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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03861273




Registration number
NCT03861273
Ethics application status
Date submitted
1/03/2019
Date registered
4/03/2019

Titles & IDs
Public title
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
Scientific 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)
Secondary ID [1] 0 0
2022-502844-11-00
Secondary ID [2] 0 0
C0371002
Universal Trial Number (UTN)
Trial acronym
BENEGENE-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia B 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - PF-06838435/ fidanacogene elaparvovec

Experimental: PF-06838435/ fidanacogene elaparvovec -


Treatment: Other: PF-06838435/ fidanacogene elaparvovec
Gene Therapy

Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualized Bleeding Rate (ABR) for Total Bleeds (Treated and Untreated) From Week 12 to Month 15
Timepoint [1] 0 0
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 outcome [1] 0 0
ABR for Treated Bleeds From Week 12 to Month 15
Timepoint [1] 0 0
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 outcome [2] 0 0
Annualized Infusion Rate (AIR) of Exogenous FIX From Week 12 to Month 15
Timepoint [2] 0 0
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 outcome [3] 0 0
Steady State Circulating Factor IX (FIX:C) From Week 12 to Month 15
Timepoint [3] 0 0
Week 12 to Month 15
Secondary outcome [4] 0 0
Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65
Timepoint [4] 0 0
Week 12, Week 24, Week 65
Secondary outcome [5] 0 0
Annualized Factor IX (FIX) Consumption From Week 12 to Month 15
Timepoint [5] 0 0
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 outcome [6] 0 0
ABR for Spontaneous Bleeds From Week 12 to Month 15
Timepoint [6] 0 0
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 outcome [7] 0 0
ABR for Traumatic Bleeds From Week 12 to Month 15
Timepoint [7] 0 0
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 outcome [8] 0 0
ABR for Untreated Bleeds From Week 12 to Month 15
Timepoint [8] 0 0
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 outcome [9] 0 0
Number of Target Joint Bleeds From Week 12 to Month 15
Timepoint [9] 0 0
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 outcome [10] 0 0
Percentage of the Participants Without Bleeds From Week 12 to Month 15
Timepoint [10] 0 0
Week 12 to Month 15
Secondary outcome [11] 0 0
Change From Baseline in Joint Health as Measured by the Hemophilia Joint Health Score (HJHS) Instrument at Month 12
Timepoint [11] 0 0
Baseline, Month 12
Secondary outcome [12] 0 0
Change From Baseline in Hemophilia Quality of Life (Haem A QoL) Physical Health Domain at Month 12
Timepoint [12] 0 0
Baseline, Month 12
Secondary outcome [13] 0 0
Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Month 12
Timepoint [13] 0 0
Baseline, Month 12
Secondary outcome [14] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Timepoint [14] 0 0
Maximum up to 6 years (Week 312) after PF-06838435 infusion
Secondary outcome [15] 0 0
Number of Participants With Adverse Events of Special Interest
Timepoint [15] 0 0
Maximum up to 6 years (Week 312) after PF-06838435 infusion
Secondary outcome [16] 0 0
Number of Participants With Positive Neutralizing Antibody (nAb) to Adeno-associated Virus Vector (AAV) and Anti-Drug Antibody (ADA)
Timepoint [16] 0 0
Maximum up to 6 years (Week 312) after PF-06838435 infusion
Secondary outcome [17] 0 0
ABR for Total Bleeds (Treated and Untreated) Through the Study
Timepoint [17] 0 0
Maximum up to 6 years (Week 312) after PF-06838435 infusion
Secondary outcome [18] 0 0
ABR for Treated Bleeds Through the Study
Timepoint [18] 0 0
Maximum up to 6 years (Week 312) after PF-06838435 infusion
Secondary outcome [19] 0 0
AIR of Exogenous Factor IX Through the Study
Timepoint [19] 0 0
Maximum up to 6 years (Week 312) after PF-06838435 infusion
Secondary outcome [20] 0 0
FIX: C Level Through the Study
Timepoint [20] 0 0
Maximum up to 6 years (Week 312) after PF-06838435 infusion
Secondary outcome [21] 0 0
Annualized Factor IX Consumption Through the Study
Timepoint [21] 0 0
Maximum up to 6 years (Week 312) after PF-06838435 infusion
Secondary outcome [22] 0 0
ABR for Spontaneous and Traumatic, and Untreated Bleeds Through the Study
Timepoint [22] 0 0
Maximum up to 6 years (Week 312) after PF-06838435 infusion
Secondary outcome [23] 0 0
Change From Baseline in Joint Health as Measured by the HJHS Instrument Through the Study
Timepoint [23] 0 0
Baseline, 6 years
Secondary outcome [24] 0 0
Number of Target Joint Bleeds Through the Study
Timepoint [24] 0 0
Maximum up to 6 years (Week 312) after PF-06838435 infusion
Secondary outcome [25] 0 0
Change From Baseline in Haem A QoL Physical Health Domain Through the Study
Timepoint [25] 0 0
Baseline, Maximum up to 6 years (Week 312) after PF-06838435 infusion
Secondary outcome [26] 0 0
Change From Baseline in HAL Complex Lower Extremity Activities Component Score Through the Study
Timepoint [26] 0 0
Baseline, 6 years

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
65 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [5] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4029 - Brisbane
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Mississippi
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
Brazil
State/province [6] 0 0
Espirito Santo
Country [7] 0 0
Brazil
State/province [7] 0 0
SP
Country [8] 0 0
Brazil
State/province [8] 0 0
SÃO Paulo
Country [9] 0 0
Brazil
State/province [9] 0 0
Rio de Janeiro
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
France
State/province [11] 0 0
Bron
Country [12] 0 0
France
State/province [12] 0 0
Paris
Country [13] 0 0
Germany
State/province [13] 0 0
Berlin
Country [14] 0 0
Germany
State/province [14] 0 0
Bonn
Country [15] 0 0
Germany
State/province [15] 0 0
Homburg/Saar
Country [16] 0 0
Greece
State/province [16] 0 0
Athens
Country [17] 0 0
Japan
State/province [17] 0 0
Hokkaido
Country [18] 0 0
Japan
State/province [18] 0 0
Nara
Country [19] 0 0
Japan
State/province [19] 0 0
Saitama
Country [20] 0 0
Japan
State/province [20] 0 0
Tokyo
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Seoul
Country [22] 0 0
Saudi Arabia
State/province [22] 0 0
Riyadh
Country [23] 0 0
Spain
State/province [23] 0 0
Murcia
Country [24] 0 0
Spain
State/province [24] 0 0
Barcelona
Country [25] 0 0
Sweden
State/province [25] 0 0
Malmö
Country [26] 0 0
Taiwan
State/province [26] 0 0
Changhua
Country [27] 0 0
Taiwan
State/province [27] 0 0
Kaohsiung
Country [28] 0 0
Taiwan
State/province [28] 0 0
Taichung City
Country [29] 0 0
Taiwan
State/province [29] 0 0
Taichung
Country [30] 0 0
Taiwan
State/province [30] 0 0
Taipei
Country [31] 0 0
Turkey
State/province [31] 0 0
Adana
Country [32] 0 0
Turkey
State/province [32] 0 0
Gaziantep
Country [33] 0 0
Turkey
State/province [33] 0 0
Istanbul
Country [34] 0 0
Turkey
State/province [34] 0 0
Izmir
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Tyne & Wear
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Glasgow
Country [37] 0 0
United Kingdom
State/province [37] 0 0
London
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Newcastle upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.