Clinical trial NCT05817812: A Study Evaluating Physical Activity and Joint Health in Severe Haemophilia A Patients ≥12 Years Treated Once Weekly With Efanesoctocog Alfa
Official title: A Phase 3b Open-label Study Evaluating Physical Activity and Joint Health in Previously Treated Patients ≥12 Years With Severe Haemophilia A Treated With Recombinant Coagulation Factor VIII Fc-von Willebrand Factor-XTEN Fusion Protein (Efanesoctocog Alfa) for 24 Months
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hemophilia A, Severe
Keywords: Blood coagulation disorder
Coagulation protein disorder
Haemophilia
FVIII
Efanesoctocog alfa
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2023-04-18
Enrollment: 93
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: FREEDOM is a multicentre, open-label, single-arm, phase 3b study in Europe that aims to enrol approximately 90 previously treated severe haemophilia A patients aged ≥12 years, currently on prophylaxis. After a run-in period of 30-45 days, patients will receive efanesoctocog alfa prophylaxis, 50 IU/kg once-weekly for 24 months (additional preventive dose not permitted). An activity tracker and an electronic patient diary will be used to collect data on physical activity, bleeds, factor dosing, pain, and injuries from screening throughout the study.

The primary objective is to describe changes in physical activities over 24 months on efanesoctocog alfa prophylaxis, with a primary endpoint of change from baseline in International Physical Activity Questionnaire (IPAQ) at month 24.

Secondary objectives include relationship between physical activity and other variables (bleeds, joint status, pain, injuries, and quality of life); changes in joint status as assessed by HEAD-US, HJHS and MRI; occurrence of bleeds, injuries, pain. Safety and tolerability of efanesoctocog alfa will also be evaluated.


Eligibility criteria: Key Inclusion Criteria:

* Previous treatment for haemophilia A with any marketed recombinant and/or plasma-derived FVIII for at least 150 EDs.
* Having received prophylactic treatment with any marketed recombinant and/or plasma FVIII or emicizumab per local label for at least 12 months preceding enrolment.
* Having 12 months documented pre-study treatment data regarding prophylactic treatment prescriptions and 6 months data on bleeding episodes prior to baseline visit.
* Willingness and ability to complete training in the use of the study ePD and to use the ePD in their own smartphone throughout the study.
* Willingness and ability to use the activity tracker provided by the sponsor to measure physical activity and heart rate.
* Be able and willing to administer efanesoctocog alfa intravenously at home.

Key Exclusion Criteria:

* 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.
* Other known coagulation disorder(s) in addition to haemophilia A.
* History and/or current positive inhibitor test defined as ≥0.6 BU/mL.
* Treatment with NSAIDs above the maximum dose specified in the prescribing information within 2 weeks prior to screening.
* Systematic treatment within 12 weeks prior to screening with chemotherapy and/or other immunosuppressive drugs.
* Treatment with an investigational product within 30 days or 5.5 half-lives prior to screening, whichever is longer.
* Major surgery within 12 weeks prior to screening or planned major orthopaedic surgery to occur during the study.
* At baseline visit, patients who have not been compliant in using the activity tracker.

Primary outcomes:
measure: Change from baseline in International Physical Activity Questionnaire (IPAQ) scoring
timeFrame: Baseline and month 24
Secondary outcomes:
measure: Change from baseline in International Physical Activity Questionnaire (IPAQ) scoring
timeFrame: Baseline and month 12
measure: International Physical Activity Questionnaire (IPAQ) score
timeFrame: Baseline, month 6, 12, 18 and 24
measure: Change in mean daily minutes in physical activity
timeFrame: Run-in month, month 12 and 24
measure: Mean daily minutes of physical activity
timeFrame: Per 6-month period
measure: Change in type of workouts
timeFrame: Run-in month, month 12 and 24
measure: Change in frequency of workouts
timeFrame: Run-in month, month 12 and 24
measure: Change in duration of workouts
timeFrame: Run-in month, month 12 and 24
measure: Change in patient reported intensity of workouts
timeFrame: Run-in month, month 12 and 24
measure: Change in tracker recorded intensity of workouts
timeFrame: Run-in month, month 12 and 24
measure: Mean value of patient and tracker reported type of workouts
timeFrame: Per 6-month period
measure: Mean value of frequency of workouts
timeFrame: Per 6-month period
measure: Mean value of duration of workouts
timeFrame: Per 6-month period
measure: Mean value of patient reported intensity of workouts
timeFrame: Per 6-month period
measure: Mean value of tracker recorded intensity of workouts
timeFrame: Per 6-month period
measure: Change in mean daily number of steps
timeFrame: Run-in month, month 12 and 24
measure: Mean daily number of steps
timeFrame: Per 6-month period
measure: Achieving WHO-recommended levels of MVPA
timeFrame: Run-in month, month 12 and 24
measure: Occurrence of bleeds in relation to workouts
timeFrame: Baseline to month 24
measure: Occurrence of pain in relation to workouts
timeFrame: Baseline to month 24
measure: Occurrence of injuries in relation to workouts
timeFrame: Baseline to month 24
measure: Occurrence of bleeding episodes impacting daily activity
timeFrame: Baseline to month 24
measure: Change from baseline in Haemophilia Joint Health Score (HJHS) score
timeFrame: Baseline, month 6, 12, 18, 24
measure: Change from baseline in Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US)
timeFrame: Baseline, month 12 and 24
measure: Change from baseline in haemophilic arthropathy assessed by the International Prophylaxis Study Group (IPSG) Magnetic Resonance Imaging (MRI) scale
timeFrame: Baseline, month 24
measure: Target joint development (three or more spontaneous bleeds into a single joint within a consecutive 6-month period)
timeFrame: Month 6, 12, 18, 24
measure: Target joint resolution ( ≤2 bleeds into the joint within a consecutive 12-month period the joint is no longer considered a target joint)
timeFrame: Month 6, 12, 18, 24
measure: Target joint recurrence (≥3 spontaneous bleeds in a single joint within any consecutive 6-month period after target joint resolution)
timeFrame: Month 6, 12, 18, 24
measure: Number of bleeding episodes
timeFrame: Per 6-month period and cumulative
measure: Annualized bleeding rate (ABR)
timeFrame: Baseline to month 24
measure: Total annualized efanesoctocog alfa consumption
timeFrame: Baseline to month 24
measure: Number of injections and dose to treat a bleeding episode
timeFrame: Baseline to month 24
measure: Pain reported via electronic patient diary
timeFrame: Baseline to month 24
measure: Pain intensity reported in the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale - Pain Intensity 3a
timeFrame: Baseline, month 6, 12, 18, 24
measure: Pain interference reported in the Patient-Reported Outcomes Measurement Information System (PROMIS) scale - Pain interference 6a
timeFrame: Baseline, month 6, 12, 18, 24
measure: Quality of life assessed by EuroQoL 5-dimension 5-level (EQ-5D-5L)
timeFrame: Baseline, month 6, 12, 18, 24
measure: Assessment of treatment preference
timeFrame: 24 months
measure: The occurrence of adverse events and serious adverse events
timeFrame: From screening to month 24
measure: The occurrence of clinically significant changes
timeFrame: Baseline, month 6, 12, 18, 24
measure: Development of inhibitors (neutralizing antibodies directed against FVIII)
timeFrame: Baseline, month 6, 12, 18, 24
measure: The occurrence of thrombotic and embolic events
timeFrame: From screening to month 24
measure: Number of non-study medical care encounters
timeFrame: From baseline to month 24
measure: Duration of non-study medical care encounters
timeFrame: From baseline to month 24
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Investigational Site
city: Zagreb
country: Croatia
facility: Investigational Site
city: Brno
country: Czechia
facility: Investigational Site
city: Praha
country: Czechia
facility: Investigational Site
city: Bordeaux
country: France
facility: Investigational Site
city: Le Kremlin-Bicêtre
country: France
facility: Investigational Site
city: Marseille
country: France
facility: Investigational Site
city: Strasbourg
country: France
facility: Investigational Site
city: Berlin
country: Germany
facility: Investigational Site
city: Frankfurt
country: Germany
facility: Investigational Site
city: Gießen
country: Germany
facility: Investigational Site
city: Hamburg
country: Germany
facility: Investigational Site
city: Athens
country: Greece
facility: Investigational Site
city: Dublin
country: Ireland
facility: Investigational Site
city: Catanzaro
country: Italy
facility: Investigational Site
city: Florence
country: Italy
facility: Investigational Site
city: Naples
country: Italy
facility: Investigational Site
city: Parma
country: Italy
facility: Investigational Site
city: Rome
country: Italy
facility: Investigational Site
city: Utrecht
country: Netherlands
facility: Investigational Site
city: Oslo
country: Norway
facility: Investigational Site
city: Ljubljana
country: Slovenia
facility: Investigational Site
city: Barcelona
country: Spain
facility: Investigational Site
city: Madrid
country: Spain
facility: Investigational Site
city: Oviedo
country: Spain
facility: Investigational Site
city: Lund
country: Sweden
facility: Investigational Site
city: Solna
country: Sweden
facility: Investigational Site
city: Canterbury
country: United Kingdom
facility: Investigational Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: Investigational Site
city: Oxford
country: United Kingdom
facility: Investigational Site
Study officials:
affiliation: Swedish Orphan Biovitrum AB
name: Study Physician, MD, PhD
role: STUDY_DIRECTOR
References: