Clinical trial NCT03307980: Long-term Safety and Efficacy Study and Dose-Escalation Substudy of PF 06838435 in Individuals With Hemophilia B
Official title: A FACTOR IX (FIX) GENE TRANSFER, MULTI CENTER EVALUATION OF THE LONG TERM SAFETY AND EFFICACY STUDY OF PF 06838435 AND A DOSE ESCALATION SUBSTUDY IN INDIVIDUALS WITH HEMOPHILIA B
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Hemophilia B
Keywords: gene therapy
BeneGene LTE
hemophilia
SPK-9001
Factor IX
FIX
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2017-10-12
Enrollment: 21
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Incidence of PF-06838435 related adverse events
timeFrame: Baseline up to Year 6
Secondary outcomes:
measure: Incidence of clinically significant changes from baseline
timeFrame: Baseline up to 52 weeks
measure: Incidence of protocol-defined medically important events
timeFrame: Baseline up to 52 weeks
measure: Immune response against AAV capsid protein and hFIX transgene
timeFrame: Baseline up to 52 weeks
measure: Coagulation Clotting Assay for FIX activity levels
timeFrame: Baseline up to Year 6
measure: Mean and standard deviation of vector-derived FIX Activity levels
timeFrame: Baseline up to 52 weeks
measure: Mean and standard deviation of FIX Antigen levels
timeFrame: Baseline up to 52 weeks
measure: Annualized bleeding rate (ABR)
timeFrame: Baseline up to Year 6
measure: Annualized (factor FIX) infusion rate
timeFrame: Baseline up to Year 6
measure: Total factor consumption (IU)
timeFrame: Baseline up to Year 6
measure: Total number of bleeding events
timeFrame: Baseline up to Year 6
measure: Haem-A-QoL
timeFrame: Baseline up to Year 6
measure: EQ-5D-5L
timeFrame: Baseline up to Year 6
measure: Brief Pain Inventory
timeFrame: Year 2 up to Year 6
measure: McGill Pain Questionnaire
timeFrame: Baseline up to 52 weeks
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: UC Davis Ellison Ambulatory Care Clinic
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center department of Radiology
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Midtown Cancer Center
state: California
city: Sacramento
country: United States
facility: UC DavisHealth Main Hospital
state: California
city: Metairie
country: United States
facility: LA Center for Bleeding and Clotting Disorders - Metairie
state: Louisiana
city: Metairie
country: United States
facility: Tulane Lakeside Hospital
state: Louisiana
city: New Orleans
country: United States
facility: LA Center for Bleeding and Clotting Disorders
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University Clinical Translational Unit
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University Hospitals and Clinic
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: New Orleans
country: United States
facility: University Medical Center New Orleans
state: Louisiana
city: Slidell
country: United States
facility: Louisiana Center for Advanced Medicine
state: Louisiana
city: Madison
country: United States
facility: Mississippi Center for Advanced Medicine
state: Mississippi
city: New York
country: United States
facility: Weill Cornell Medicine - New York Presbyterian Hospital
state: New York
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Hamilton
country: Canada
facility: McMaster University Medical Centre - Hamilton Health Sciences
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center - Research Institute
state: Quebec
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Onkoloji Enstitusu Çocuk Hematoloji Onkoloji Bilim Dali
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi Cocuk Sagligi ve Hastaliklari Anabilim Dali
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: