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

N/AActive Not RecruitingNCT05568459

Regeneron Pharmaceuticals11 enrolled

Overview

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

Study Type

OBSERVATIONAL

Enrollment

Conditions

Hemophilia B

Interventions

Eligibility

Sex: MALEMin age: 16 Years

Medical Language ↔ Plain English

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

Locations (17)

University of Colorado Hemophilia and Thrombosis Center

Aurora, Colorado, United States

Yale HTC

New Haven, Connecticut, United States

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

University of Florida

Gainesville, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, United States

University of Michigan

Ann Arbor, Michigan, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

University of Texas Health Science Center at Houston

Houston, Texas, United States

McMaster University Medical Centre - Hamilton Health Sciences

Hamilton, Ontario, Canada

...and 7 more locations

Outcomes

Primary Outcomes

Annualized bleeding rate (ABR)

Time frame: At least 26 Weeks Up to 96 weeks

Secondary Outcomes

Annualized utilization (IU/kg) of FIX replacement therapy

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Through the end of the study, approximately 96 weeks

Incidence of adverse event (AEs)

Time frame: Through the end of the study, approximately 96 Weeks

Severity of AEs

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to 96 Weeks

Annualized medically attended visit (MAV) rate 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

Time frame: Up to 96 Weeks

Detection of antibodies to adeno-associated virus (AAV) capsid proteins

Time frame: Up to 96 Weeks