A Trial That Evaluates Disease Characteristics in Hemophilia B Adult Male Participants Receiving Prophylaxis With Standard of Care Factor IX Protein (FIX) Replacement Therapy

Study Overview
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Brief Summary
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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. After you complete this research study, should you be interested and eligible, you may be offered the opportunity to take part in a future study with this new therapy. 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 you 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 patients Possible complications from the FIX replacement therapy you receive (you will continue to use your usual standard of care FIX prophylaxis for Hemophilia B during the study) How your quality of life is affected by Hemophilia B How your joint health is affected by Hemophilia B How often you visit the emergency room, urgent care center, physician's office, hospital, or have 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

Official Title
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A Prospective Study to Evaluate Disease Characteristics in Hemophilia B Participants Receiving Prophylaxis With Standard of Care FIX Replacement Therapy

Conditions
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Hemophilia B

Intervention / Treatment
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* Other: Non-Interventional


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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 No known hypersensitivity to FIX replacement product. 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: Requires anticoagulant therapy. Lack of adherence with documentation of bleeds and/or prophylaxis replacement therapy administration in the opinion of the investigator. History of FIX inhibitor (clinical or laboratory-based assessment) on 2 or more occasions, as defined in the protocol. Bethesda inhibitor titer greater than the upper limit of normal (ULN) at screening. Pre-existing antibodies to the Adeno-associated virus serotype 8 (AAV8) capsid. Active hepatitis B or C at screening, as defined in protocol. If any of the following pre-existing diagnoses are documented: Cholestatic liver disease Liver cirrhosis Portal hypertension; or Splenomegaly; or Hepatic encephalopathy History of arterial or venous thrombo-embolic events, as defined in the protocol. Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation or other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. Previous receipt of any AAV-gene based therapy or intent to receive AAV-gene based therapy during the study period. NOTE: Other Inclusion/Exclusion Protocol Defined Criteria Apply.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1<br>Male patients with Hemophilia B on current FIX Replacement Therapy prophylaxis | Other: Non-Interventional<br>* No study treatment will be administered in this study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized treated bleeding rate (tABR) | The annual rate of bleeds treated with FIX (Factor IX protein) replacement therapy (on-demand). The total number of bleeds treated with FIX replacement therapy (on-demand) from visit 1 (day 1) to end of study divided over the individual participant's study duration (in days) x 365 days, where treated bleeds data will be collected from a participant -reported e-diary and medically attended visits. | At least 26 Weeks Up to 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized utilization (IU/kg) of FIX replacement therapy | The annual total dosage of FIX replacement therapy, including prophylaxis and on demand, administered. | Up to 96 Weeks | 
| FIX functional (coagulant) activity (FIX:C) in participants on prophylaxis FIX replacement therapy | FIX:C includes pre-dose and average activity | Through the end of the study, approximately 96 Weeks | 
| Difference of FIX:C in participants on prophylaxis FIX replacement therapy by one-stage and chromogenic assays |  | Through the end of the study, approximately 96 weeks | 
| Difference of FIX:C between one-stage assay and chromogenic substrate assay by laboratory in participants on prophylaxis FIX replacement therapy |  | Through the end of the study, approximately 96 weeks | 
| Difference of FIX:C between laboratories by assay (one-stage assay and chromogenic substrate assay) in participants on prophylaxis FIX replacement therapy |  | Through the end of the study, approximately 96 weeks | 
| Incidence of thrombo-embolic events in participants |  | Through the end of the study, approximately 96 Weeks | 
| Severity of thrombo-embolic events in participants |  | Through the end of the study, approximately 96 Weeks | 
| Incidence of FIX hypersensitivity reactions in participants |  | Through the end of the study, approximately 96 Weeks | 
| Severity of FIX hypersensitivity reactions in participants |  | Through the end of the study, approximately 96 Weeks | 
| Incidence of de novo immunogenicity to FIX replacement therapy as reported by the investigator |  | Through the end of the study, approximately 96 Weeks | 
| Hemophilia Quality of Life (Haemo-Qol-A) total and individual domain scores | The Haemo-QoL-A is a self-reported Hemophilia-specific health-related quality of life questionnaire which consists of 41 questions covering 6 domains (Physical Functioning, Role Functioning, Worry, Consequences of Bleeding, Emotional Impact, and Treatment Concerns). Items are answered on a 6-point Likert-type scale, ranging from 0 (None of the time) to 5 (All of the time). Higher scores mean better health-related quality of life or less impairment. | Up to 96 Weeks | 
| Hemophilia Activities List (HAL) total and individual scores | HAL measures of the impact of Hemophilia on functional abilities in adults. The questionnaire consists of 42 items across 7 domains. Each item is rated on a scale of 1 (Impossible) to 6 (Never). Higher scores represent lower levels of activity limitations. | Up to 96 Weeks | 
| European Quality of Life 5 Dimensions 3-levels (EQ-5D-3L) score | EQ-5D-3L health questionnaire is a participant/relative answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. the status of each dimension had 3 possible responses (1 =no problem, 2 some problem 3 =severe problems) in the relevant health dimension. Higher score indicated a worsening health condition. | Up to 96 Weeks | 
| Hemophilia Joint Health Score (HJHS) total and individual scores per joint | The examination involves a physical assessment of elbow, knee, and ankle joints. Individual joints are scored based on duration and presence of swelling, joint pain, flexibility, muscle atrophy, strength, and overall gait. The HJHS is a validated 11-item scoring tool based on radiologic and clinical evaluation, sensitive to detect early signs and minor changes. HJHS ranges from 0 to 124. Higher values in the HJHS represent worse situation for the participant. | Up to 96 Weeks | 
| Annualized medically attended visit (MAV) rate related to on-demand treated bleeds for any reason | The annual rate of MAVs including emergency room (ER) visits, urgent care center visits, physician's office visits, telemedicine visits, or hospitalizations related to bleeds treated on-demand with FIX replacement therapy | Up to 96 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FIX replacement therapy