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

• ClinicalTrials.gov Identifier: NCT05911763
• Recruitment Status: Recruiting
• First Posted: June 22, 2023
• Last Update Posted: September 11, 2023
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Hemophilia A	Drug: Efanesoctocog Alfa BIVV001

Study Design

• Study Type: Observational
• Estimated Enrollment: 200 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Prospective, Observational , Multicenter Study of Effectiveness of Efanesoctocog Alfa on Long-term Joint Health in Patients With Hemophilia A
• Actual Study Start Date: June 30, 2023
• Estimated Primary Completion Date: June 6, 2028
• Estimated Study Completion Date: June 6, 2028

Groups and Cohorts

Group/Cohort	Intervention/treatment
Cohort A (Prophylactic treatment); 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; Given per investigator's discretion; Other Name: ALTUVIIIO
Cohort B (On-Demand treatment); Participants receiving on-demand treatment with efanesoctocog alfa who fulfil the overall study inclusion/exclusion criteria	Drug: Efanesoctocog Alfa BIVV001; Given per investigator's discretion; Other Name: ALTUVIIIO

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Approximately 200 patients from sites in the US and Japan will be enrolled in the study after the introduction of efanesoctocog alfa in the hemophilia treatment landscape in each of these two countries. To generate data for the broad real-world population of individuals with hemophilia A, eligible patients will include all ages, sexes and hemophilia A severities, whether on prophylactic or on-demand therapy or if efanesoctocog alfa is taken perioperatively.

Criteria

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."

Contacts and Locations

Contacts

Contact: Trial Transparency email recommended (Toll free number for US & Canada); 1800633-1610 ext Option 6; contact-us@sanofi.com

Locations

United States, California

Center for Inherited Blood Disorders (CIBD)-Site Number:8400001; Recruiting

Orange, California, United States, 92868

United States, Illinois

Bleeding and Clotting Disorders Institute-Site Number:8400005; Recruiting

Peoria, Illinois, United States, 61614-2868

United States, Massachusetts

~Massachusetts General Hospital-Site Number:8400017; Recruiting

Boston, Massachusetts, United States, 02114

United States, Nevada

Alliance for Childhood Diseases-Site Number:8400007; Recruiting

Las Vegas, Nevada, United States, 89135-3011

United States, Texas

University of Texas Southwestern Medical Center-Site Number:8400011; Recruiting

Dallas, Texas, United States, 75390

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT05911763
• Other Study ID Numbers: OBS17523; U1111-1281-8840 ( Registry Identifier: ICTRP )
• First Posted: June 22, 2023
• Last Update Posted: September 11, 2023
• Last Verified: September 2, 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hemophilia A; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn