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

Hemophilia B Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03307980
• Other study ID #: C0371003
• Secondary ID: SPK-9001-LTFU-10
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 22, 2017
• Est. completion date: May 29, 2029

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 21
• Est. completion date: May 29, 2029
• Est. primary completion date: May 29, 2029
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Biological:
• PF-06838435 (formerly SPK-9001)
Gene Therapy: A novel, bioengineered adeno-associated viral vector carrying human factor IX variant

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Canada	Juravinski Hospital - Hamilton Health Sciences	Hamilton	Ontario
Canada	McMaster University Medical Centre	Hamilton	Ontario
Canada	McMaster University Medical Centre - Hamilton Health Sciences	Hamilton	Ontario
Canada	McGill University Health Center - Research Institute	Montreal	Quebec
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	St. Michaels Hospital	Toronto	Ontario
Turkey	Istanbul Universitesi Onkoloji Enstitusu Çocuk Hematoloji Onkoloji Bilim Dali	Istanbul
Turkey	Ege Universitesi Tip Fakultesi Cocuk Sagligi ve Hastaliklari Anabilim Dali	Izmir
United States	Mississippi Center for Advanced Medicine	Madison	Mississippi
United States	LA Center for Bleeding and Clotting Disorders - Metairie	Metairie	Louisiana
United States	Tulane Lakeside Hospital	Metairie	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	Tulane University Hospitals and Clinic	New Orleans	Louisiana
United States	Tulane University Hospitals and Clinics	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Weill Cornell Medicine - New York Presbyterian Hospital	New York	New York
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	UC Davis Ellison Ambulatory Care Clinic	Sacramento	California
United States	UC Davis Medical Center	Sacramento	California
United States	UC Davis Medical Center department of Radiology	Sacramento	California
United States	UC Davis Midtown Cancer Center	Sacramento	California
United States	UC DavisHealth Main Hospital	Sacramento	California
United States	Louisiana Center for Advanced Medicine	Slidell	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of PF-06838435 related adverse events		Baseline up to Year 6
Secondary	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
Secondary	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
Secondary	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
Secondary	Coagulation Clotting Assay for FIX activity levels	Coagulation Clotting assays to assess FIX activity levels (percent of normal)	Baseline up to Year 6
Secondary	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
Secondary	Mean and standard deviation of FIX Antigen levels	Mean and standard deviation of FIX Antigen levels	Baseline up to 52 weeks
Secondary	Annualized bleeding rate (ABR)	ABR (not including those for surgery)	Baseline up to Year 6
Secondary	Annualized (factor FIX) infusion rate	AIR (not including those for surgery)	Baseline up to Year 6
Secondary	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
Secondary	Total number of bleeding events	spontaneous and traumatic	Baseline up to Year 6
Secondary	Haem-A-QoL	Quality-of-life (QoL) assessment	Baseline up to Year 6
Secondary	EQ-5D-5L	Quality-of-life (QoL) assessment	Baseline up to Year 6
Secondary	Brief Pain Inventory	Quality-of-life (QoL) assessment	Year 2 up to Year 6
Secondary	McGill Pain Questionnaire	Quality-of-life (QoL) assessment	Baseline up to 52 weeks

External Links

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