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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
Date last updated
17/10/2024

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
29/07/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
5/12/2030
Actual
Sample size
Target
Accrual to date
Final
51
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
Belgium
State/province [6] 0 0
Brussels
Country [7] 0 0
Brazil
State/province [7] 0 0
Espirito Santo
Country [8] 0 0
Brazil
State/province [8] 0 0
SP
Country [9] 0 0
Brazil
State/province [9] 0 0
SÃO Paulo
Country [10] 0 0
Brazil
State/province [10] 0 0
Rio de Janeiro
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
France
State/province [12] 0 0
Brest
Country [13] 0 0
France
State/province [13] 0 0
Bron
Country [14] 0 0
France
State/province [14] 0 0
Paris
Country [15] 0 0
Germany
State/province [15] 0 0
Berlin
Country [16] 0 0
Germany
State/province [16] 0 0
Bonn
Country [17] 0 0
Germany
State/province [17] 0 0
Homburg/Saar
Country [18] 0 0
Greece
State/province [18] 0 0
Athens
Country [19] 0 0
Italy
State/province [19] 0 0
Firenze
Country [20] 0 0
Italy
State/province [20] 0 0
Naples
Country [21] 0 0
Japan
State/province [21] 0 0
Hokkaido
Country [22] 0 0
Japan
State/province [22] 0 0
Nara
Country [23] 0 0
Japan
State/province [23] 0 0
Saitama
Country [24] 0 0
Japan
State/province [24] 0 0
Tokyo
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Seoul
Country [26] 0 0
Saudi Arabia
State/province [26] 0 0
Kingdom OF Saudi Arabia
Country [27] 0 0
Saudi Arabia
State/province [27] 0 0
Riyadh
Country [28] 0 0
Spain
State/province [28] 0 0
Murcia
Country [29] 0 0
Spain
State/province [29] 0 0
Barcelona
Country [30] 0 0
Sweden
State/province [30] 0 0
Malmö
Country [31] 0 0
Taiwan
State/province [31] 0 0
Changhua
Country [32] 0 0
Taiwan
State/province [32] 0 0
Kaohsiung
Country [33] 0 0
Taiwan
State/province [33] 0 0
Taichung City
Country [34] 0 0
Taiwan
State/province [34] 0 0
Taichung
Country [35] 0 0
Taiwan
State/province [35] 0 0
Taipei
Country [36] 0 0
Turkey
State/province [36] 0 0
Adana
Country [37] 0 0
Turkey
State/province [37] 0 0
Gaziantep
Country [38] 0 0
Turkey
State/province [38] 0 0
Istanbul
Country [39] 0 0
Turkey
State/province [39] 0 0
Izmir
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Tyne & Wear
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Glasgow
Country [42] 0 0
United Kingdom
State/province [42] 0 0
London
Country [43] 0 0
United Kingdom
State/province [43] 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
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).
Trial website
https://clinicaltrials.gov/study/NCT03861273
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03861273