A 24-month study evaluating physical activity and joint health in patients 12 years and older, with severe haemophilia A treated once weekly with efanesoctocog alfa.

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] - Hemic and Lymphatic Diseases [C15]

Trial duration

20 Jun 2023 → ongoing

Decision date (initial)

2023-03-02

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Prophylaxis, Therapy, Safety

To describe the change from baseline in physical activity over a 24-month prospective period on once weekly prophylactic treatment with efanesoctocog alfa

Secondary objectives 6

1. Physical activity • To describe the relationship between physical activities and other variables (bleeds, joint status, pain, injuries, and Quality of Life)
2. Joint & musculoskeletal status • To describe changes from baseline in joint and musculoskeletal status
3. Efanesoctocog alfa efficacy • To describe the efficacy of efanesoctocog alfa as prophylactic treatment • To describe efanesoctocog alfa consumption for the prevention and treatment of bleeding episodes
4. PROs • To describe changes from baseline in patient reported outcome (PRO) measurements
5. Safety • To describe the safety and tolerability of efanesoctocog alfa
6. Healthcare resources • To describe healthcare resource use

Conditions and MedDRA coding

Haemophilia A

Study design 1 period

Regulatory references

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to anonymized patient level data. Data access will be granted in response to qualified research requests. All requests are evaluated by a cross functional panel of experts within Sobi. Further details on Sobi's data sharing criteria and process for requesting access can be found at: https://www.sobi.com/en/policies

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. A patient must fulfil the following criteria in order to be included in the study: 1. Be equal to or greater than 12 years of age at time of signing the informed consent.
2. 2. Male or female with severe haemophilia A diagnosis, defined as <1 IU/dL endogenous FVIII activity.
3. 3. Previous treatment for haemophilia A with any marketed recombinant and/or plasma-derived FVIII for at least 150 EDs
4. 4. Having received prophylactic treatment per local label for at least 12 months with any marketed FVIII and/or emicizumab preceding enrolment. Emicizumab prophylaxis must be stopped at least 26 weeks prior to enrolment to allow for a washout period. During this period, prophylaxis with marketed FVIII product should be used.
5. 5. Having 12 months documented pre-study treatment data regarding prophylactic treatment prescriptions and 6 months data on bleeding episodes prior to baseline visit.
6. 6. Platelet count ≥100 000 cells/µL at screening
7. 7. A patient known to be HIV antibody positive, either previously documented or identified from screening assessments, must have the following results prior to enrolment: a. CD4 lymphocyte count >200 cells/mm3 b. Viral load of <400 copies/mL c. Documented results of CD4 lymphocyte count and viral load will be accepted if samples were collected within 26 weeks prior to screening or if samples were collected during screening and evaluated by central laboratory
8. 8. Willingness and ability to complete training in the use of the study ePD and to use the ePD in their own smartphone/tablet throughout the study
9. 9. Willingness and ability to use the activity tracker (fitbit) provided by the sponsor to measure physical activity and heart rate
10. 10. Be able and willing to administer efanesoctocog alfa intravenously at home.
11. 11. Female patient is eligible to participate if she is not pregnant or breastfeeding. WOCBP shall be using an acceptable contraceptive method (see section Appendix 3) during the intervention period until the Safety follow-up call/visit. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study drug. A WOCBP must have a negative highly sensitive serum pregnancy test performed at the screening visit. Additional requirements for pregnancy testing are described in Appendix 4.
12. 12. Signed and dated informed consent provided by the patient, or the patient’s legally authorized representative(s) for patients under the legal age before any study-related activities are undertaken. Assent should be obtained from paediatric patients according to local legislation.

Exclusion criteria 4

1. The presence of any of the following will exclude a patient from inclusion in the study: 1. Medical conditions 1.1. Any concurrent clinically significant liver disease that, in the opinion of the Investigator, would make the patient unsuitable for enrolment. This may include, but is not limited to cirrhosis, portal hypertension, hepatic encephalopathy and acute hepatitis 1.2. Serious musculoskeletal and/or neurological impairment limiting the mobility and the physical ability to a degree that makes the patient unsuitable for the study as judged by the investigator 1.3. Serious active bacterial or viral infection (other than chronic hepatitis or HIV) present within 30 days of screening 1.4. Other known coagulation disorder(s) in addition to haemophilia A 1.5. History of hypersensitivity or anaphylaxis associated with any FVIII product 1.6. History of a positive inhibitor test defined as ≥0.6 BU/mL, or any value greater than or equal to the lower sensitivity cut-off for laboratories with cut-offs for inhibitor detection between 0.7 and 1.0 BU/mL, or clinical signs or symptoms of decreased response to FVIII administrations. Family history of inhibitors will not exclude the patient. 1.7. Positive inhibitor result (assessed by central laboratory), defined as ≥0.6 BU/mL at screening or baseline (see section 6.6.6.1). 1.8. Abnormal renal function, defined as serum creatinine >2.0 mg/dL taken at screening 1.9. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 x upper limit of normal (ULN), taken at screening 1.10. Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study
2. 2. Prior therapy 2.1. Vaccination within 15 days prior to the screening visit and during the run-in period 2.2. Treatment with acetylsalicylic acid within 2 weeks prior to screening 2.3. Treatment with NSAIDs above the maximum dose specified in the prescribing information within 2 weeks prior to screening 2.4. Systematic treatment within 12 weeks prior to screening with chemotherapy and/or other immunosuppressive drugs (except for the treatment of HCV or HIV). Use of corticosteroids is allowed, except for systemic corticosteroid treatment given daily or alternate days for >14 days. Local, topical, and/or inhaled steroid use is permitted
3. 3. Prior clinical study experience 3.1. Previous enrolment in this study; patients who fail screening may re-screen (one time) 3.2. Treatment with an investigational product within 30 days or 5.5 half-lives prior to screening, whichever is longer. For investigational products with a pharmacodynamic effect that persists longer than the half-life, the maximal pharmacodynamic effect must return to baseline prior to screening.
4. 4. Others 4.1. Major surgery within 12 weeks prior to screening or planned major orthopaedic surgery to occur during the study 4.2. Patients not suitable for participation, whatever reason, as judged by the investigator, including medical or clinical conditions, or patients potentially at risk of noncompliance to study procedures. 4.3. Patients are dependent on the sponsor or investigator (in conjunction with Section 1.61 of the ICH-GCP Ordinance E6) 4.4. Patients are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals 4.5. At baseline visit, patients who have not been compliant in using the activity tracker. For minimum requirements see section 6.4.6.2

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in IPAQ scoring [at month 24]

Secondary endpoints 8

1. Physical activity • Change from baseline in IPAQ scoring [at month 12] • IPAQ score • Change in mean daily minutes of tracker-recorded physical activity • Mean daily minutes of tracker-recorded physical activity
2. • Change in patient-reported workout • Change in tracker-recorded workout • Mean value in patient-reported workout • Mean value in tracker-recorded workout • Change in mean daily number of tracker-recorded steps
3. • Mean daily number of tracker-recorded steps • Achieving WHO-recommended levels (33) of tracker-recorded MVPA • Occurrence of bleeds • Occurrence of pain • Occurrence of injuries • Occurrence of bleeding episodes impacting daily activity (Missed work/school, missed other activities, nothing missed)
4. Joint & musculoskeletal status • Change from baseline in HJHS and HEAD-US and MRI at a total/joint and item domain level. • Target joint development, resolution and recurrence
5. Efanesoctocog alfa efficacy • Number of bleeding episodes • ABR by type and location • Total annualized efanesoctocog alfa consumption • Number of injections and dose to treat a bleeding episode
6. PROs • Pain (ePD reported, PROMIS Pain Intensity, PROMIS-SF Pain Interference) • QoL assessed by EQ-5D-5L • Treatment Preference Survey [EoS]
7. Safety • The occurrence of AEs and SAEs • The occurrence of clinically significant changes from baseline in physical examination • Development of inhibitors (neutralizing antibodies directed against factor VIII [FVIII]) as determined via the Nijmegen modified Bethesda assay • The occurrence of thrombotic and embolic events
8. Healthcare Resources • Number and duration of non-study medical care encounters (outpatient, inpatient, emergency room)

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

Tomtebodavagen 23A

City

Solna

Postcode

171 65

Country

Sweden

Scientific contact point

Organisation

Swedish Orphan Biovitrum AB (publ)

Contact name

Elena Santagostino

Public contact point

Organisation

Swedish Orphan Biovitrum AB (publ)

Contact name

Sofia Bergenstråle

Third parties 12

Locations

14 EU/EEA countries · 31 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 293 files

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

Application history

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