Back to resultsLong-term Safety and Efficacy Study and Dose-Escalation Substudy of PF 06838435 in Individuals With Hemophilia B
Primary Purpose
Hemophilia B
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PF-06838435 (formerly SPK-9001)
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia B focused on measuring gene therapy, BeneGene LTE, hemophilia, SPK-9001, Factor IX, FIX
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:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- UC Davis Comprehensive Cancer Center
- UC Davis Ellison Ambulatory Care Clinic
- UC Davis Medical Center department of Radiology
- UC Davis Medical Center
- UC Davis Midtown Cancer Center
- UC DavisHealth Main Hospital
- LA Center for Bleeding and Clotting Disorders - Metairie
- Tulane Lakeside Hospital
- LA Center for Bleeding and Clotting Disorders
- Tulane University Clinical Translational Unit
- Tulane University Hospitals and Clinics
- Tulane University Hospitals and Clinic
- Tulane University School of Medicine
- University Medical Center New Orleans
- Louisiana Center for Advanced Medicine
- Mississippi Center for Advanced Medicine
- Weill Cornell Medicine - New York Presbyterian Hospital
- The Children's Hospital of Philadelphia
- Royal Prince Alfred Hospital
- McMaster University Medical Centre - Hamilton Health Sciences
- McMaster University Medical Centre
- Juravinski Hospital - Hamilton Health Sciences
- St. Michael's Hospital
- St. Michaels Hospital
- McGill University Health Center - Research Institute
- Royal University Hospital
- Istanbul Universitesi Onkoloji Enstitusu Çocuk Hematoloji Onkoloji Bilim Dali
- Ege Universitesi Tip Fakultesi Cocuk Sagligi ve Hastaliklari Anabilim Dali
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PF-06838435 Dose-Escalation
Arm Description
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.
Outcomes
Primary Outcome Measures
Incidence of PF-06838435 related adverse events
Secondary Outcome Measures
Incidence of clinically significant changes from baseline
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
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
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
Coagulation Clotting assays to assess FIX activity levels (percent of normal)
Mean and standard deviation of vector-derived FIX Activity levels
Mean and standard deviation of peak and steady-state FIX Activity
Mean and standard deviation of FIX Antigen levels
Mean and standard deviation of FIX Antigen levels
Annualized bleeding rate (ABR)
ABR (not including those for surgery)
Annualized (factor FIX) infusion rate
AIR (not including those for surgery)
Total factor consumption (IU)
total quantity of factor infused annually (not including those for surgery) as recorded on the infusion log
Total number of bleeding events
spontaneous and traumatic
Haem-A-QoL
Quality-of-life (QoL) assessment
EQ-5D-5L
Quality-of-life (QoL) assessment
Brief Pain Inventory
Quality-of-life (QoL) assessment
McGill Pain Questionnaire
Quality-of-life (QoL) assessment
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03307980
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 22, 2017 (Actual)
Primary Completion Date
May 29, 2029 (Anticipated)
Study Completion Date
May 29, 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia B
Keywords
gene therapy, BeneGene LTE, hemophilia, SPK-9001, Factor IX, FIX
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PF-06838435 Dose-Escalation
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
PF-06838435 (formerly SPK-9001)
Intervention Description
Gene Therapy: A novel, bioengineered adeno-associated viral vector carrying human factor IX variant
Primary Outcome Measure Information:
Title
Incidence of PF-06838435 related adverse events
Time Frame
Baseline up to Year 6
Secondary Outcome Measure Information:
Title
Incidence of clinically significant changes from baseline
Description
Clinically significant changes in physical examination, vital signs, laboratory values. (to be reported as AEs, regardless of causality)
Time Frame
Baseline up to 52 weeks
Title
Incidence of protocol-defined medically important events
Description
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).
Time Frame
Baseline up to 52 weeks
Title
Immune response against AAV capsid protein and hFIX transgene
Description
Positive immune response based on peripheral blood mononuclear cell (PBMC) results by interferon gamma enzyme-linked immunospot assay (ELISPOT).
Time Frame
Baseline up to 52 weeks
Title
Coagulation Clotting Assay for FIX activity levels
Description
Coagulation Clotting assays to assess FIX activity levels (percent of normal)
Time Frame
Baseline up to Year 6
Title
Mean and standard deviation of vector-derived FIX Activity levels
Description
Mean and standard deviation of peak and steady-state FIX Activity
Time Frame
Baseline up to 52 weeks
Title
Mean and standard deviation of FIX Antigen levels
Description
Mean and standard deviation of FIX Antigen levels
Time Frame
Baseline up to 52 weeks
Title
Annualized bleeding rate (ABR)
Description
ABR (not including those for surgery)
Time Frame
Baseline up to Year 6
Title
Annualized (factor FIX) infusion rate
Description
AIR (not including those for surgery)
Time Frame
Baseline up to Year 6
Title
Total factor consumption (IU)
Description
total quantity of factor infused annually (not including those for surgery) as recorded on the infusion log
Time Frame
Baseline up to Year 6
Title
Total number of bleeding events
Description
spontaneous and traumatic
Time Frame
Baseline up to Year 6
Title
Haem-A-QoL
Description
Quality-of-life (QoL) assessment
Time Frame
Baseline up to Year 6
Title
EQ-5D-5L
Description
Quality-of-life (QoL) assessment
Time Frame
Baseline up to Year 6
Title
Brief Pain Inventory
Description
Quality-of-life (QoL) assessment
Time Frame
Year 2 up to Year 6
Title
McGill Pain Questionnaire
Description
Quality-of-life (QoL) assessment
Time Frame
Baseline up to 52 weeks
10. Eligibility
Sex
Male
Gender Based
Yes
Gender Eligibility Description
Genetic males
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
UC Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
UC Davis Ellison Ambulatory Care Clinic
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
UC Davis Medical Center department of Radiology
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
UC Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
UC Davis Midtown Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
UC DavisHealth Main Hospital
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
LA Center for Bleeding and Clotting Disorders - Metairie
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70001
Country
United States
Facility Name
Tulane Lakeside Hospital
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70001
Country
United States
Facility Name
LA Center for Bleeding and Clotting Disorders
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Tulane University Clinical Translational Unit
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Tulane University Hospitals and Clinics
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Tulane University Hospitals and Clinic
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Tulane University School of Medicine
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
University Medical Center New Orleans
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Louisiana Center for Advanced Medicine
City
Slidell
State/Province
Louisiana
ZIP/Postal Code
70461
Country
United States
Facility Name
Mississippi Center for Advanced Medicine
City
Madison
State/Province
Mississippi
ZIP/Postal Code
39110
Country
United States
Facility Name
Weill Cornell Medicine - New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
McMaster University Medical Centre - Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
McMaster University Medical Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8S 4K1
Country
Canada
Facility Name
Juravinski Hospital - Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 1C3
Country
Canada
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Facility Name
St. Michaels Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Facility Name
McGill University Health Center - Research Institute
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
Royal University Hospital
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N 0W8
Country
Canada
Facility Name
Istanbul Universitesi Onkoloji Enstitusu Çocuk Hematoloji Onkoloji Bilim Dali
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
Ege Universitesi Tip Fakultesi Cocuk Sagligi ve Hastaliklari Anabilim Dali
City
Izmir
ZIP/Postal Code
35100
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C0371003
Description
To obtain contact information for a study center near you, click here.
Learn more about this trial
Long-term Safety and Efficacy Study and Dose-Escalation Substudy of PF 06838435 in Individuals With Hemophilia B
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