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

Phase 3

Active, not recruiting

• Conditions: Hemophilia B
• Interventions: Biological: PF-06838435/ fidanacogene elaparvovec

• Registration Number: NCT03861273
• Lead Sponsor: Pfizer

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-03-01
• Study First Submitted QC: 2019-03-01
• Study First Posted: 2019-03-04
• Study Start: 2019-07-29
• Primary Completion: 2022-11-16
• Results First Submitted: 2023-11-01
• Results First Submitted QC: 2024-02-26
• Results First Posted: 2024-03-27
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-01
• Last Update Posted: 2024-12-03
• Study Completion: 2031-01-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 51

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PF-06838435/ fidanacogene elaparvovec	PF-06838435/ fidanacogene elaparvovec	-

Primary Outcome Measures

Name	Time	Method
Annualized Bleeding Rate (ABR) for Total Bleeds (Treated and Untreated) 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)	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 Outcome Measures

Name	Time	Method
Percentage of the Participants Without Bleeds From Week 12 to Month 15	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.
Change From Baseline in Joint Health as Measured by the Hemophilia Joint Health Score (HJHS) Instrument at Month 12	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.
ABR for Treated Bleeds Through the Study	Maximum up to 6 years (Week 312) after PF-06838435 infusion	Results would be posted at secondary completion date.
Steady State Circulating Factor IX (FIX:C) From Week 12 to Month 15	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.
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)	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.
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)	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.
ABR for Traumatic 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)	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.
Number of Participants With Positive Neutralizing Antibody (nAb) to Adeno-associated Virus Vector (AAV) and Anti-Drug Antibody (ADA)	Maximum up to 6 years (Week 312) after PF-06838435 infusion	Results would be posted at secondary completion date.
Annualized Factor IX Consumption Through the Study	Maximum up to 6 years (Week 312) after PF-06838435 infusion	Results would be posted at secondary completion date.
Change From Baseline in Joint Health as Measured by the HJHS Instrument Through the Study	Baseline, 6 years	Results would be posted at secondary completion date.
Change From Baseline in Haem A QoL Physical Health Domain Through the Study	Baseline, Maximum up to 6 years (Week 312) after PF-06838435 infusion	Results would be posted at secondary completion date.
Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65	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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs	Maximum up to 6 years (Week 312) after PF-06838435 infusion	Results would be posted at secondary completion date.
Number of Participants With Adverse Events of Special Interest	Maximum up to 6 years (Week 312) after PF-06838435 infusion	Results would be posted at secondary completion date.
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)	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.
ABR for Spontaneous 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)	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.
Number of Target Joint 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)	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.
Number of Target Joint Bleeds Through the Study	Maximum up to 6 years (Week 312) after PF-06838435 infusion	Results would be posted at secondary completion date.
ABR for Untreated 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)	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.
Change From Baseline in Hemophilia Quality of Life (Haem A QoL) Physical Health Domain at Month 12	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.
ABR for Spontaneous and Traumatic, and Untreated Bleeds Through the Study	Maximum up to 6 years (Week 312) after PF-06838435 infusion	Results would be posted at secondary completion date.
Change From Baseline in HAL Complex Lower Extremity Activities Component Score Through the Study	Baseline, 6 years	Results would be posted at secondary completion date.
Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Month 12	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.
ABR for Total Bleeds (Treated and Untreated) Through the Study	Maximum up to 6 years (Week 312) after PF-06838435 infusion	Results would be posted at secondary completion date.
AIR of Exogenous Factor IX Through the Study	Maximum up to 6 years (Week 312) after PF-06838435 infusion	Results would be posted at secondary completion date.
FIX: C Level Through the Study	Maximum up to 6 years (Week 312) after PF-06838435 infusion	Results would be posted at secondary completion date.

Trial Locations

Locations (63)

King Abdulaziz Medical City-Ministry of national guard; 🇸🇦 Riyadh, Kingdom OF Saudi Arabia, Saudi Arabia

University of California, San Francisco - Clinical Research Center; 🇺🇸 San Francisco, California, United States

University of California, San Francisco - Outpatient Hematology Clinic; 🇺🇸 San Francisco, California, United States

Hemophilia and Thrombosis Center at the University of Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States

Indiana Hemophilia & Thrombosis Center, Inc.; 🇺🇸 Indianapolis, Indiana, United States

Indiana Hemophilia and Thrombosis Center, Inc; 🇺🇸 Indianapolis, Indiana, United States

St. Vincent Hospital & Health Care Center, Inc.; 🇺🇸 Indianapolis, Indiana, United States

Madison Radiological Group; 🇺🇸 Madison, Mississippi, United States

Mississippi Center for Advanced Medicine; 🇺🇸 Madison, Mississippi, United States

Center for Human Phenomic Science CHPS; 🇺🇸 Philadelphia, Pennsylvania, United States

Center for Human Phenomic Science; 🇺🇸 Philadelphia, Pennsylvania, United States

Investigational Drug Service; 🇺🇸 Philadelphia, Pennsylvania, United States

Penn Blood Disorder Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Royal Prince Alfred Hospital; 🇦🇺 Camperdown, New South Wales, Australia

Royal Brisbane and Women's Hospital; 🇦🇺 Brisbane, Queensland, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

The Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia

Fiona Stanley Hospital; 🇦🇺 Murdoch, Western Australia, Australia

Cliniques Universitaires Saint-Luc; 🇧🇪 Brussels, Belgium

Centro Estadual de Hemoterapia e Hematologia Marcos Daniel Santos - Hemoes; 🇧🇷 Vitoria, Espirito Santo, Brazil

Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo; 🇧🇷 Sao Paulo, SP, Brazil

Centro de Hematologia e Hemoterapia - Hemocentro de Campinas - UNICAMP; 🇧🇷 Campinas, SÃO Paulo, Brazil

Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti - HEMORIO; 🇧🇷 Rio de Janeiro, Brazil

Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti- HEMORIO; 🇧🇷 Rio de Janeiro, Brazil

McMaster University Medical Centre - Hamilton Health Sciences; 🇨🇦 Hamilton, Ontario, Canada

Juravinski Hospital - Hamilton Health Sciences; 🇨🇦 Hamilton, Ontario, Canada

St. Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada

CHRU Brest - Hôpital Morvan; 🇫🇷 Brest, France

Hopital Cardiologique Louis Pradel - CRTH; 🇫🇷 Bron, France

Hopital Necker; 🇫🇷 Paris, France

Vivantes Klinikum Friedrichshain; 🇩🇪 Berlin, Germany

Vivantes Klinikum im Friedrichshain; 🇩🇪 Berlin, Germany

Universitaetsklinikum Bonn; 🇩🇪 Bonn, Germany

Universitätsklinikum Bonn, Anstalt des öffentlichen Rechts; 🇩🇪 Bonn, Germany

Universitätsklinikum Bonn; 🇩🇪 Bonn, Germany

Universität und Universitätsklinikum des Saarlandes; 🇩🇪 Homburg/Saar, Germany

General Hospital of Athens "LAIKO", 2nd Regional Blood Transfusion Center; 🇬🇷 Athens, Greece

Azienda Ospedaliero Universitaria Careggi; 🇮🇹 Firenze, Italy

Azienda Ospedaliera Universitaria Federico II; 🇮🇹 Naples, Italy

Sapporo Tokushukai Hospital; 🇯🇵 Sapporo, Hokkaido, Japan

Nara Medical University Hospital; 🇯🇵 Kashihara, Nara, Japan

Saitama Medical University Hospital; 🇯🇵 Iruma-gun, Saitama, Japan

National Center for Child Health and Development; 🇯🇵 Setagaya-ku, Tokyo, Japan

Kyung Hee University Hospital at Gangdong; 🇰🇷 Seoul, Korea, Republic of

King Faisal Specialist Hospital and Research Centre; 🇸🇦 Riyadh, Saudi Arabia

Hospital Universitario Virgen de la Arrixaca; 🇪🇸 El Palmar, Murcia, Spain

Hospital Universitari Vall d´Hebrón; 🇪🇸 Barcelona, Spain

Skåne University Hospital, Department of Hematology, Oncology and Radiation Physics; 🇸🇪 Malmö, Sweden

ApoEx AB; 🇸🇪 Malmö, Sweden

Changhua Christian Hospital; 🇨🇳 Changhua, Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

Chung Shan Medical University Hospital; 🇨🇳 Taichung City, Taiwan

Chung Shan Medical University; 🇨🇳 Taichung City, Taiwan

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Acibadem Adana Hospital; 🇹🇷 Adana, Turkey

Gaziantep University Sahinbey Training and Research Hospital; 🇹🇷 Gaziantep, Turkey

Istanbul University Oncology Institute; 🇹🇷 Istanbul, Turkey

Ege University Medical Faculty Hospital; 🇹🇷 Izmir, Turkey

Newcastle upon Tyne Hospitals NHS FT; 🇬🇧 Newcastle upon Tyne, Tyne & Wear, United Kingdom

Glasgow Royal Infirmary; 🇬🇧 Glasgow, United Kingdom

Guy's and St. Thomas' NHS Foundation Trust; 🇬🇧 London, United Kingdom

Newcastle upon Tyne Hospitals NHS Foundation Trust; 🇬🇧 Newcastle upon Tyne, United Kingdom