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Active, Not Recruiting

NCT Number: NCT03861273

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

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).

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

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

Age range

18 year–65 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 3

Primary location

Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

PF-06838435/ fidanacogene elaparvovec

Biological

Gene Therapy

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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)

    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.

  2. 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)

    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.

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

    Time frame: 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.

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

    Time frame: 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.

  5. 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)

    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.

  6. 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 = 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.

  7. 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 = 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.

  8. 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)

    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.

  9. 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)

    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.

  10. Percentage of the Participants Without Bleeds From Week 12 to Month 15

    Time frame: 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.

  11. Change From Baseline in Joint Health as Measured by the Hemophilia Joint Health Score (HJHS) Instrument at Month 12

    Time frame: Baseline, 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.

  12. Change From Baseline in Hemophilia Quality of Life (Haem A QoL) Physical Health Domain at Month 12

    Time frame: Baseline, 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.

  13. Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Month 12

    Time frame: Baseline, 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.

  14. 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

    Results would be posted at secondary completion date.

  15. Number of Participants With Adverse Events of Special Interest

    Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion

    Results would be posted at secondary completion date.

  16. 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

    Results would be posted at secondary completion date.

  17. ABR for Total Bleeds (Treated and Untreated) Through the Study

    Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion

    Results would be posted at secondary completion date.

  18. ABR for Treated Bleeds Through the Study

    Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion

    Results would be posted at secondary completion date.

  19. AIR of Exogenous Factor IX Through the Study

    Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion

    Results would be posted at secondary completion date.

  20. FIX: C Level Through the Study

    Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion

    Results would be posted at secondary completion date.

  21. Annualized Factor IX Consumption Through the Study

    Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion

    Results would be posted at secondary completion date.

  22. ABR for Spontaneous and Traumatic, and Untreated Bleeds Through the Study

    Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion

    Results would be posted at secondary completion date.

  23. Change From Baseline in Joint Health as Measured by the HJHS Instrument Through the Study

    Time frame: Baseline, 6 years

    Results would be posted at secondary completion date.

  24. Number of Target Joint Bleeds Through the Study

    Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion

    Results would be posted at secondary completion date.

  25. 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

    Results would be posted at secondary completion date.

  26. Change From Baseline in HAL Complex Lower Extremity Activities Component Score Through the Study

    Time frame: Baseline, 6 years

    Results would be posted at secondary completion date.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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)

Acronym: BENEGENE-2

Important dates

Study start
2019
Primary completion
2022
Study completion
2031
First posted
Mar 4, 2019
Registry last updated
Jun 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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