Efanesoctocog Alfa Prophylaxis in Patients With Hemophilia A With Synovial Hypertrophy (SYNOVIIIUS)

Prospective Interventional Study of Effectiveness of Efanesoctocog Alfa Prophylaxis on Synovial Hypertrophy in Patients With Hemophilia A

The objective of the study is to assess the improvement of synovial hypertrophy during the 12 months of efanesoctocog alfa prophylaxis once per week (QW) in joints with existing evidence of synovial hypertrophy in participants with hemophilia A.

The study duration for each participant is approximately 12 months.

Study Overview

• Status: Recruiting
• Conditions: Factor VIII Deficiency
• Intervention / Treatment: Drug: Efanesoctocog alfa

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: Contact-US@sanofi.com

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Recruiting
      • Investigational Site Number : 1240003
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Recruiting
      • Investigational Site Number : 1240004
• Japan
  • Hiroshima, Japan, 734-8551
    • Recruiting
    • Investigational Site Number : 3920002
  • Saitama, Japan, 330-8777
    • Recruiting
    • Investigational Site Number : 3920001
  • Tokyo, Japan, 160-0023
    • Recruiting
    • Investigational Site Number : 3920004
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 216-8511
      • Recruiting
      • Investigational Site Number : 3920003
• Taiwan
  • Kaohsiung City, Taiwan, 80756
    • Recruiting
    • Investigational Site Number : 1580003
  • Taichung, Taiwan, 407
    • Recruiting
    • Investigational Site Number : 1580001
  • Taipei, Taiwan, 114
    • Recruiting
    • Investigational Site Number : 1580002
• United States
  • California
    • Los Angeles, California, United States, 90007
      • Recruiting
      • Orthopedic Institute for Children- Site Number : 8400009
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Recruiting
      • Innovative Hematology, Inc.- Site Number : 8400006
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa- Site Number : 8400004
  • Ohio
    • Columbus, Ohio, United States, 43203-1779
      • Recruiting
      • Ohio State University Hospital East- Site Number : 8400001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: Participant is diagnosed with moderate to severe hemophilia A (defined as less than or equal to (≤)5 percent (%) of endogenous FVIII clotting activity) at the time of consent/assent.

Participant is more than or equal to (≥)12 years old at the time of consent/assent.

Participant has existing synovial hypertrophy, defined as at least 1 eligible* joint by the HEAD-US score (Synovitis score: 1 or 2) at the time of consent/assent.

Participant has at least 1 eligible* joint without planned future major orthopedic procedures (example, arthroscopic synovectomy, radioisotopic or chemical synoviorthesis), or major orthopedic procedures in the past 3 months prior to the screening visit (Visit 1).

*An eligible joint is a joint with existing synovial hypertrophy, as defined by a HEAD-US synovitis score of 1 or 2, considering hypertrophic synovium as an indication of the presence of synovitis Participant has received prophylactic treatment with hemophilia prophylaxis prescriptions in the last 12 months prior to the baseline visit (Visit 2).

Participant is capable of understanding the written Informed Consent Form (ICF)/assent form, provides a signed and witnessed written ICF/assent form, and agrees to comply with the protocol requirements.

If male, no contraceptive measures are required for this study.

If female, is not pregnant or breastfeeding, and one of the following conditions applies:

Is a women of nonchildbearing potential (WONCBP) Is a women of childbearing potential (WOCBP) and agrees to use a highly effective contraceptive method, with a failure rate of less than (<)1 percent during the study treatment period (at least until the Week 52/ End of Treatment [EoT] visit).

A WOCBP must have a negative serum pregnancy test at the screening visit (Visit 1) Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply:

Has other associated clotting disorders at the time of consent/assent. Is already under efanesoctocog alfa treatment. Has a current diagnosis of an factor VIII (FVIII) inhibitor, defined as inhibitor titer ≥0.60 BU/mL.

Has ITI within the last 2 years prior to the baseline visit (Visit 2). Has been enrolled in a concurrent clinical interventional study or exposed to other investigational drug(s) within 3 months prior to screening for this study.

Is currently in an institution because of regulatory or legal order (that is, is a prisoner or a patient who is legally institutionalized).

Is not suitable for participation, whatever the reason, as judged by the investigator, including medical or clinical conditions, or patients potentially at risk of noncompliance to study procedures.

Is an employee or family member of the investigator or site personnel. Is involved in a specific situation during study implementation or the course of the study that may raise ethics considerations.

Has hypersensitivity to efanesoctocog alfa or its components or any of its excipients that, in the opinion of the investigator, contraindicates participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Efanesoctocog Alfa; Participants will receive Efanesoctocog Alfa at 50 international unit per kilogram (IU/kg) intravenous (IV) QW	Drug: Efanesoctocog alfa; Pharmaceutical form:Lyophilized powder in a sterile vial that requires reconstitution with sterile water for injection (diluent)-Route of administration:Intravenous; Other Names: BIVV001; ALTUVIIIO®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of joints with improvement in the Hemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) synovitis domain score	HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment.	From Baseline up to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the distribution of joint HEAD-US synovitis score	HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment.	From Baseline up to Week 52
Number of joints with the HEAD-US synovitis domain score that has remained unchanged or worsened	HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment.	From Baseline up to Week 52
Percentage of joints with the HEAD-US synovitis domain score that has remained unchanged or worsened	HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment.	From Baseline up to Week 52
Number of index joint type with the HEAD-US synovitis domain score that has improved, remained unchanged, or worsened	HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment.	From Baseline up to Week 52
Percentage of index joint type with the HEAD-US synovitis domain score that has improved, remained unchanged, or worsened	HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment.	From Baseline up to Week 52
Number of participants with at least 1 joint with the HEAD-US synovitis domain score that has improved, remained unchanged, or worsened	HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment.	From Baseline up to Week 52
Percentage of participants with at least 1 joint with the HEAD-US synovitis domain score that has improved, remained unchanged, or worsened	HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment.	From Baseline up to Week 52
Change from baseline in average HEAD-US synovitis domain score across all index joints	HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment.	From Baseline up to Week 52
Change from baseline in total/ domain scores of the HEAD-US	HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment.	From Baseline up to Week 26
Change from baseline in total/domain scores of the HJHS	HJHS comprises an assessment of specific features, or items, of the 6 index joints and an assessment of global gait. For each of the 6 joints, the following items are scored: swelling (0 to 3), duration of swelling (0 to 1), muscle atrophy (0 to 2), crepitus on motion (0 to 2), flexion loss (0 to 3), extension loss (0 to 3), joint pain (0 to 2), and strength (0 to 4). The maximum score for an individual index joint is 20. Gait is scored from 0 to 4. The maximum HJHS total score is 124, with a higher score indicating worse joint health.	From Baseline up to Week 26
Change from baseline in total/domain scores of the HJHS	HJHS comprises an assessment of specific features, or items, of the 6 index joints and an assessment of global gait. For each of the 6 joints, the following items are scored: swelling (0 to 3), duration of swelling (0 to 1), muscle atrophy (0 to 2), crepitus on motion (0 to 2), flexion loss (0 to 3), extension loss (0 to 3), joint pain (0 to 2), and strength (0 to 4). The maximum score for an individual index joint is 20. Gait is scored from 0 to 4. The maximum HJHS total score is 124, with a higher score indicating worse joint health.	From Baseline up to Week 52
Change from baseline in total/ domain scores of magnetic resonance imaging (MRI)	MRI will be used to detect changes in synovial hypertrophy in index joints of participants.	From Baseline up to Week 52
Change from baseline in patient-reported outcome (PRO)	Change from baseline in PRO will be assessed by the EQ-5D 5-level (EQ-5D-5L), Patient-Reported Outcomes Measurement Information System - Short Form (PROMIS-SF) version 2.0 Pain Intensity 3a, PROMIS-SF version 1.1 Pain Interference 6a, and PROMIS-SF version 2.0 Physical Function 6b.	From Baseline up to Week 52
Patient reported treatment preference and satisfaction	Patient reported treatment preference and satisfaction will be assessed through surveys and exit interviews.	At Week 52
Change from baseline in annualized bleeding rate (ABR) (spontaneous, traumatic)	The ABR will be defined as (number of bleeding episodes occurring during the treatment period)/(duration of the treatment period [days]) × 365.25.	At Week 52
Change from baseline in annualized joint bleeding rate (AjBR) (spontaneous, traumatic)	The AjBR will be defined as (number of joint bleeding episodes occurring during the treatment period)/(duration of the treatment period [days]) × 365.25.	At Week 52
Change from baseline in target joint resolution, recurrence, or development	Change from baseline in target joint resolution, recurrence, or development will be assessed.	At Week 52
The occurrence of Adverse Events (AEs), all AEs leading to treatment discontinuation, Serious Adverse Events (SAEs), and Adverse Event of Special Interest (AESIs)	The safety and tolerability of efanesoctocog alfa evaluated in all participants	Up to Week 52

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

Helpful Links

• LPS18168 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2025
• Primary Completion (Estimated): October 25, 2027
• Study Completion (Estimated): October 25, 2027

Study Registration Dates

• First Submitted: April 16, 2025
• First Submitted That Met QC Criteria: April 16, 2025
• First Posted (Actual): April 24, 2025

Study Record Updates

• Last Update Posted (Actual): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia A; BIVV001
• Other Study ID Numbers: LPS18168; U1111-1311-1701 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No