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 Details
Study Description
Brief Summary
The primary objective of the study in hemophilia B patients receiving prophylaxis with current FIX replacement therapy is to estimate the annualized bleeding event rates requiring on-demand treatment with FIX replacement therapy for each hemophilia B participant.
The secondary objectives of the study are to:
-
Estimate the annualized utilization (IU/kg) of FIX replacement therapy including prophylaxis and on demand
-
Describe FIX:C in participants on prophylaxis FIX replacement therapy
-
Evaluate the concordance of FIX:C measured by one-stage assay vs. chromogenic substrate assay in participants on prophylaxis FIX replacement therapy
-
Assess FIX replacement therapy associated clinical events and morbidities in hemophilia B participants including thrombo-embolic events, FIX hypersensitivity reactions, and clinical evidence of immunogenicity to FIX replacement therapy
-
Evaluate participant-reported outcomes (PROs) including quality of life using the Haemophilia Quality of Life questionnaire (Haemo-Qol-A), Hemophilia Activity List (HAL) and the EuroQol 5 Dimension 3 Level (EQ-5D-3L)
-
Evaluate joint health by the Hemophilia Joint Health Score (HJHS)
-
Evaluate medically attended visits (MAVs) due to bleeding events related to hemophilia B
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Cohort 1 Male patients with Hemophilia B on current FIX Replacement Therapy prophylaxis |
Other: Non-Interventional
No study treatment will be administered in this study.
|
Outcome Measures
Primary Outcome Measures
- Annualized treated bleeding rate (tABR) [At least 26 Weeks Up to 96 weeks]
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.
Secondary Outcome Measures
- Annualized utilization (IU/kg) of FIX replacement therapy [Up to 96 Weeks]
The annual total dosage of FIX replacement therapy, including prophylaxis and on demand, administered.
- FIX functional (coagulant) activity (FIX:C) in participants on prophylaxis FIX replacement therapy [Through the end of the study, approximately 96 Weeks]
FIX:C includes pre-dose and average activity
- 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 [Up to 96 Weeks]
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.
- Hemophilia Activities List (HAL) total and individual scores [Up to 96 Weeks]
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.
- European Quality of Life 5 Dimensions 3-levels (EQ-5D-3L) score [Up to 96 Weeks]
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.
- Hemophilia Joint Health Score (HJHS) total and individual scores per joint [Up to 96 Weeks]
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.
- Annualized medically attended visit (MAV) rate related to on-demand treated bleeds for any reason [Up to 96 Weeks]
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
Eligibility Criteria
Criteria
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.
-
A positive result during screening of FIX inhibitor.
-
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.
NOTE: Other Inclusion/Exclusion Protocol Defined Criteria Apply.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Trial Management, Regeneron Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- R0000-HEMB-2187