Haemophilia A (Moderate or Severe)Phase 4NCT06752850
A Study to Investigate the Course of Synovial Hypertrophy in Patients With Haemophilia A on Efanesoctocog Alfa Prophylaxis
A Phase 4 study testing Efanesoctocog alfa in people with Haemophilia A (Moderate or Severe) and Hemophilia, Classic, run by Swedish Orphan Biovitrum at 10 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Haemophilia A (Moderate or Severe), Hemophilia, Classic, Haemophilia
- What is being tested?
- Efanesoctocog alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 10 sitesin 4 countries
- Study dates
- 19 Dec 2024to 28 Dec 2026
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
- 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.
- 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.
- Must have received prophylactic treatment per local label with any marketed FVIII product or emicizumab for ≥12 months prior to the Baseline Visit.
- Have at least one eligible index joint (ankle, elbow, knee).
- Have 12 months of documented pre-study treatment data on haemophilia prescriptions and on treated bleeding episodes prior to the Baseline Visit.
- 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.
Who cannot join
- Blood clotting disorders other than haemophilia A
- Already on efanesoctocog alfa treatment
- Positive inhibitor result (assessed by local laboratory) from the Screening Visit, defined as ≥0.6 Bethesda units (BU)/mL.
- History of inhibitors without successful immune tolerance induction (ITI)
- Successful ITI is defined as:
- Negative inhibitor titer (<0.6 BU/mL)
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- FVIII recovery > 66% of expected
- FVIII half-life ≥ 6 hours
- ITI performed within the last 2 years prior to the Baseline Visit.
- Currently receiving treatment with any of the prohibited concomitant medications, as specified by the protocol.
- Planned major orthopaedic procedure in any eligible index joint during the course of the study.
- Patients are not eligible for participation in the study if they cannot undergo MRI assessments at the Baseline Visit.
- Patients with known hypersensitivity to the active substance or to any of the excipients.
- 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.
- Enrolment in a concurrent clinical interventional study, or intake of an investigational medicinal product (IMP), within 3 months prior to inclusion in the study.
Trial locations and contacts
10 sites in 4 countries.
10 sites in 4 countries
Spain4 sites
Sobi Investigational Site
Barcelona
Sobi Investigational Site
Madrid
Sobi Investigational Site
Seville
Sobi Investigational Site
Valencia
Italy3 sites
Sobi Investigational Site
Milan
Sobi Investigational Site
Naples
Sobi Investigational Site
Rozzano
Sweden2 sites
Sobi Investigational Site
Gothenburg
Sobi Investigational Site
Malmö
About this study
Official title: 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.
Read the 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.
- Conditions
- Haemophilia A (Moderate or Severe), Hemophilia, Classic, Haemophilia, Hemophilia, Classic Hemophilia, Synovial Hypertrophy
- Being tested
- Efanesoctocog alfa
- Keywords
- Deficiency, Factor VIII, Factor 8 Deficiency, Congenital, Factor VIII Deficiency, Factor VIII Deficiency, Congenital, Hemophilia A, Congenital, Synovial Membrane, Joint, Prophylaxis
- Medical subject headings
- Hemophilia A, Lymphoma, Follicular, Synovitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Efanesoctocog alfaDrug
50 IU/kg once weekly, Intravenous injection
| Study group | Role | What they receive |
|---|---|---|
| Study Treatment Group | Experimental | Not described Receives: Drug: Efanesoctocog alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline to 12 months
Secondary outcomes (12)
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to 12 months
Change in annualized bleeding rate (ABR) and annualized joint bleeding rate (AjBR) (spontaneous, traumatic).
Measured: 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).
Measured: 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.
Measured: 12 month
Qualitative Exit Interview
60-minute Telephone Interview patient reported preference for treatment.
Measured: Within 14 days after EoT Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2024
- Study start19 Dec 2024
- Primary completion17 Nov 2026 (estimated)
- Study completion28 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Haemophilia A (Moderate or Severe)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swedish Orphan Biovitrum
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PSI CRO
- Responsible party
- Sponsor
- Investigators
- Study Physician, Study director, Sobi AB
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06752850
- Sponsor's protocol ID
- Sobi.BIVV001-004
- Other IDs
- 2024-512066-33-00
- Status last verified
- Apr 2026
- First submitted
- 18 Dec 2024
- Last updated
- 30 Apr 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.