Clinical trial NCT05568459: A Trial That Evaluates Disease Characteristics in Hemophilia B Adult Male Participants Receiving Prophylaxis With Standard of Care Factor IX Protein (FIX) Replacement Therapy
Official title: A Prospective Study to Evaluate Disease Characteristics in Hemophilia B Participants Receiving Prophylaxis With Standard of Care FIX Replacement Therapy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hemophilia B
Keywords: FIX replacement therapy
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-10-05
Enrollment: 120
Sex: MALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male patients with Hemophilia B with a history of FIX:C ≤2% or a documented genotype known to produce severe hemophilia B on current FIX Replacement Therapy prophylaxis

Brief summary: This study is focused on males who have Hemophilia B and who need regular preventive treatment with factor IX protein (FIX) replacement therapy to prevent and also to control their bleeding events. The aim of the study is to gather at least 6 months of information on bleeding events for each individual participant while they continue to use their usual FIX replacement therapy. There is no experimental treatment being tested in this study. The study is informational, and part of a larger program to understand and treat Hemophilia B with a potential experimental new therapy in the future. There is no obligation to agree to taking part in this future study.

The study is looking to answer several other research questions to help understand each participant's individual disease characteristics, including:

* How often to use FIX replacement therapy, both on a regular basis (prophylaxis) and as needed to treat bleeding events
* Measurement of FIX activity (factor IX is a clotting factor) by different laboratories using different types of tests in Hemophilia B participants
* Possible complications from the FIX replacement therapy the patient receives (usual standard of care will continue to be used)
* How quality of life is affected by Hemophilia B
* How joint health is affected by Hemophilia B
* How often the participant visits the emergency room, urgent care center, physician's office, hospital, or has a telemedicine visit as a result of bleeding events
* Whether the body makes antibodies (a protein produced by the body's immune system) against the FIX replacement therapy you receive, which could make the drug less effective or could lead to side effects


Eligibility criteria: Key Inclusion Criteria:

1. Previous experience with FIX therapy (≥50 documented exposure days to a FIX protein product such as recombinant, plasma-derived or extended half-life FIX product) with a current stable prophylaxis regimen for \>2 months prior to enrollment and intention to use FIX replacement therapy for the duration of the study
2. No known hypersensitivity to FIX replacement product
3. Willing to be contacted about a potential future clustered regularly interspaced short palindromic repeats (CRISPR)-based Factor 9 (F9) gene insertion clinical trial in which they may have the opportunity to screen for enrollment

Key Exclusion Criteria:

1. History of any coagulation disorder; requires anticoagulant therapy
2. Lack of adherence with documentation of bleeds and/or prophylaxis replacement therapy administration in the opinion of the investigator, based on medical history
3. History of FIX inhibitor (clinical or laboratory-based assessment) on 2 or more occasions, as defined in the protocol
4. Bethesda inhibitor titer greater than the upper limit of normal (ULN) at screening
5. Any detectable pre-existing antibodies to the Adeno-associated virus serotype 8 (AAV8) capsid; as measured by an assay at prescreening, as defined in the protocol
6. Is positive for hepatitis B or C at screening, as defined in protocol
7. If any of the following pre-existing diagnoses are documented:

   * Cholestatic liver disease
   * Liver cirrhosis
   * Portal hypertension; or
   * Splenomegaly; or
   * Hepatic encephalopathy
8. History of arterial or venous thrombo-embolic events, as defined in the protocol
9. History of clinically significant cardiovascular, respiratory, hepatic, renal (including nephrotic syndrome), gastrointestinal (including protein-losing enteropathy), endocrine, hematological (including thrombophilia), psychiatric, or neurological disease, as assessed by the investigator that may confound the results of the study or poses an additional risk to the participant by study participation
10. Previously received of any AAV-gene based therapy with a marketed gene therapy or in a clinical trial or intent to receive approved or investigational AAV-gene based therapy during the study period

NOTE: Other Inclusion/Exclusion Protocol Defined Criteria Apply

Primary outcomes:
measure: Annualized bleeding rate (ABR)
timeFrame: At least 26 Weeks Up to 96 weeks
Secondary outcomes:
measure: Annualized utilization (IU/kg) of FIX replacement therapy
timeFrame: Up to 96 Weeks
measure: FIX functional (coagulant) activity (FIX:C) in participants on prophylaxis FIX replacement therapy
timeFrame: Through the end of the study, approximately 96 Weeks
measure: Difference of FIX:C in participants on prophylaxis FIX replacement therapy by one-stage and chromogenic assays
timeFrame: Through the end of the study, approximately 96 weeks
measure: Difference of FIX:C between one-stage assay and chromogenic substrate assay by laboratory in participants on prophylaxis FIX replacement therapy
timeFrame: Through the end of the study, approximately 96 weeks
measure: Difference of FIX:C between laboratories by assay (one-stage assay and chromogenic substrate assay) in participants on prophylaxis FIX replacement therapy
timeFrame: Through the end of the study, approximately 96 weeks
measure: Incidence of adverse event (AEs)
timeFrame: Through the end of the study, approximately 96 Weeks
measure: Severity of AEs
timeFrame: Through the end of the study, approximately 96 Weeks
measure: Hemophilia Quality of Life (Haemo-Qol-A) total and individual domain scores
timeFrame: Up to 96 Weeks
measure: Hemophilia Activities List (HAL) total and individual scores
timeFrame: Up to 96 Weeks
measure: European Quality of Life 5 Dimensions 3-levels (EQ-5D-3L) score
timeFrame: Up to 96 Weeks
measure: Hemophilia Joint Health Score (HJHS) total and individual scores per joint
timeFrame: Up to 96 Weeks
measure: Annualized medically attended visit (MAV) rate for any reason
timeFrame: Up to 96 Weeks
measure: Detection of antibodies to adeno-associated virus (AAV) capsid proteins
timeFrame: Up to 96 Weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Orthopaedic Hemophilia Treatment Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hemophilia and Thrombosis Center
state: Colorado
city: New Haven
country: United States
facility: Yale HTC
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Hemophilia and Thrombosis Center
state: Indiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia (CHOP)
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Hamilton
country: Canada
facility: McMaster University Medical Centre - Hamilton Health Sciences
state: Ontario
city: Regensburg
country: Germany
facility: University Hospital of Regensburg
state: Bavaria
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitaet Frankfurt
city: Hamburg
country: Germany
facility: University Hospital Hamburg Eppendorf
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: Hampshire
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary - Clinical Research Facility
state: Scotland
city: London
country: United Kingdom
facility: Barts Health NHS Trust, Royal London Hospital
city: London
country: United Kingdom
facility: St. Thomas' Hospital
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: