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: March 8, 2024
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: May 12, 2023
• First Posted Date: June 22, 2023
• Last Update Posted Date: March 8, 2024
• Actual Study Start Date: June 30, 2023
• Estimated Primary Completion Date: June 6, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 19, 2023)

• 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
• 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
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 19, 2023)

• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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.
• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate Impact of Efanesoctocog Alfa on Long-term Joint Health in Participants With Hemophilia A
• Official Title: Prospective, Observational , Multicenter Study of Effectiveness of Efanesoctocog Alfa on Long-term Joint Health in Patients With Hemophilia A

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.

• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• 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.
• Condition: Hemophilia A

Intervention

Drug: Efanesoctocog Alfa BIVV001

Given per investigator's discretion

Other Name: ALTUVIIIO

Study Groups/Cohorts

• 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

  Intervention: Drug: Efanesoctocog Alfa BIVV001
• Cohort B (On-Demand treatment)
  Participants receiving on-demand treatment with efanesoctocog alfa who fulfil the overall study inclusion/exclusion criteria
  Intervention: Drug: Efanesoctocog Alfa BIVV001

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 19, 2023): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 6, 2028
• Estimated Primary Completion Date: June 6, 2028 (Final data collection date for primary outcome measure)

Eligibility 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."

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05911763
• Other Study ID Numbers: OBS17523; U1111-1281-8840 ( Registry Identifier: ICTRP )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

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

• Current Responsible Party: Sanofi
• Original Responsible Party: Same as current
• Current Study Sponsor: Sanofi
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: March 2024