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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 (BENEGENE-2)

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ClinicalTrials.gov Identifier: NCT03861273
Recruitment Status : Recruiting
First Posted : March 4, 2019
Last Update Posted : October 10, 2023
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Description
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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).

Condition or disease Intervention/treatment Phase
Hemophilia B Biological: PF-06838435/ fidanacogene elaparvovec Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : July 29, 2019
Actual Primary Completion Date : November 16, 2022
Estimated Study Completion Date : March 27, 2030

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: PF-06838435/ fidanacogene elaparvovec Biological: PF-06838435/ fidanacogene elaparvovec
Gene Therapy


Outcome Measures
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Primary Outcome Measures :
  1. Annualized bleeding rate (ABR) for total bleeds [ Time Frame: Week 12 to Month 15 post PF-06838435 infusion ]

Secondary Outcome Measures :
  1. Annualized bleeding rate (ABR) for treated bleeds [ Time Frame: Week 12 to Month 15 post PF-06838435 infusion ]
  2. Annualized infusion rate (AIR) of exogenous Factor IX [ Time Frame: Week 12 to Month 15 post PF-06838435 infusion ]
  3. Vector derived Factor IX activity (FIX:C) level at steady state [ Time Frame: Week 12 to Month 15 post PF-06838435 infusion ]
  4. Factor IX consumption [ Time Frame: Week 12 to Month 15 post PF-06838435 infusion ]
  5. Annualized number of bleeding events of specific type: spontaneous and traumatic, and untreated [ Time Frame: Week 12 to Month 15 post PF-06838435 infusion ]
  6. Frequency of target joint bleeds [ Time Frame: Week 12 to Month 15 post PF-06838435 infusion ]
  7. Percentage of the participants without bleeds [ Time Frame: Week 12 to Month 15 post PF-06838435 infusion ]
  8. Change in joint health as measured by the Hemophilia Joint Health Score (HJHS) instrument [ Time Frame: 12 months post PF-06838435 infusion ]
  9. Patient Reported Outcome (PRO) instrument - Hemophilia Quality of Life (Haem A QoL) Physical Health domain [ Time Frame: 12 months post PF-06838435 infusion ]
  10. Patient Reported Outcome (PRO) instrument - Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score [ Time Frame: 12 months post PF-06838435 infusion ]
  11. Annualized Bleeding Rate for total bleeds [ Time Frame: From Month 15 to Month 24, by yearly intervals after 24 months, and across 6 years of follow-up ]
  12. Vector-derived FIX:C level by study visit and the geometric mean at each yearly interval [ Time Frame: From Month 15 to Month 24, by yearly intervals after 24 months, and across 6 years of follow-up ]
  13. Annualized infusion rate (AIR) of exogenous Factor IX [ Time Frame: From Month 15 to Month 24, by yearly intervals after 24 months, and across 6 years of follow-up ]
  14. ABR for treated bleeds [ Time Frame: From Month 15 to Month 24, by yearly intervals after 24 months, and across 6 years of follow-up ]
  15. Annualized Factor IX consumption [ Time Frame: From Month 15 to Month 24, by yearly intervals after 24 months, and across 6 years of follow-up ]
  16. Annualized number of bleeding events of specific type: spontaneous and traumatic, and untreated [ Time Frame: From Month 15 to Month 24, by yearly intervals after 24 months, and across 6 years of follow-up ]
  17. Hemophilia Joint Health Score (HJHS) [ Time Frame: Annually for 6 years ]
  18. Frequency of target joint bleeds [ Time Frame: From Month 15 to Month 24, by yearly intervals after 24 months, and across 6 years of follow-up ]
  19. Patient Reported Outcome (PRO) instrument - Hemophilia Quality of Life (Haem A QoL) Physical Health domain [ Time Frame: Annually for 6 years ]
  20. Patient Reported Outcome (PRO) instrument - Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score [ Time Frame: Annually for 6 years ]
  21. Incidence and severity of all adverse events collected during the study [ Time Frame: For the duration of 6 years after PF-06838435 infusion ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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
  • 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03861273


Contacts
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
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Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
More Information
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Additional Information:

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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03861273    
Other Study ID Numbers: C0371002
2018-003086-33 ( EudraCT Number )
2022-502844-11-00 ( Other Identifier: EU CT )
First Posted: March 4, 2019    Key Record Dates
Last Update Posted: October 10, 2023
Last Verified: October 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Pfizer:
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)
Additional relevant MeSH terms:
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Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
 Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked