to evaluate the safety, tolerability, and kinetics of a single IV infusion of PF-06838435 at a higher dose than that used in the C0371005 study. The dose-escalation participants will also be followed for long-term safety and efficacy.
Interventions
BIOLOGICALPF-06838435 (formerly SPK-9001)
Gene Therapy: A novel, bioengineered adeno-associated viral vector carrying human factor IX variant
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study was originally designed as a long-term follow up study for individuals dosed in Study C0371005 to evaluate the overall long-term safety, durability of transgene expression, and effect on clinical outcomes of PF-06838435 mediated gene transfer. For these individuals this study will last for 5 years providing a minimum of 6 years of follow up post vector administration. Amendment 2 of this study introduces a dose-escalation substudy to evaluate the safety, tolerability, and kinetics of a single IV infusion of PF-06838435 at a higher dose(s) than that used in the C0371005 study. For these participants this study will last for a total of 6 years post vector administration.
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
This study is currently only enrolling into the dose-escalation substudy with subsequent long-term follow-up. The Eligibility Criteria for entry into the dose-escalation substudy is presented below: Inclusion Criteria: 1. Able to provide informed consent and comply with requirements of the study 2. Males age 18 to 65 years with confirmed diagnosis of hemophilia B (≤2 IU/dL or ≤2% endogenous factor IX) 3. Received ≥50 exposure days to factor IX products 4. No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein 5. Agree to refrain from donating sperm and either abstain from intercourse or use reliable barrier contraception until 3 consecutive semen samples are negative for vector sequences
Exclusion criteria
1. Evidence of active hepatitis B or C 2. Currently on antiviral therapy for hepatitis B or C 3. Have significant underlying liver disease 4. Serological evidence\* of HIV-1 or HIV-2 with CD4 counts ≤200/mm3 (\* participants who are HIV+ and stable with CD4 count \>200/mm3 and undetectable viral load are eligible to enroll) 5. Neutralizing antibody titers to the capsid portion of PF-06838435 above the established threshold 6. Sensitivity to heparin or heparin induced thrombocytopenia; sensitivity to any of the study interventions, or components thereof, or drug or other allergy 7. Previously dosed in a gene therapy research trial at any time or in an interventional clinical study within 3 months of screening visit 8. Any concurrent clinically significant major disease or condition 9. Unable or unwilling to comply with the study procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of PF-06838435 related adverse events | Baseline up to Year 6 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of clinically significant changes from baseline | Baseline up to 52 weeks | Clinically significant changes in physical examination, vital signs, laboratory values. (to be reported as AEs, regardless of causality) |
| Incidence of protocol-defined medically important events | Baseline up to 52 weeks | Clinical thrombotic events, FIX inhibitor development as assessed by Nijmegen Bethesda assay, Hypersensitivity reaction (eg, bronchospasm and anaphylaxis), Hepatic malignancy, Study intervention-related elevated hepatic transaminases that fail to improve or resolve, Malignancy assessed as having reasonable possibility of being related to study intervention (to be reported as SAEs). |
| Immune response against AAV capsid protein and hFIX transgene | Baseline up to 52 weeks | Positive immune response based on peripheral blood mononuclear cell (PBMC) results by interferon gamma enzyme-linked immunospot assay (ELISPOT). |
| Coagulation Clotting Assay for FIX activity levels | Baseline up to Year 6 | Coagulation Clotting assays to assess FIX activity levels (percent of normal) |
| Mean and standard deviation of vector-derived FIX Activity levels | Baseline up to 52 weeks | Mean and standard deviation of peak and steady-state FIX Activity |
| Mean and standard deviation of FIX Antigen levels | Baseline up to 52 weeks | Mean and standard deviation of FIX Antigen levels |
| Annualized bleeding rate (ABR) | Baseline up to Year 6 | ABR (not including those for surgery) |
| Annualized (factor FIX) infusion rate | Baseline up to Year 6 | AIR (not including those for surgery) |
| Total factor consumption (IU) | Baseline up to Year 6 | total quantity of factor infused annually (not including those for surgery) as recorded on the infusion log |
| Total number of bleeding events | Baseline up to Year 6 | spontaneous and traumatic |
| Haem-A-QoL | Baseline up to Year 6 | Quality-of-life (QoL) assessment |
| EQ-5D-5L | Baseline up to Year 6 | Quality-of-life (QoL) assessment |
| Brief Pain Inventory | Year 2 up to Year 6 | Quality-of-life (QoL) assessment |
| McGill Pain Questionnaire | Baseline up to 52 weeks | Quality-of-life (QoL) assessment |
Countries
Australia, Canada, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed