Clinical trial 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
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
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)
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2019-03-04
Enrollment: 51
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility 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

Primary outcomes:
measure: Annualized Bleeding Rate (ABR) for Total Bleeds (Treated and Untreated) From Week 12 to Month 15
timeFrame: 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:
measure: ABR for Treated Bleeds From Week 12 to Month 15
timeFrame: 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)
measure: Annualized Infusion Rate (AIR) of Exogenous FIX From Week 12 to Month 15
timeFrame: 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)
measure: Steady State Circulating Factor IX (FIX:C) From Week 12 to Month 15
timeFrame: Week 12 to Month 15
measure: Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65
timeFrame: Week 12, Week 24, Week 65
measure: Annualized Factor IX (FIX) Consumption From Week 12 to Month 15
timeFrame: 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)
measure: ABR for Spontaneous Bleeds From Week 12 to Month 15
timeFrame: 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)
measure: ABR for Traumatic Bleeds From Week 12 to Month 15
timeFrame: 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)
measure: ABR for Untreated Bleeds From Week 12 to Month 15
timeFrame: 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)
measure: Number of Target Joint Bleeds From Week 12 to Month 15
timeFrame: 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)
measure: Percentage of the Participants Without Bleeds From Week 12 to Month 15
timeFrame: Week 12 to Month 15
measure: Change From Baseline in Joint Health as Measured by the Hemophilia Joint Health Score (HJHS) Instrument at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Hemophilia Quality of Life (Haem A QoL) Physical Health Domain at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Month 12
timeFrame: Baseline, Month 12
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
measure: Number of Participants With Adverse Events of Special Interest
timeFrame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
measure: Number of Participants With Positive Neutralizing Antibody (nAb) to Adeno-associated Virus Vector (AAV) and Anti-Drug Antibody (ADA)
timeFrame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
measure: ABR for Total Bleeds (Treated and Untreated) Through the Study
timeFrame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
measure: ABR for Treated Bleeds Through the Study
timeFrame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
measure: AIR of Exogenous Factor IX Through the Study
timeFrame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
measure: FIX: C Level Through the Study
timeFrame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
measure: Annualized Factor IX Consumption Through the Study
timeFrame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
measure: ABR for Spontaneous and Traumatic, and Untreated Bleeds Through the Study
timeFrame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
measure: Change From Baseline in Joint Health as Measured by the HJHS Instrument Through the Study
timeFrame: Baseline, 6 years
measure: Number of Target Joint Bleeds Through the Study
timeFrame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
measure: Change From Baseline in Haem A QoL Physical Health Domain Through the Study
timeFrame: Baseline, Maximum up to 6 years (Week 312) after PF-06838435 infusion
measure: Change From Baseline in HAL Complex Lower Extremity Activities Component Score Through the Study
timeFrame: Baseline, 6 years
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco - Clinical Research Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco - Outpatient Hematology Clinic
state: California
city: Aurora
country: United States
facility: Hemophilia and Thrombosis Center at the University of Colorado Anschutz Medical Campus
state: Colorado
city: Indianapolis
country: United States
facility: Indiana Hemophilia & Thrombosis Center, Inc.
state: Indiana
city: Indianapolis
country: United States
facility: Indiana Hemophilia and Thrombosis Center, Inc
state: Indiana
city: Indianapolis
country: United States
facility: St. Vincent Hospital & Health Care Center, Inc.
state: Indiana
city: Madison
country: United States
facility: Madison Radiological Group
state: Mississippi
city: Madison
country: United States
facility: Mississippi Center for Advanced Medicine
state: Mississippi
city: Philadelphia
country: United States
facility: Center for Human Phenomic Science CHPS
state: Pennsylvania
city: Philadelphia
country: United States
facility: Center for Human Phenomic Science
state: Pennsylvania
city: Philadelphia
country: United States
facility: Investigational Drug Service
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Blood Disorder Center
state: Pennsylvania
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
city: Vitoria
country: Brazil
facility: Centro Estadual de Hemoterapia e Hematologia Marcos Daniel Santos - Hemoes
state: Espirito Santo
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
state: SP
city: Campinas
country: Brazil
facility: Centro de Hematologia e Hemoterapia - Hemocentro de Campinas - UNICAMP
state: SÃO Paulo
city: Rio de Janeiro
country: Brazil
facility: Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti- HEMORIO
city: Hamilton
country: Canada
facility: McMaster University Medical Centre - Hamilton Health Sciences
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Hospital - Hamilton Health Sciences
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Bron
country: France
facility: Hopital Cardiologique Louis Pradel - CRTH
city: Paris
country: France
facility: Hopital Necker
city: Berlin
country: Germany
facility: Vivantes Klinikum Friedrichshain
city: Berlin
country: Germany
facility: Vivantes Klinikum im Friedrichshain
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Anstalt des öffentlichen Rechts
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Athens
country: Greece
facility: General Hospital of Athens "LAIKO", 2nd Regional Blood Transfusion Center
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: Naples
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Sapporo
country: Japan
facility: Sapporo Tokushukai Hospital
state: Hokkaido
city: Kashihara
country: Japan
facility: Nara Medical University Hospital
state: Nara
city: Iruma-gun
country: Japan
facility: Saitama Medical University Hospital
state: Saitama
city: Setagaya-ku
country: Japan
facility: National Center for Child Health and Development
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
city: Riyadh
country: Saudi Arabia
facility: King Abdulaziz Medical City-Ministry of national guard
state: Kingdom OF Saudi Arabia
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital and Research Centre
city: El Palmar
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
state: Murcia
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d´Hebrón
city: Malmö
country: Sweden
facility: Skåne University Hospital, Department of Hematology, Oncology and Radiation Physics
city: Malmö
country: Sweden
facility: ApoEx AB
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung City
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung City
country: Taiwan
facility: Chung Shan Medical University
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Adana
country: Turkey
facility: Acibadem Adana Hospital
city: Gaziantep
country: Turkey
facility: Gaziantep University Sahinbey Training and Research Hospital
city: Istanbul
country: Turkey
facility: Istanbul University Oncology Institute
city: Izmir
country: Turkey
facility: Ege University Medical Faculty Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle upon Tyne Hospitals NHS FT
state: Tyne & Wear
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle upon Tyne Hospitals NHS FT
state: Tyne & Wear
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: London
country: United Kingdom
facility: Guy's and St. Thomas' NHS Foundation Trust
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle upon Tyne Hospitals NHS Foundation Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: