A Study to Evaluate Impact of Efanesoctocog Alfa on Long-term Joint Health in Participants With Hemophilia A

Study Overview
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Brief Summary
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This is a prospective, observational, multi-center longitudinal cohort study to describe the real-world effectiveness, safety and treatment usage of efanesoctocog alfa in patients with hemophilia A treated per standard of care in the US and Japan. Patients will be enrolled in the study after the introduction of efanesoctocog alfa in the hemophilia treatment landscape in each study country. Decision to initiate treatment with commercially available efanesoctocog alfa will be made by the treating physician independently from the decision to include patients in the study. No study medication is provided. The data related to efanesoctocog alfa effectiveness, safety and usage will be collected prospectively during routine visits (expected annual/semi-annual visits) for up to 5 years following enrollment /treatment initiation.

Official Title
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Prospective, Observational , Multicenter Study of Effectiveness of Efanesoctocog Alfa on Long-term Joint Health in Patients With Hemophilia A

Conditions
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Hemophilia A

Intervention / Treatment
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* Drug: Efanesoctocog Alfa BIVV001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of hemophilia A Patients starting efanesoctocog alfa treatment as per standard of care no more than one month prior to the enrollment date, for either on demand or prophylaxis. Patients starting efanesoctocog alfa treatment for a surgery event may also be enrolled only if the treatment is prescribed at enrollment. Physician's decision to treat the patient with efanesoctocog alfa is made prior to and independently of participation in the study. Signed and dated informed consent provided by the patient, or by the patient's legally acceptable representative for patients under the legal age before any study-related activities are undertaken. Assent should be obtained for pediatric patients according to local regulations. Exclusion Criteria: Diagnosed with other known bleeding disorder Participation in an investigational medicinal product trial at enrollment visit, or intake of an Investigational Medicinal Product within 3 months prior to inclusion in this study Current diagnosis of a FVIII inhibitor, defined as inhibitor titer ≥0.60 BU/mL The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.
Sexes Eligible for Study
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All

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 A (Prophylactic treatment)<br>All participants on efanesoctocog alfa prophylactic treatment fulfilling the overall study inclusion/exclusion criteria. The prophylactic cohort will include the following sub-cohorts: Sub-cohort A1 (Joint imaging): Participants with severe hemophilia A and joint imaging by Hemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) or Joint Tissue Activity and Damage Exam (JADE) protocol performed within 6 months of initiating treatment with efanesoctocog alfa or within 3 months after initiating treatment with efanesoctocog alfa available. Sub-cohort A2 (Children with no prior joint damage):Participants with severe hemophilia A who have no prior joint damage | Drug: Efanesoctocog Alfa BIVV001<br>* Given per investigator's discretion<br>* Other names: ALTUVIIIO;|
| Cohort B (On-Demand treatment)<br>Participants receiving on-demand treatment with efanesoctocog alfa who fulfil the overall study inclusion/exclusion criteria | Drug: Efanesoctocog Alfa BIVV001<br>* Given per investigator's discretion<br>* Other names: ALTUVIIIO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Annualized joint bleeding rate (AjBR) for treated bleeds | Data will be reported for the effectiveness of efanesoctocog alfa prophylaxis on clinical joint status over 5-years for prophylactic cohort | Up to 5 years | 
| Change from baseline in Annualized joint bleeding rate (AjBR) for all (treated and untreated) bleeds | Data will be reported for the effectiveness of efanesoctocog alfa prophylaxis on clinical joint status over 5-years for prophylactic cohort | Up to 5 years | 
| Number of Target joint development, resolution and/or recurrence | Data will be reported for the effectiveness of efanesoctocog alfa prophylaxis on clinical joint status over 5-years for prophylactic coho | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the Hemophilia Joint Health Score (HJHS v2.1) total/domains scores | HJHS total/domain scores will be reported for prophylactic cohorts (A1 ad A2) | At 1, 2, 3, 4, 5 years | 
| Annual Bleeding Rate (ABR) by type for treated bleeds | Data will be reported for prophylactic cohorts (A1 and A2) | At 1, 2, 3, 4, 5 years | 
| ABR by type all (treated and untreated) bleeds | Data will be reported for prophylactic cohorts (A1 and A2) | At 1, 2, 3, 4, 5 years | 
| ABR by location for treated bleeds | Data will be reported for prophylactic cohorts (A1 and A2) | At 1, 2, 3, 4, 5 years | 
| ABR by location for all (treated and untreated) bleeds | Data will be reported for prophylactic cohorts (A1 and A2) | At 1, 2, 3, 4, 5 years | 
| ABR for all bleeding episodes (including untreated bleeding episodes) | Data will be reported for prophylactic cohorts (A1 and A2) | At 1, 2, 3, 4, 5 years | 
| Percentage of patients with zero joint bleeds | Data will be reported for prophylactic cohorts (A1 and A2) | At 1, 2, 3, 4, 5 years | 
| Annualized factor consumption per participant (IU/kg) assessed by prescription during the follow-up period. | Data will be reported for prophylactic cohorts (A1 and A2) | At 1, 2, 3, 4, 5 years | 
| Annualized injection frequency per participant (assessed by prescription) during the follow- up period | Data will be reported for prophylactic cohorts (A1 and A2) | At 1, 2, 3, 4, 5 years | 
| Treatment adherence (%) as judged by the physician during the follow-up period | Data will be reported for prophylactic cohorts (A1 and A2) | At 1, 2, 3, 4, 5 years | 
| Number of injections of efanesoctocog alfa to treat a bleeding episode. | Data will be reported for prophylactic cohorts (Sub Cohorts A1 and A2) | At 1, 2, 3, 4, 5 years | 
| Total dose of efanesoctocog alfa to treat a bleeding episode. | Data will be reported for prophylactic cohorts (Sub Cohorts A1 and A2) | At 1, 2, 3, 4, 5 years | 
| Number of injections of efanesoctocog alfa to treat a bleeding episode | Data will be reported for On-demand cohort | At 1, 2, 3, 4, 5 years | 
| Total dose of efanesoctocog alfa to treat a bleeding episode | Data will be reported for On-demand cohort | At 1, 2, 3, 4, 5 years | 
| Percentage of bleeding episodes treated with a single injection of efanesoctocog alfa. | Data will be reported for On-demand cohort | At 1, 2, 3, 4, 5 years | 
| Occurrence of a change in treatment regimen (on-demand to prophylactic or prophylactic to on-demand) at baseline and follow-up. | Data will be reported for On-demand cohort | At 1, 2, 3, 4, 5 years | 
| Change from baseline in Hemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) total/domain scores | HEAD-US total/domain scores will be reported for joint imaging sub cohort | At 1, 2, 3, 4 and 5 years | 
| Change from baseline in Hemophilia Early Arthropathy Detection with Joint Tissue Activity and Damage exam (JADE) musculoskeletal ultrasound (MSKUS) (JADE MSKUS) | Data will be reported for consenting participants from the joint imaging sub-cohort | At 1, 2, 3, 4 and 5 years | 
| Change from baseline in synovial hypertrophy by change in mm thickness AND/OR HEAD-US synovitis domain, AND/OR by JADE MSKUS synovial hypertrophy +/- power doppler signal | Data will be reported from the consenting participants from the joint imaging sub-cohort | At 6 months, 1, 2, 3, 4 and 5 years | 
| Occurrence of adverse events (AEs) and serious adverse events (SAEs) | The safety and tolerability of efanesoctocog alfa over 5 years evaluated in all participants | Over 5 year period | 
| Development of inhibitors (neutralizing antibodies directed against factor FVIII as determined via the Nijmegen modified Bethesda assay. | The safety and tolerability of efanesoctocog alfa over 5 years assessed in all participants | Over 5 year period | 
| Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) pain intensity 3a questionnaire (adults) | Effectiveness of efanesoctocog alfa assessed per participants' PROs in all participants | At 3 months, 6 months, 1, 2, 3, 4 and 5 years | 
| Change from baseline in Canadian Hemophilia Outcomes-Kids' Life Assessment Tool (CHO-KLAT) 3.0 (boys ≤18 years old) questionnaire (including Parent Proxy) | Effectiveness of efanesoctocog alfa assessed per participants' PROs in all participants | At 1, 2, 3, 4 and 5 years | 
| Change from baseline in the occurrence of inpatient and outpatient visits, and length of hospital stay related to hemophilia A | Healthcare resource use (HCRU) in efanesoctocog alfa related to hemophilia A over a 5-year period | At 1, 2, 3, 4 and 5 years | 
| Hemostatic response/physician reported during peri-operative period for surgery (major, minor) with efanesoctocog alfa. | Data reported to describe the usage and effectiveness of efanesoctocog alfa during the perioperative period | Over a 5 year period | 
| Number of injections required to maintain hemostasis during perioperative period for surgery (major, minor) | Data reported to describe the usage and effectiveness of efanesoctocog alfa during the perioperative period | Over 5 year period | 
| Dose per injection required to maintain hemostasis during perioperative period for surgery (major, minor) | Data reported to describe the usage and effectiveness of efanesoctocog alfa during the perioperative period | Over 5 year period | 
| Total efanesoctocog alfa consumption (IU) during perioperative period for surgery (major, minor) | Data reported to describe the usage and effectiveness of efanesoctocog alfa during the perioperative period | Over 5 year period | 
| Number of blood component transfusions used during perioperative period for surgery | Data reported to describe the usage and effectiveness of efanesoctocog alfa during the perioperative period | Over 5 year Period | 
| Type of blood component transfusions used during perioperative period for surgery | Data reported to describe the usage and effectiveness of efanesoctocog alfa during the perioperative period | Over 5 year period | 
| Estimated blood loss (ml) (intraoperative and post-operative period) for major surgery | Data reported to describe the usage and effectiveness of efanesoctocog alfa during the perioperative period | Over 5 year period | 
| Number of transfusions required for surgery (intraoperative and post-operative period) | Data reported to describe the usage and effectiveness of efanesoctocog alfa during the perioperative period | Over 5 year period | 
| Duration of hospitalization (major, minor) | Data reported to describe the usage and effectiveness of efanesoctocog alfa during the perioperative period. | Over 5 years period | 
| Dose per injection required to maintain hemostasis during perioperative period for surgery (major, minor) | Data reported to describe the usage and effectiveness of efanesoctocog alfa during the perioperative period for On-demand Cohort | Over a 5 year period |