A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B

NCT03861273 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: C03710022022-502844-11-00
• Study Type: interventional
• Target: 51
• Locations: 16 countries
• Sites: 65

Brief Summary

This study will evaluate the efficacy and safety of PF-06838435 (a gene therapy drug) in adult male participants with moderately severe to severe hemophilia B (participants that have a Factor IX circulating activity of 2% or less). The gene therapy is designed to introduce genetic material into cells to compensate for missing or non-functioning Factor IX. Eligible study participants will have completed a minimum 6 months of routine Factor IX prophylaxis therapy during the lead in study (C0371004). Participants will be dosed once (intravenously) and will be evaluated over the course of 6 years. The main objective of the study will evaluate the annualized bleeding rate \[ABR\] for participants treated with gene therapy versus standard of care (SOC) therapy (FIX prophylaxis replacement regimen).

Conditions

Hemophilia B

Keywords

PF 06838435; Hemophilia; Hemophilia B; Factor IX; FIX; Gene Therapy; Infusion; rAAV Spark100 hFIX Padua; rAAV Spark100-hFIX-R338L; R338L; BeneGene 2; Hematological Diseases; Annualized bleeding rate (ABR)

Outcome Measures

Primary Outcomes (1)

• Annualized Bleeding Rate (ABR) for Total Bleeds (Treated and Untreated) From Week 12 to Month 15

  ABR = number of total bleeding episodes on study during the given time period) \*365.25/ (Date of last day - date of first day +1) in that time period. Surgical procedures were excluded from summary/analyses. Treated Bleed: An event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding (protocol definition, unless specifically referring to untreated bleed). Untreated Bleed: A bleeding event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. This outcome measure compared data collected from lead-in study C0371004 and from current study C0371002. Pre-infusion period = at least 6 months of prospectively collected data while receiving FIX prophylaxis replacement therapy in lead-in study C0371004 up to dosing in current study C0371002.

  Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm)

Secondary Outcomes (26)

• ABR for Treated Bleeds From Week 12 to Month 15

  Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm)

• Annualized Infusion Rate (AIR) of Exogenous FIX From Week 12 to Month 15

  Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm)

• Steady State Circulating Factor IX (FIX:C) From Week 12 to Month 15

  Week 12 to Month 15

• Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65

  Week 12, Week 24, Week 65

• Annualized Factor IX (FIX) Consumption From Week 12 to Month 15

  Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm)

Study Arms (1)

PF-06838435/ fidanacogene elaparvovec

EXPERIMENTAL

Biological: PF-06838435/ fidanacogene elaparvovec

Interventions

PF-06838435/ fidanacogene elaparvovec BIOLOGICAL

Gene Therapy

PF-06838435/ fidanacogene elaparvovec

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males who completed 6 months of Factor IX prophylaxis therapy during the lead-in study (C0371004) prior to providing consent at the screening visit for this study.
• Documented moderately severe to severe hemophilia B (Factor IX activity \< =2%)
• Previous experience with FIX therapy (=\>50 documented exposure days to a FIX protein product)
• Suspension of prophylaxis therapy for hemophilia B after administration of the study drug
• Laboratory values (hemoglobin, platelets and creatinine) within study specified limits
• Agree to contraception until components of the drug are eliminated from their body
• Capable of giving signed informed consent

You may not qualify if:

• Anti-AAVRh74var neutralizing antibodies (nAb) titer above the established threshold (ie, positive for nAb).
• History of inhibitor to Factor IX or inhibitor detected during screening. Clinical signs or symptoms of decreased response to Factor IX
• Hypersensitivity to Factor IX replacement product or IV immunoglobulin administration
• History of chronic infection or other chronic disease
• Any conditions associated with increased thromboembolic risk
• Concurrent clinically significant major disease or condition unsuitable for participation and/or may interfere with the interpretation of study results
• Laboratory values at screening visit that are abnormal or outside acceptable study limits
• Current unstable liver or biliary disease
• Currently on antiviral therapy for hepatitis B or C
• Planned surgical procedure requiring Factor IX surgical prophylactic factor treatment 15 months from screening visit
• Use of restricted therapies (e.g., blood products, acetylsalicylic acid \[aspirin\] or ibuprofen, other investigational therapy, and by-passing agents)
• Previously dosed in a gene therapy research trial at any time or in an interventional clinical study within 12 weeks of screening visit
• Active hepatitis B or C; hepatitis B surface antigen, hepatitis B virus deoxyribonucleic acid positivity, or hepatitis C virus ribonucleic acid positivity
• Significant liver disease
• Serological evidence of HIV1 or HIV2 infection with either CD4+ cell count \<=200 mm3 and/or a viral load \>20 copies/mL

Sponsors & Collaborators

• Pfizer: lead

Study Sites (65)

UCSF IDS Pharmacy

San Francisco, California, 94143, United States

Location

University of California, San Francisco - Clinical Research Center

San Francisco, California, 94143, United States

Location

University of California, San Francisco - Outpatient Hematology Clinic

San Francisco, California, 94143, United States

Location

The Regents of the University of California, San Francisco campus

San Francisco, California, 94158, United States

Location

Hemophilia and Thrombosis Center at the University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Regents of the University of Colorado University of Colorado Denver, Office of Grants and Contracts

Aurora, Colorado, 80045, United States

Location

Indiana Hemophilia & Thrombosis Center, Inc.

Indianapolis, Indiana, 46260, United States

Location

Indiana Hemophilia and Thrombosis Center, Inc

Indianapolis, Indiana, 46260, United States

Location

Innovative Hematology, Inc.

Indianapolis, Indiana, 46260, United States

Location

St. Vincent Hospital & Health Care Center, Inc.

Indianapolis, Indiana, 46260, United States

Location

Madison Radiological Group

Madison, Mississippi, 39110, United States

Location

Mississippi Center for Advanced Medicine

Madison, Mississippi, 39110, United States

Location

Center for Human Phenomic Science

Philadelphia, Pennsylvania, 19104, United States

Location

Investigational Drug Service

Philadelphia, Pennsylvania, 19104, United States

Location

Penn Blood Disorder Center

Philadelphia, Pennsylvania, 19104, United States

Location

The Trustees of the University of Pennsylvania, Office of Clinical Research- Legal

Philadelphia, Pennsylvania, 19104, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Royal Brisbane and Women's Hospital

Herston, 4029, Australia

Location

Centro Estadual de Hemoterapia e Hematologia Marcos Daniel Santos - Hemoes

Vitória, Espírito Santo, 29047-105, Brazil

Location

Centro de Hematologia e Hemoterapia - Hemocentro de Campinas - UNICAMP

Campinas, São Paulo, 13083-878, Brazil

Location

Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo

São Paulo, São Paulo, 05403-010, Brazil

Location

Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti- HEMORIO

Rio de Janeiro, 20211-030, Brazil

Location

McMaster University Medical Centre - Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

Juravinski Hospital - Hamilton Health Sciences

Hamilton, Ontario, L8V 1C3, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Hopital Cardiologique Louis Pradel - CRTH

Bron, 69677, France

Location

Hopital Necker

Paris, 75015, France

Location

Vivantes Klinikum Friedrichshain

Berlin, 10249, Germany

Location

Vivantes Klinikum im Friedrichshain

Berlin, 10249, Germany

Location

Universitätsklinikum Bonn Institut für Klinische Chemie und Klinische Pharmakologie -Phase 1-Einheit

Bonn, 53127, Germany

Location

Universitätsklinikum Bonn, Anstalt des öffentlichen Rechts

Bonn, 53127, Germany

Location

Universitätsklinikum Bonn

Bonn, 53127, Germany

Location

General Hospital of Athens "LAIKO", 2nd Regional Blood Transfusion Center

Athens, 11527, Greece

Location

Azienda Ospedaliero Universitaria Careggi

Florence, 50134, Italy

Location

Azienda Ospedaliera Universitaria Federico II

Naples, 80131, Italy

Location

Sapporo Tokushukai Hospital

Sapporo, Hokkaido, 004-0041, Japan

Location

Nara Medical University Hospital

Kashihara, Nara, 634-8522, Japan

Location

Saitama Medical University Hospital

Iruma-gun, Saitama, 350-0495, Japan

Location

National Center for Child Health and Development

Setagaya-ku, Tokyo, 157 8535, Japan

Location

King Abdulaziz Medical City-Ministry of national guard

Riyadh, Kingdom of Saudi Arabia, 14611, Saudi Arabia

Location

King Faisal Specialist Hospital and Research Centre

Riyadh, 11211, Saudi Arabia

Location

King Abdullah International Medical Research Center

Riyadh, 11481, Saudi Arabia

Location

Kyung Hee University Hospital at Gangdong

Seoul, 05278, South Korea

Location

Hospital Universitario Virgen de la Arrixaca

El Palmar, Murcia, 30120, Spain

Location

Hospital Universitari Vall d´Hebrón

Barcelona, 08035, Spain

Location

Skåne University Hospital, Department of Hematology, Oncology and Radiation Physics

Malmo, 205 02, Sweden

Location

ApoEx AB

Malmo, 211 24, Sweden

Location

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

Chung Shan Medical University Hospital

Taichung, 40201, Taiwan

Location

Chung Shan Medical University

Taichung, 40201, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Acibadem Adana Hospital

Adana, 01130, Turkey (Türkiye)

Location

Gaziantep University Sahinbey Training and Research Hospital

Gaziantep, 27310, Turkey (Türkiye)

Location

Istanbul University Oncology Institute

Istanbul, 34093, Turkey (Türkiye)

Location

Ege University Medical Faculty Hospital

Izmir, 35040, Turkey (Türkiye)

Location

Newcastle upon Tyne Hospitals NHS FT

Newcastle upon Tyne, TYNE & WEAR, NE1 4LP, United Kingdom

Location

Newcastle upon Tyne Hospitals NHS FT

Newcastle upon Tyne, TYNE & WEAR, NE2 4HH, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, G4 0SF, United Kingdom

Location

Guy's and St. Thomas' NHS Foundation Trust

London, SE1 7EH, United Kingdom

Location

Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, NE2 4HH, United Kingdom

Location

Related Publications (2)

• 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

• Cuker A, Kavakli K, Frenzel L, Wang JD, Astermark J, Cerqueira MH, Iorio A, Katsarou-Fasouli O, Klamroth R, Shapiro AD, Hermans C, Ishiguro A, Leavitt AD, Oldenburg JB, Ozelo MC, Teitel J, Biondo F, Fang A, Fuiman J, McKay J, Sun P, Rasko JEJ, Rupon J; BENEGENE-2 Trial Investigators. Gene Therapy with Fidanacogene Elaparvovec in Adults with Hemophilia B. N Engl J Med. 2024 Sep 26;391(12):1108-1118. doi: 10.1056/NEJMoa2302982.

  PMID: 39321362 DERIVED

Related Links

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

MeSH Terms

Conditions

Hemophilia B; Hemophilia A; Hematologic Diseases

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

C0371004 lead-in ongoing study: did not involve any investigational intervention; designed to collect bleed, infusion data while participants were on their prophylaxis FIX therapy for a minimum of 6 months; data served as within participant comparison group for C0371002; participant flow and AEs are missing as the study has not concluded yet (some participants in the C0371004 are ongoing and supporting a different study NCT04370054) and data will be provided at conclusion of the lead-in study.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2019
• First Posted: March 4, 2019
• Study Start: July 29, 2019
• Primary Completion: November 16, 2022
• Study Completion (Estimated): February 25, 2031
• Last Updated: April 20, 2026
• Results First Posted: March 27, 2024

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (5); US (16); GB (5); AU (5); JP (4); ES (2); TW (6); KR (1); GR (1); FR (2); CA (3); BR (4); SA (3); SE (2); IT (2); TU (4)