A study to investigate the course of synovial hypertrophy in patients with haemophilia A on efanesoctocog alfa prophylaxis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Swedish Orphan Biovitrum AB (publ)

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

19 Dec 2024 → ongoing

Decision date (initial)

2024-11-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Swedish Orphan Biovitrum (Publ)

External identifiers

EU CT number

2024-512066-33-00

WHO UTN

U1111-1304-5512

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Therapy, Efficacy, Safety

To assess the improvement of existing synovial hypertrophy in joints of patients receiving efanesoctocog alfa prophylaxis

Secondary objectives 6

1. To assess the incidence of synovial hypertrophy in joints of patients receiving efanesoctocog alfa prophylaxis
2. To assess the joint health status during 12 months of prophylaxis with efanesoctocog alfa
3. To assess health-related outcomes of patients during 12 months of prophylaxis with efanesoctocog alfa
4. To assess the preference for efanesoctocog alfa treatment
5. To assess efficacy of efanesoctocog alfa prophylaxis during 12 months
6. To assess safety of efanesoctocog alfa

Conditions and MedDRA coding

Haemophilia A

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and 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 11

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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Joints with synovial hypertrophy at baseline (HEAD-US synovial hypertrophy domain score of 1 or 2) and at least 1 point decrease in HEAD-US synovial hypertrophy domain score at Month 12 (Yes/No)

Secondary endpoints 11

1. Joints with no synovial hypertrophy at baseline (HEAD-US synovial hypertrophy domain score 0) and at least 1 point increase in HEAD-US synovial hypertrophy domain score at Month 6 or Month 12 (Yes/No)
2. Distribution of joint HEAD-US synovial hypertrophy domain scores 0/1/2 at baseline and at Months 6 and 12
3. Change from baseline in total/domain scores of HEAD-US per patient and per joint at Months 6 and 12
4. Change from baseline in total/domain scores of International Prophylaxis Study Group (IPSG) MRI per patient and per joint at Month 12
5. Change from baseline in total/domain scores of HJHS per patient and per joint at Month 12
6. Patients with improved, unchanged, or worsened total/domain HEAD-US/MRI/HJHS scores at Month 12 from baseline
7. Changes in PROs from baseline to Month 6 and Month 12 (assessed by 5- level EuroQol-5 dimensions [EQ-5D-5L], Patient-Reported Outcomes Measurement Information System [PROMIS] pain intensity, PROMIS pain interference, and PROMIS physical function)
8. Patient-reported treatment preference at Month 12 (assessed with a questionnaire and exit interview)
9. Change in ABR and annualized joint bleeding rate (AjBR) (spontaneous, traumatic) based on treated bleeds from the retrospective data collection period to on-study period
10. Patients with target joint resolution or development from baseline to Month 12
11. The occurrence of treatment-emergent adverse events (TEAEs) leading to treatment discontinuation, serious TEAEs, and adverse events of special interest (AESIs)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Swedish Orphan Biovitrum AB (publ)

Sponsor organisation

Swedish Orphan Biovitrum AB (publ)

Address

-

City

Stockholm

Postcode

112 76

Country

Sweden

Scientific contact point

Organisation

Swedish Orphan Biovitrum AB (publ)

Contact name

Contact point

Public contact point

Organisation

Swedish Orphan Biovitrum AB (publ)

Contact name

Contact point

Third parties 5

Locations

4 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 50 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications