Hemophilia BPhase 3BENEGENE-2NCT03861273
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
A Phase 3 study testing PF-06838435/ fidanacogene elaparvovec in people with Hemophilia B, run by Pfizer at 65 sites in 16 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years, men only
- Conditions the study is for
- Hemophilia B
- What is being tested?
- PF-06838435/ fidanacogene elaparvovec
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 65 sitesin 16 countries
- Study dates
- 29 Jul 2019to 25 Feb 2028
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
- Study and sponsor staff involved in the conduct of the study and their families
- Unable to comply with study procedures
- Sensitivity to heparin or heparin induced thrombocytopenia
- Sensitivity to any of the study interventions, or components thereof, or drug or other allergy
Trial locations and contacts
65 sites in 16 countries.
65 sites in 16 countries
United States16 sites
Hemophilia and Thrombosis Center at the University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
Regents of the University of Colorado University of Colorado Denver, Office of Grants and Contracts
Aurora, Colorado, 80045
Indiana Hemophilia & Thrombosis Center, Inc.
Indianapolis, Indiana, 46260
Indiana Hemophilia and Thrombosis Center, Inc
Indianapolis, Indiana, 46260
Innovative Hematology, Inc.
Indianapolis, Indiana, 46260
St. Vincent Hospital & Health Care Center, Inc.
Indianapolis, Indiana, 46260
Madison Radiological Group
Madison, Mississippi, 39110
Mississippi Center for Advanced Medicine
Madison, Mississippi, 39110
Center for Human Phenomic Science
Philadelphia, Pennsylvania, 19104
Investigational Drug Service
Philadelphia, Pennsylvania, 19104
Penn Blood Disorder Center
Philadelphia, Pennsylvania, 19104
The Trustees of the University of Pennsylvania, Office of Clinical Research- Legal
Philadelphia, Pennsylvania, 19104
UCSF IDS Pharmacy
San Francisco, California, 94143
University of California, San Francisco - Clinical Research Center
San Francisco, California, 94143
University of California, San Francisco - Outpatient Hematology Clinic
San Francisco, California, 94143
The Regents of the University of California, San Francisco campus
San Francisco, California, 94158
Taiwan6 sites
Changhua Christian Hospital
Changhua, 500
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 807
Chung Shan Medical University Hospital
Taichung, 40201
Chung Shan Medical University
Taichung, 40201
Taichung Veterans General Hospital
Taichung, 40705
National Taiwan University Hospital
Taipei, 10002
Australia5 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
Royal Brisbane and Women's Hospital
Herston, 4029
The Alfred Hospital
Melbourne, Victoria, 3004
Fiona Stanley Hospital
Murdoch, Western Australia, 6150
Germany5 sites
Vivantes Klinikum Friedrichshain
Berlin, 10249
Vivantes Klinikum im Friedrichshain
Berlin, 10249
Universitätsklinikum Bonn Institut für Klinische Chemie und Klinische Pharmakologie -Phase 1-Einheit
Bonn, 53127
Universitätsklinikum Bonn, Anstalt des öffentlichen Rechts
Bonn, 53127
Universitätsklinikum Bonn
Bonn, 53127
United Kingdom5 sites
Glasgow Royal Infirmary
Glasgow, G4 0SF
Guy's and St. Thomas' NHS Foundation Trust
London, SE1 7EH
Newcastle upon Tyne Hospitals NHS FT
Newcastle upon Tyne, TYNE & WEAR, NE1 4LP
Newcastle upon Tyne Hospitals NHS FT
Newcastle upon Tyne, TYNE & WEAR, NE2 4HH
Newcastle upon Tyne Hospitals NHS Foundation Trust
Newcastle upon Tyne, NE2 4HH
Brazil4 sites
Centro de Hematologia e Hemoterapia - Hemocentro de Campinas - UNICAMP
Campinas, São Paulo, 13083-878
Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti- HEMORIO
Rio de Janeiro, 20211-030
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
São Paulo, São Paulo, 05403-010
Centro Estadual de Hemoterapia e Hematologia Marcos Daniel Santos - Hemoes
Vitória, Espírito Santo, 29047-105
Japan4 sites
Saitama Medical University Hospital
Iruma-gun, Saitama, 350-0495
Nara Medical University Hospital
Kashihara, Nara, 634-8522
Sapporo Tokushukai Hospital
Sapporo, Hokkaido, 004-0041
National Center for Child Health and Development
Setagaya-ku, Tokyo, 157 8535
Turkey (Türkiye)4 sites
Acibadem Adana Hospital
Adana, 01130
Gaziantep University Sahinbey Training and Research Hospital
Gaziantep, 27310
Istanbul University Oncology Institute
Istanbul, 34093
Ege University Medical Faculty Hospital
Izmir, 35040
Canada3 sites
McMaster University Medical Centre - Hamilton Health Sciences
Hamilton, Ontario, L8N 3Z5
Juravinski Hospital - Hamilton Health Sciences
Hamilton, Ontario, L8V 1C3
St. Michael's Hospital
Toronto, Ontario, M5B 1W8
Saudi Arabia3 sites
King Abdulaziz Medical City-Ministry of national guard
Riyadh, Kingdom of Saudi Arabia, 14611
King Faisal Specialist Hospital and Research Centre
Riyadh, 11211
King Abdullah International Medical Research Center
Riyadh, 11481
France2 sites
Hopital Cardiologique Louis Pradel - CRTH
Bron, 69677
Hopital Necker
Paris, 75015
Italy2 sites
Azienda Ospedaliero Universitaria Careggi
Florence, 50134
Azienda Ospedaliera Universitaria Federico II
Naples, 80131
Spain2 sites
Hospital Universitari Vall d´Hebrón
Barcelona, 08035
Hospital Universitario Virgen de la Arrixaca
El Palmar, Murcia, 30120
Sweden2 sites
Skåne University Hospital, Department of Hematology, Oncology and Radiation Physics
Malmö, 205 02
ApoEx AB
Malmö, 211 24
Greece1 site
General Hospital of Athens "LAIKO", 2nd Regional Blood Transfusion Center
Athens, 11527
About this study
Official title: PHASE 3, OPEN-LABEL, SINGLE-ARM STUDY TO EVALUATE EFFICACY AND SAFETY OF FIX GENE TRANSFER WITH PF-06838435 (RAAV-SPARK100-HFIX-R338L) IN ADULT MALE PARTICIPANTS WITH MODERATELY SEVERE TO SEVERE HEMOPHILIA B (FIX:C ≤2%) (BENEGENE-2)
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
- Being tested
- PF-06838435/ fidanacogene elaparvovec
- 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)
- Medical subject headings
- Hemophilia B, Hemophilia A, Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-06838435/ fidanacogene elaparvovecBiological
Gene Therapy
| Study group | Role | What they receive |
|---|---|---|
| PF-06838435/ fidanacogene elaparvovec | Experimental | Not described Receives: Biological: PF-06838435/ fidanacogene elaparvovec |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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). 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.
Measured: 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
AIR = number of exogenous infusions (for any reason) received during given time period *365.25/ (Date of last day - date of first day +1) in that time period. 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.
Measured: 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
The certified central clinical laboratory analyzed the sample by two one-stage assays and a chromogenic assay. The first one-stage assay was performed on BCSXP analyzer with Actin-FSL reagent. The second one-stage assay used the same analyzer but SynthAsil as reagent. Data reported in this Outcome Measure is the geometric mean of all assessments from week 12 to Month 15.
Measured: Week 12 to Month 15
Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65
The certified central clinical laboratory analyzed the sample by two one-stage assays and a chromogenic assay. The first one-stage assay was performed on BCSXP analyzer with Actin-FSL reagent. The second one-stage assay used the same analyzer but SynthAsil as reagent.
Measured: Week 12, Week 24, Week 65
Annualized Factor IX (FIX) Consumption From Week 12 to Month 15
Annualized FIX consumption was reported by International Units per kilogram (IU/kg). 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. Data reported in this Outcome Measure is average of all assessments from Week 12 to Month 15.
Measured: 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)
ABR for Spontaneous Bleeds 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. Surgical procedures were excluded from summary/analyses. Spontaneous Bleeds: Bleeding for no apparent/known reason particularly into the joints, muscles, and soft tissues. 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.
Measured: 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)
ABR for Traumatic Bleeds 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. Surgical procedures were excluded from summary/analyses. Traumatic Bleeds: Bleeding event occurring for an apparent/known reason. 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.
Measured: 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)
ABR for Untreated Bleeds 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. Surgical procedures were excluded from summary/analyses. 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.
Measured: 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)
Number of Target Joint Bleeds From Week 12 to Month 15
Target Joint: Defined as a major joint (e.g., hip, elbow, wrist, shoulder, knee, and ankle) into which repeated bleeds occurred (three or more spontaneous bleeds into a single joint within a consecutive 6-month period). A target joint was considered resolved when there were =<2 bleeds into the joint within a 12-month period. Joint Bleed: A bleeding episode characterized by rapid loss of range of motion as compared with baseline that was associated with any combination of the following: pain or an unusual sensation in the joint, palpable swelling, and warmth of the skin over the joint. 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.
Measured: 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)
Percentage of the Participants Without Bleeds From Week 12 to Month 15
Percentage of participants without bleeds (total bleeds and treated bleeds) were summarized by type from Week 12 to Month 15.
Measured: Week 12 to Month 15
Change From Baseline in Joint Health as Measured by the Hemophilia Joint Health Score (HJHS) Instrument at Month 12
A qualified healthcare professional assessed six joints (left ankle, right ankle, left elbow, right elbow, left knee, right knee) scored from 0 to 20 based on: duration of swelling, muscle atrophy, crepitus, flexion loss, extension loss, instability, joint pain, and strength. Gait was scored (0 to 4) based on walking, stairs, running, hopping on one leg. Total score = sum of scores from all joints + gait score ranged from 0 to 124, with the higher the number equating to more severe joint damage.
Measured: Baseline, Month 12
Change From Baseline in Hemophilia Quality of Life (Haem A QoL) Physical Health Domain at Month 12
The Haem-A-QoL questionnaire contained 46 items with ten domains that assessed health in the following areas: Physical Health; Feelings; View of Self; Sports and Leisure; Work and School; Dealing with Haemophilia; Treatment; Future; Family Planning; and Partnership and Sexuality. The physical health domain was considered as the primary domain in this questionnaire, had a transformed score range from 0 to 100, with lower scores representing higher quality of life. In this Outcome Measure Physical Health domain scores of Haem A QoL are reported.
Measured: Baseline, Month 12
Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Month 12
The HAL was a multiple domain measure of the impact of hemophilia on functional abilities in adults. The 7 domains of this instrument contained 42 items in total, as follows: lying/sitting/kneeling/standing; lower (leg) functioning; upper (arm) functioning; transportation; self-care; household tasks; and sports/leisure. Selected items from five of the domains were used to create three components: upper extremity; basic lower extremity; and complex lower extremity activities. The component score of "complex lower extremity activities" was the most important in this questionnaire, had a transformed score range from 0 to 100, higher values indicated less functional limitations in performing tasks.
Measured: Baseline, Month 12
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Results would be posted at secondary completion date.
Measured: Maximum up to 6 years (Week 312) after PF-06838435 infusion
Number of Participants With Adverse Events of Special Interest
Results would be posted at secondary completion date.
Measured: Maximum up to 6 years (Week 312) after PF-06838435 infusion
Number of Participants With Positive Neutralizing Antibody (nAb) to Adeno-associated Virus Vector (AAV) and Anti-Drug Antibody (ADA)
Results would be posted at secondary completion date.
Measured: Maximum up to 6 years (Week 312) after PF-06838435 infusion
ABR for Total Bleeds (Treated and Untreated) Through the Study
Results would be posted at secondary completion date.
Measured: Maximum up to 6 years (Week 312) after PF-06838435 infusion
ABR for Treated Bleeds Through the Study
Results would be posted at secondary completion date.
Measured: Maximum up to 6 years (Week 312) after PF-06838435 infusion
AIR of Exogenous Factor IX Through the Study
Results would be posted at secondary completion date.
Measured: Maximum up to 6 years (Week 312) after PF-06838435 infusion
FIX: C Level Through the Study
Results would be posted at secondary completion date.
Measured: Maximum up to 6 years (Week 312) after PF-06838435 infusion
Annualized Factor IX Consumption Through the Study
Results would be posted at secondary completion date.
Measured: Maximum up to 6 years (Week 312) after PF-06838435 infusion
ABR for Spontaneous and Traumatic, and Untreated Bleeds Through the Study
Results would be posted at secondary completion date.
Measured: Maximum up to 6 years (Week 312) after PF-06838435 infusion
Change From Baseline in Joint Health as Measured by the HJHS Instrument Through the Study
Results would be posted at secondary completion date.
Measured: Baseline, 6 years
Number of Target Joint Bleeds Through the Study
Results would be posted at secondary completion date.
Measured: Maximum up to 6 years (Week 312) after PF-06838435 infusion
Change From Baseline in Haem A QoL Physical Health Domain Through the Study
Results would be posted at secondary completion date.
Measured: Baseline, Maximum up to 6 years (Week 312) after PF-06838435 infusion
Change From Baseline in HAL Complex Lower Extremity Activities Component Score Through the Study
Results would be posted at secondary completion date.
Measured: Baseline, 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2019
- Study start29 Jul 2019
- Primary completion16 Nov 2022
- Study completion25 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hemophilia BStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03861273
- Sponsor's protocol ID
- C0371002
- Other IDs
- 2022-502844-11-00
- Acronym
- BENEGENE-2
- Status last verified
- Sep 2026
- First submitted
- 1 Mar 2019
- Last updated
- 22 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 40750723Cuker 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.
PubMed 39321362
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PHASE 3, OPEN-LABEL, SINGLE-ARM STUDY TO EVALUATE EFFICACY AND SAFETY OF FIX GENE TRANSFER WITH PF-06838435 (RAAV-SPARK100-HFIX-R338L) IN ADULT MALE PARTICIPANTS WITH MODERATELY SEVERE TO SEVERE HEMOPHILIA B (FIX:C ≤2%) (BENEGENE-2)
- ClinicalTrials.gov ID
- NCT03861273
- Acronym / sponsor ID
- BENEGENE-2 / C0371002
- Conditions
- Hemophilia B
- Keywords
- PF 06838435, Hemophilia, Hemophilia B, Factor IX, FIX, Gene Therapy, Infusion, rAAV Spark100 hFIX Padua
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 51 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 29 Jul 2019 (actual)
- Primary completion
- 16 Nov 2022 (actual)
- Study completion
- 25 Feb 2028 (estimated)
- First posted
- 4 Mar 2019 (actual)
- Results
- Posted 27 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PF-06838435/ fidanacogene elaparvovec | Experimental | Biological: PF-06838435/ fidanacogene elaparvovec |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PF-06838435/ fidanacogene elaparvovecGene Therapy | Biological | PF-06838435/ fidanacogene elaparvovec |
Primary outcome
Annualized Bleeding Rate (ABR) for Total Bleeds (Treated and Untreated) From Week 12 to Month 15
Time frame: 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)
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.
26 secondary outcomes
ABR for Treated Bleeds From Week 12 to Month 15
Time frame: 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
Time frame: 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
Time frame: Week 12 to Month 15
Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65
Time frame: Week 12, Week 24, Week 65
Annualized Factor IX (FIX) Consumption From Week 12 to Month 15
Time frame: 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)
ABR for Spontaneous Bleeds From Week 12 to Month 15
Time frame: 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)
ABR for Traumatic Bleeds From Week 12 to Month 15
Time frame: 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)
ABR for Untreated Bleeds From Week 12 to Month 15
Time frame: 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)
Number of Target Joint Bleeds From Week 12 to Month 15
Time frame: 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)
Percentage of the Participants Without Bleeds From Week 12 to Month 15
Time frame: Week 12 to Month 15
Change From Baseline in Joint Health as Measured by the Hemophilia Joint Health Score (HJHS) Instrument at Month 12
Time frame: Baseline, Month 12
Change From Baseline in Hemophilia Quality of Life (Haem A QoL) Physical Health Domain at Month 12
Time frame: Baseline, Month 12
Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Month 12
Time frame: Baseline, Month 12
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
Number of Participants With Adverse Events of Special Interest
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
Number of Participants With Positive Neutralizing Antibody (nAb) to Adeno-associated Virus Vector (AAV) and Anti-Drug Antibody (ADA)
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
ABR for Total Bleeds (Treated and Untreated) Through the Study
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
ABR for Treated Bleeds Through the Study
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
AIR of Exogenous Factor IX Through the Study
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
FIX: C Level Through the Study
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
Annualized Factor IX Consumption Through the Study
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
ABR for Spontaneous and Traumatic, and Untreated Bleeds Through the Study
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
Change From Baseline in Joint Health as Measured by the HJHS Instrument Through the Study
Time frame: Baseline, 6 years
Number of Target Joint Bleeds Through the Study
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
Change From Baseline in Haem A QoL Physical Health Domain Through the Study
Time frame: Baseline, Maximum up to 6 years (Week 312) after PF-06838435 infusion
Change From Baseline in HAL Complex Lower Extremity Activities Component Score Through the Study
Time frame: Baseline, 6 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40750723Wojciechowski 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.
- Derived from this study: PubMed 39321362Cuker 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.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
65 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PF-06838435/ fidanacogene elaparvovec in people with Hemophilia B, run by Pfizer at 65 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 65 sites in United States, Taiwan, Australia, Germany, United Kingdom and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Annualized Bleeding Rate (ABR) for Total Bleeds (Treated and Untreated) From Week 12 to Month 15 (time frame: 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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03861273, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2026; AzTrials last refreshed its copy on 26 Oct 2026.