Long-term Safety and Efficacy Study and Dose-Escalation Substudy of PF 06838435 in Individuals With Hemophilia B

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hemophilia B
• Intervention / Treatment: Biological: PF-06838435 (formerly SPK-9001)

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • McMaster University Medical Centre
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University Medical Centre - Hamilton Health Sciences
    • Hamilton, Ontario, Canada, L8V 1C3
      • Juravinski Hospital - Hamilton Health Sciences
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michaels Hospital
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Center - Research Institute
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Royal University Hospital
• Turkey
  • Istanbul, Turkey, 34093
    • Istanbul Universitesi Onkoloji Enstitusu Çocuk Hematoloji Onkoloji Bilim Dali
  • Izmir, Turkey, 35100
    • Ege Universitesi Tip Fakultesi Cocuk Sagligi ve Hastaliklari Anabilim Dali
• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
    • Sacramento, California, United States, 95817
      • UC Davis Ellison Ambulatory Care Clinic
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center department of Radiology
    • Sacramento, California, United States, 95817
      • UC Davis Midtown Cancer Center
    • Sacramento, California, United States, 95817
      • UC DavisHealth Main Hospital
  • Louisiana
    • Metairie, Louisiana, United States, 70001
      • LA Center for Bleeding and Clotting Disorders - Metairie
    • Metairie, Louisiana, United States, 70001
      • Tulane Lakeside Hospital
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
    • New Orleans, Louisiana, United States, 70112
      • University Medical Center New Orleans
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Clinical Translational Unit
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Hospitals and Clinics
    • New Orleans, Louisiana, United States, 70112
      • LA Center for Bleeding and Clotting Disorders
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Hospitals and Clinic
    • Slidell, Louisiana, United States, 70461
      • Louisiana Center for Advanced Medicine
  • Mississippi
    • Madison, Mississippi, United States, 39110
      • Mississippi Center for Advanced Medicine
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine - New York Presbyterian Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-06838435 Dose-Escalation; 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.	Biological: PF-06838435 (formerly SPK-9001); Gene Therapy: A novel, bioengineered adeno-associated viral vector carrying human factor IX variant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of PF-06838435 related adverse events	Baseline up to Year 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Baseline up to 52 weeks
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).	Baseline up to 52 weeks
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).	Baseline up to 52 weeks
Coagulation Clotting Assay for FIX activity levels	Coagulation Clotting assays to assess FIX activity levels (percent of normal)	Baseline up to Year 6
Mean and standard deviation of vector-derived FIX Activity levels	Mean and standard deviation of peak and steady-state FIX Activity	Baseline up to 52 weeks
Mean and standard deviation of FIX Antigen levels	Mean and standard deviation of FIX Antigen levels	Baseline up to 52 weeks
Annualized bleeding rate (ABR)	ABR (not including those for surgery)	Baseline up to Year 6
Annualized (factor FIX) infusion rate	AIR (not including those for surgery)	Baseline up to Year 6
Total factor consumption (IU)	total quantity of factor infused annually (not including those for surgery) as recorded on the infusion log	Baseline up to Year 6
Total number of bleeding events	spontaneous and traumatic	Baseline up to Year 6
Haem-A-QoL	Quality-of-life (QoL) assessment	Baseline up to Year 6
EQ-5D-5L	Quality-of-life (QoL) assessment	Baseline up to Year 6
Brief Pain Inventory	Quality-of-life (QoL) assessment	Year 2 up to Year 6
McGill Pain Questionnaire	Quality-of-life (QoL) assessment	Baseline up to 52 weeks

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2017
• Primary Completion (Estimated): May 29, 2029
• Study Completion (Estimated): May 29, 2029

Study Registration Dates

• First Submitted: September 29, 2017
• First Submitted That Met QC Criteria: October 6, 2017
• First Posted (Actual): October 12, 2017

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: gene therapy; hemophilia; FIX; Factor IX; BeneGene LTE; SPK-9001
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: C0371003; SPK-9001-LTFU-101 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No