A Study to Investigate the Course of Synovial Hypertrophy in Patients With Haemophilia A on Efanesoctocog Alfa Prophylaxis

A 12-month, Interventional, Open-label, Phase 4 Study in Europe (SHINE) to Investigate the Course of Synovial Hypertrophy as Detected by Joint Ultrasound and MRI in Patients With Haemophilia A on Efanesoctocog Alfa Prophylaxis.

The rationale for conducting this open-label phase 4 study is to assess whether once-weekly prophylaxis with efanesoctocog alfa (50 IU/kg) improves the disease course of existing synovial hypertrophy and prevents the risk of joint bleeds in patients with moderate or severe haemophilia A. The use of imaging assessments will allow for objective detection and monitoring of synovial hypertrophy, and thus expand on the previous findings demonstrating positive effects of once-weekly prophylaxis with efanesoctocog alfa (50 IU/kg) on joint health.

Study Overview

• Status: Active, not recruiting
• Conditions: Hemophilia; Haemophilia; Classic Hemophilia; Haemophilia A (Moderate or Severe); Hemophilia, Classic; Synovial Hypertrophy
• Intervention / Treatment: Drug: Efanesoctocog alfa

Detailed Description

This is a 12-month, multicentre, open-label, non-randomized, interventional single-arm study to assess the course of synovial hypertrophy in previously treated patients ≥12 years of age with moderate or severe haemophilia A achieving high sustained FVIII levels provided by weekly efanesoctocog alfa prophylaxis. To be eligible to enroll in the study, patients must have existing synovial hypertrophy in at least one of the 6 index joints (ankles, elbows, and knees) as assessed by the HEAD-US scoring system. A retrospective data collection on patients' haemophilia, medical, and surgical history will be performed, including a 12-month history of previous treatment and treated bleeding episodes.

The study will start with the Screening Visit, which can be conducted up to 45 days prior to the Baseline Visit (Day 1), to check whether the patient fulfils all the inclusion criteria and none of the exclusion criteria. Patients will have an ultrasound examination of all non-prosthetic index joints at screening. The ultrasound images will be sent for central reading assessment using the HEAD-US scoring system to determine whether the patient has at least one eligible joint required for study inclusion. Once it is confirmed that a patient is eligible for inclusion, he/she will be enrolled in the study and attend a mix of on-site visits and phone call visits. The results from central reading assessment will be sent to the study sites and included in the baseline characteristics of the patients. MRI examinations can be conducted at the Baseline Visit or up to 28 days afterwards. Images from MRI will also be sent for central reading assessment using the International Prophylaxis Study Group (IPSG) MRI scale. The central reading assessment will be sent to the study sites and included in the patient data. Patients will be treated with once-weekly efanesoctocog alfa (50 IU/kg) prophylaxis and will complete the patient diary with their dosing and bleeding information. Assessments will be conducted during the on-site visits, which will occur every 6 months, and during phone call visits, which will occur halfway between these visits. A Safety Follow-up Call will be conducted 14 (+7) days after the End of Treatment (EoT) Visit. Ultrasound and MRI will be used to detect changes in synovial hypertrophy in index joints of patients. The primary endpoint of improvement in existing synovial hypertrophy from baseline to Month 12 as well as the key secondary endpoint of detection of new synovial hypertrophy and change in joint health status from baseline to Month 6 or Month 12 will be assessed using ultrasound and the HEAD-US scoring system.

To obtain 100 eligible index joints, the target is to enroll approximately 35 patients.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy
    • Sobi Investigational Site
  • Naples, Italy
    • Sobi Investigational Site
  • Rozzano, Italy
    • Sobi Investigational Site
• Norway
  • Oslo, Norway
    • Sobi Investigational Site
• Spain
  • Barcelona, Spain
    • Sobi Investigational Site
  • Madrid, Spain
    • Sobi Investigational Site
  • Seville, Spain
    • Sobi Investigational Site
  • Valencia, Spain
    • Sobi Investigational Site
• Sweden
  • Gothenburg, Sweden
    • Sobi Investigational Site
  • Malmö, Sweden
    • Sobi Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. Parents' or legally designated representatives' consent is required for patients who are <18 years of age or unable to give consent, or as applicable per local laws. Patients who are <18 years of age should provide assent in addition to the parents'/legally designated representatives' consent, if appropriate.
2. Male or female patients who are ≥12 years of age and diagnosed with moderate or severe haemophilia A (defined as ≤5% of normal FVIII clotting activity) at the time of signing the ICF.
3. A female patient is eligible to participate if she is not pregnant at enrolment and does not plan to become pregnant during the study. A woman of child-bearing potential (WOCBP) must have a negative highly sensitive serum pregnancy test at the Screening Visit.
4. Must have received prophylactic treatment per local label with any marketed FVIII product or emicizumab for ≥12 months prior to the Baseline Visit.
5. Have at least one eligible index joint (ankle, elbow, knee).
6. Have 12 months of documented pre-study treatment data on haemophilia prescriptions and on treated bleeding episodes prior to the Baseline Visit.
7. Willingness and the ability of the patient or their legally designated representative to complete training in the use of the study patient diary and to complete the diary throughout the study.

Exclusion Criteria:

1. Blood clotting disorders other than haemophilia A
2. Already on efanesoctocog alfa treatment
3. Positive inhibitor result (assessed by local laboratory) from the Screening Visit, defined as ≥0.6 Bethesda units (BU)/mL.

4. History of inhibitors without successful immune tolerance induction (ITI)

   • Successful ITI is defined as:
   • Negative inhibitor titer (<0.6 BU/mL)
   • FVIII recovery > 66% of expected
   • FVIII half-life ≥ 6 hours
5. ITI performed within the last 2 years prior to the Baseline Visit.
6. Currently receiving treatment with any of the prohibited concomitant medications, as specified by the protocol.
7. Planned major orthopaedic procedure in any eligible index joint during the course of the study.
8. Patients are not eligible for participation in the study if they cannot undergo MRI assessments at the Baseline Visit.
9. Patients with known hypersensitivity to the active substance or to any of the excipients.
10. Patient 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.
11. Enrolment in a concurrent clinical interventional study, or intake of an investigational medicinal product (IMP), within 3 months prior to inclusion in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Treatment Group	Drug: Efanesoctocog alfa; 50 IU/kg once weekly, Intravenous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) synovial hypertrophy domain score decrease.	At least 1 point decrease in HEAD-US synovial hypertrophy domain score at Month 12 (for joints with a domain score of 1 or 2 at baseline).	Baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) synovial hypertrophy domain score increase.	At least 1 point increase in HEAD-US synovial hypertrophy domain score at Month 6 or Month 12 for joints with no synovial hypertrophy at baseline (domain score of 0).	Baseline to 6 or 12 months
International Prophylaxis Study Group (IPSG) magnetic resonance imaging (MRI)	Change from baseline in total/domain scores of International Prophylaxis Study Group (IPSG) MRI per patient and per joint at Month 12.	Baseline to 12 months
Haemophilia Joint Health Score (HJHS)	Change from baseline in total/domain scores of HJHS per patient and per joint at Month 12.	Baseline to 12 months
Patient Reported Outcome (PRO) of Pain Intensity	Use of PROMIS SF v2.0 to measure change in patient-reported pain intensity from baseline.	Baseline to 6 month and 12 months
Patient Reported Outcome of Pain Interference	Use of PROMIS SF v2.0 to measure change in patient-reported pain interference from baseline.	Baseline to 6 month and 12 months
Patient Reported Outcome of Physical Function	Use of PROMIS SF v2.0 to measure change in patient-reported physical function from baseline.	Baseline to 6 month and 12 months
Patient Reported Outcome of 5-level EuroQol-5 dimensions [EQ-5D-5L] score	Changes from baseline of patient self-care, usual activities, pain/discomfort, anxiety/depression.	Baseline to 6 month and 12 months
Hemo-FAST scoring	Assess functional mobility in PWH. The Hemo-Fast tool is comprised of the Patient-reported outcome part and a Clinician-reported outcome (ClinRO) part, with a score of 0 to 100, with zero being the best possible joint health status. The change from baseline to month 12 will be evaluated.	Baseline to 12 months
Change in annualized bleeding rate (ABR) and annualized joint bleeding rate (AjBR) (spontaneous, traumatic).		12 months prior to on-study period (retrospective) to 12 months after start of study intervention (prospective)
The occurrence of treatment-emergent adverse events (TEAEs) leading to treatment discontinuation, serious TEAEs, and adverse events of special interest (AESIs).		12 months, +14 (+7days) after the last IMP dose
Patient-Reported Treatment Preference Questionnaire	A 2-item treatment survey developed to evaluate perceived impact of treatment.	12 month
Qualitative Exit Interview	60-minute Telephone Interview patient reported preference for treatment.	Within 14 days after EoT Visit

Collaborators and Investigators

• Sponsor: Swedish Orphan Biovitrum
• Collaborators: PSI CRO
• Investigators: Study Director: Study Physician, Sobi AB

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2024
• Primary Completion (Estimated): November 17, 2026
• Study Completion (Estimated): December 28, 2026

Study Registration Dates

• First Submitted: December 18, 2024
• First Submitted That Met QC Criteria: December 20, 2024
• First Posted (Actual): December 31, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Prophylaxis; Joint; Factor VIII Deficiency; Hemophilia A, Congenital; Deficiency, Factor VIII; Factor 8 Deficiency, Congenital; Factor VIII Deficiency, Congenital; Synovial Membrane
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Neoplasms; Joint Diseases; Genetic Diseases, Inborn; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Blood Coagulation Disorders; Lymphoma; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Lymphoma, Follicular; Hemophilia A; Synovitis
• Other Study ID Numbers: Sobi.BIVV001-004; 2024-512066-33-00 (Ctis)

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. Patient level data will be anonymized and study documents, if applicable will be redacted to protect the privacy of trial participants.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes