Long-term Safety and Efficacy Study and Dose-Escalation Substudy of PF 06838435 in Individuals With Hemophilia B
- Conditions
- Hemophilia B
- Interventions
- Biological: PF-06838435 (formerly SPK-9001)
- Registration Number
- NCT03307980
- Lead Sponsor
- Pfizer
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 21
- Able to provide informed consent and comply with requirements of the study
- Males age 18 to 65 years with confirmed diagnosis of hemophilia B (≤2 IU/dL or ≤2% endogenous factor IX)
- Received ≥50 exposure days to factor IX products
- No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein
- 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
- Evidence of active hepatitis B or C
- Currently on antiviral therapy for hepatitis B or C
- Have significant underlying liver disease
- 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)
- Neutralizing antibody titers to the capsid portion of PF-06838435 above the established threshold
- Sensitivity to heparin or heparin induced thrombocytopenia; sensitivity to any of the study interventions, or components thereof, or drug or other allergy
- Previously dosed in a gene therapy research trial at any time or in an interventional clinical study within 3 months of screening visit
- Any concurrent clinically significant major disease or condition
- Unable or unwilling to comply with the study procedures
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description PF-06838435 Dose-Escalation PF-06838435 (formerly SPK-9001) Single intravaneous infusion of PF-06838435. After 2 participants receive initial dose, data will be evaluated and a decision will be made to escalate or reduce the dose being evaluated, increase the number of participants receiving the dose, or stop dosing. Multiple iterations may be undertaken.
- Primary Outcome Measures
Name Time Method Incidence of PF-06838435 related adverse events Baseline up to Year 6
- Secondary Outcome Measures
Name Time Method Total number of bleeding events Baseline up to Year 6 spontaneous and traumatic
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)
Coagulation Clotting Assay for FIX activity levels Baseline up to Year 6 Coagulation Clotting assays to assess FIX activity levels (percent of normal)
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).
Mean and standard deviation of FIX Antigen levels Baseline up to 52 weeks Mean and standard deviation of FIX Antigen levels
Annualized (factor FIX) infusion rate Baseline up to Year 6 AIR (not including those for surgery)
Brief Pain Inventory Year 2 up to Year 6 Quality-of-life (QoL) assessment
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).
Annualized bleeding rate (ABR) Baseline up to Year 6 ABR (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
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
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
McGill Pain Questionnaire Baseline up to 52 weeks Quality-of-life (QoL) assessment
Trial Locations
- Locations (28)
LA Center for Bleeding and Clotting Disorders - Metairie
🇺🇸Metairie, Louisiana, United States
Tulane Lakeside Hospital
🇺🇸Metairie, Louisiana, United States
University Medical Center New Orleans
🇺🇸New Orleans, Louisiana, United States
Royal University Hospital
🇨🇦Saskatoon, Saskatchewan, Canada
Tulane University School of Medicine
🇺🇸New Orleans, Louisiana, United States
Tulane University Hospitals and Clinic
🇺🇸New Orleans, Louisiana, United States
LA Center for Bleeding and Clotting Disorders
🇺🇸New Orleans, Louisiana, United States
Tulane University Clinical Translational Unit
🇺🇸New Orleans, Louisiana, United States
UC Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
UC Davis Medical Center department of Radiology
🇺🇸Sacramento, California, United States
UC DavisHealth Main Hospital
🇺🇸Sacramento, California, United States
UC Davis Midtown Cancer Center
🇺🇸Sacramento, California, United States
Tulane University Hospitals and Clinics
🇺🇸New Orleans, Louisiana, United States
Louisiana Center for Advanced Medicine
🇺🇸Slidell, Louisiana, United States
Mississippi Center for Advanced Medicine
🇺🇸Madison, Mississippi, United States
Weill Cornell Medicine - New York Presbyterian Hospital
🇺🇸New York, New York, United States
McMaster University Medical Centre
🇨🇦Hamilton, Ontario, Canada
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
St. Michaels Hospital
🇨🇦Toronto, Ontario, Canada
Juravinski Hospital - Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
McMaster University Medical Centre - Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
McGill University Health Center - Research Institute
🇨🇦Montreal, Quebec, Canada
Istanbul Universitesi Onkoloji Enstitusu Çocuk Hematoloji Onkoloji Bilim Dali
🇹🇷Istanbul, Turkey
UC Davis Medical Center
🇺🇸Sacramento, California, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Ege Universitesi Tip Fakultesi Cocuk Sagligi ve Hastaliklari Anabilim Dali
🇹🇷Izmir, Turkey
UC Davis Ellison Ambulatory Care Clinic
🇺🇸Sacramento, California, United States