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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03861273
Ethics application status
Date submitted
1/03/2019
Date registered
4/03/2019
Date last updated
9/07/2020

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-PADUA) IN ADULT MALE PARTICIPANTS WITH MODERATELY SEVERE TO SEVERE HEMOPHILIA B (FIX:C <=2%) (BENEGENE-2)
Secondary ID [1] 0 0
2018-003086-33
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
Other interventions - PF-06838435/ fidanacogene elaparvovec

Experimental: PF-06838435/ fidanacogene elaparvovec -


Other interventions: PF-06838435/ fidanacogene elaparvovec
Gene Therapy

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

Outcomes
Primary outcome [1] 0 0
Annualized bleeding rate (ABR)
Timepoint [1] 0 0
First 12 months post PF 06838435 infusion
Primary outcome [2] 0 0
Vector derived FIX:C level
Timepoint [2] 0 0
Week 12 to 12 months post PF 06838435 infusion
Secondary outcome [1] 0 0
Annualized infusion rate (AIR) of exogenous Factor IX Activity
Timepoint [1] 0 0
First 12 months post study drug infusion
Secondary outcome [2] 0 0
Annualized Factor IX Activity consumption
Timepoint [2] 0 0
12 months post study drug infusion
Secondary outcome [3] 0 0
Annualized number of bleeding events of specific type: spontaneous and traumatic, and untreated
Timepoint [3] 0 0
12 months post study drug infusion
Secondary outcome [4] 0 0
Frequency of target joint bleeds
Timepoint [4] 0 0
12 months post study drug infusion
Secondary outcome [5] 0 0
Percentage of the participants without bleeds
Timepoint [5] 0 0
12 months post study drug infusion
Secondary outcome [6] 0 0
Change in joint health as measured by the Hemophilia Joint Health Score (HJHS) instrument
Timepoint [6] 0 0
12 months post study drug infusion
Secondary outcome [7] 0 0
Patient Reported Outcome (PRO) instrument - Hemophilia Quality of Life (Haem A QoL)
Timepoint [7] 0 0
12 months post study drug infusion
Secondary outcome [8] 0 0
Patient Reported Outcome (PRO) instrument - Hemophilia Activities List (HAL)
Timepoint [8] 0 0
12 months post study drug infusion
Secondary outcome [9] 0 0
Patient Reported Outcome (PRO) instrument - Patient Global Impression of Change-Hemophilia (PGIC-H)
Timepoint [9] 0 0
12 months post study drug infusion
Secondary outcome [10] 0 0
Annualized Bleeding Rate
Timepoint [10] 0 0
Annually for 6 years
Secondary outcome [11] 0 0
Vector derived Factor IX activity (FIX:C) level at steady state
Timepoint [11] 0 0
Annually for 6 years
Secondary outcome [12] 0 0
Annualized infusion rate (AIR) of exogenous Factor IX
Timepoint [12] 0 0
Annually for 6 years
Secondary outcome [13] 0 0
Annualized Factor IX consumption
Timepoint [13] 0 0
Annually for 6 years
Secondary outcome [14] 0 0
Annualized number of bleeding events of specific type: spontaneous and traumatic, and untreated
Timepoint [14] 0 0
Annually for 6 years
Secondary outcome [15] 0 0
Frequency of target joint bleeds
Timepoint [15] 0 0
Annually for 6 years
Secondary outcome [16] 0 0
Patient Reported Outcome (PRO) instrument - Hemophilia Quality of Life (Haem A QoL)
Timepoint [16] 0 0
Annually for 6 years
Secondary outcome [17] 0 0
Patient Reported Outcome (PRO) instrument - Hemophilia Activities List (HAL)
Timepoint [17] 0 0
Annually for 6 years
Secondary outcome [18] 0 0
Patient Reported Outcome (PRO) instrument - Patient Global Impression of Change - Hemophilia (PGIC-H)
Timepoint [18] 0 0
Annually for 6 years
Secondary outcome [19] 0 0
Incidence and severity of all adverse events collected during the study
Timepoint [19] 0 0
For the duration of 6 years after PF-06838435 infusion

Eligibility
Key inclusion criteria
Inclusion Criteria

- Males who completed 6 months of routine Factor IX prophylaxis therapy during the lead
in study (C0371004) and have > = 50 documented exposure days to a FIX protein product
such as recombinant, plasma-derived or extended half-life FIX product

- Moderately severe to severe hemophilia B (Factor IX activity < =2%)

- 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
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

- Anti-AAV Spark100 neutralizing antibodies (nAb) titer, above the established threshold
of 1:1

- 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 intravenous immunoglobulin
administration

- History of chronic infection or other chronic disease

- Any concurrent clinically significant major disease or condition

- Laboratory values at screening visit that are abnormal or outside acceptable study
limits

- Significant and/or unstable liver disease, biliary disease, significant liver fibrosis

- Planned surgical procedure requiring Factor IX surgical prophylactic factor treatment
12 months from screening visit

- Use of restricted therapies (e.g., blood products, acetylsalicylic acid [aspirin] or
ibuprofen, other investigational therapy, and by-passing agents)

- Participation 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 (HBsAg), hepatitis B virus (HBV)
deoxyribonucleic acid (DNA) positivity, or hepatitis C virus (HCV) ribonucleic acid
(RNA) positivity

- Serological evidence of human immunodeficiency virus HIV-1 or HIV-2 with Cluster of
Differentiation 4 positive (CD4+) cell count =200 mm3 and/or viral load >20 copies/mL

- Study and sponsor staff and their families involved in the conduct of the study

- 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
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,SA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
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
RJ
Country [7] 0 0
Brazil
State/province [7] 0 0
SÃO Paulo
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
France
State/province [9] 0 0
Bron
Country [10] 0 0
France
State/province [10] 0 0
Paris
Country [11] 0 0
Greece
State/province [11] 0 0
Athens
Country [12] 0 0
Japan
State/province [12] 0 0
Nara
Country [13] 0 0
Japan
State/province [13] 0 0
Tokyo
Country [14] 0 0
Saudi Arabia
State/province [14] 0 0
Riyadh
Country [15] 0 0
Sweden
State/province [15] 0 0
Malmö
Country [16] 0 0
Taiwan
State/province [16] 0 0
Kaohsiung
Country [17] 0 0
Taiwan
State/province [17] 0 0
Taichung
Country [18] 0 0
Taiwan
State/province [18] 0 0
Taipei
Country [19] 0 0
Turkey
State/province [19] 0 0
Adana
Country [20] 0 0
Turkey
State/province [20] 0 0
Gaziantep
Country [21] 0 0
Turkey
State/province [21] 0 0
Izmir
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Tyne & Wear
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Glasgow

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 objectives of the study are to
compare the annualized bleeding rate [ABR] of the gene therapy to routine prophylaxis from
the lead-in study and to evaluate the impact that it may have on participant's Factor IX
circulating activity [FIX:C].
Trial website
https://clinicaltrials.gov/show/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
Pfizer CT.gov Call Center
Address 0 0
Country 0 0
Phone 0 0
1-800-718-1021
Fax 0 0
Email 0 0
ClinicalTrials.gov_Inquiries@pfizer.com
Contact person for scientific queries

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