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

NCT03307980 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: C0371003SPK-9001-LTFU-101
• Study Type: interventional
• Target: 21
• Locations: 4 countries
• Sites: 12

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.

Conditions

Hemophilia B

Keywords

gene therapy; BeneGene LTE; hemophilia; SPK-9001; Factor IX; FIX

Outcome Measures

Primary Outcomes (1)

• Incidence of PF-06838435 related adverse events

  Baseline up to Year 6

Secondary Outcomes (14)

• Incidence of clinically significant changes from baseline

  Baseline up to 52 weeks

• Incidence of protocol-defined medically important events

  Baseline up to 52 weeks

• Immune response against AAV capsid protein and hFIX transgene

  Baseline up to 52 weeks

• Coagulation Clotting Assay for FIX activity levels

  Baseline up to Year 6

• Mean and standard deviation of vector-derived FIX Activity levels

  Baseline up to 52 weeks

Study Arms (1)

PF-06838435 Dose-Escalation

EXPERIMENTAL

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)

Interventions

PF-06838435 (formerly SPK-9001) BIOLOGICAL

Gene Therapy: A novel, bioengineered adeno-associated viral vector carrying human factor IX variant

PF-06838435 Dose-Escalation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: Genetic males
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (12)

UC Davis Ellison Ambulatory Care Clinic

Sacramento, California, 95817, United States

Location

UC Davis Medical Center department of Radiology

Sacramento, California, 95817, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

UC DavisHealth Main Hospital

Sacramento, California, 95817, United States

Location

University Medical Center New Orleans

New Orleans, Louisiana, 70112, United States

Location

Mississippi Center for Advanced Medicine

Madison, Mississippi, 39110, United States

Location

Weill Cornell Medicine - New York Presbyterian Hospital

New York, New York, 10065, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

McMaster University Medical Centre - Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

McGill University Health Center - Research Institute

Montreal, Quebec, H4A 3J1, Canada

Location

Ege Universitesi Tip Fakultesi Cocuk Sagligi ve Hastaliklari Anabilim Dali

Izmir, 35100, Turkey (Türkiye)

Location

Related Publications (3)

• Samelson-Jones BJ, Rasko JE, Ducore J, McGuinn C, George LA, von Mackensen S, Borgonuovo G, Agathon D, Smith L, Wilcox LJ, Biondo F, Plonski F. Safety, efficacy and patient-reported outcomes 6 years after fidanacogene elaparvovec in adults with hemophilia B. Blood Adv. 2026 Feb 24:bloodadvances.2025019174. doi: 10.1182/bloodadvances.2025019174. Online ahead of print.

  PMID: 41734390 DERIVED

• Wojciechowski J, Gaitonde P, Hughes JH, Ravva P. Population Modeling of Factor IX Activity Following Administration of Fidanacogene Elaparvovec Gene Therapy in Participants with Hemophilia B. Clin Pharmacokinet. 2025 Oct;64(10):1531-1548. doi: 10.1007/s40262-025-01535-y. Epub 2025 Aug 1.

  PMID: 40750723 DERIVED

• Rasko JEJ, Samelson-Jones BJ, George LA, Giermasz A, Ducore JM, Teitel JM, McGuinn CE, High KA, de Jong YP, Chhabra A, O'Brien A, Smith LM, Winburn I, Rupon J. Fidanacogene Elaparvovec for Hemophilia B - A Multiyear Follow-up Study. N Engl J Med. 2025 Apr 17;392(15):1508-1517. doi: 10.1056/NEJMoa2307159.

  PMID: 40239068 DERIVED

Related Links

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

MeSH Terms

Conditions

Hemophilia B; Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 29, 2017
• First Posted: October 12, 2017
• Study Start: June 22, 2017
• Primary Completion (Estimated): May 29, 2029
• Study Completion (Estimated): October 25, 2029
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

AU (1); CA (2); TU (1); US (8)