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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
93
Recombinant coagulation factor VIII Fc-von Willebrand Factor-XTEN fusion protein (rFVIIIFc-VWF-XTEN)
Investigational Site
Vienna, Austria
Investigational Site
Zagreb, Croatia
Investigational Site
Brno, Czechia
Investigational Site
Prague, Czechia
Investigational Site
Bordeaux, France
Investigational Site
Le Kremlin-Bicêtre, France
Investigational Site
Marseille, France
Investigational Site
Strasbourg, France
Investigational Site
Berlin, Germany
Investigational Site
Frankfurt, Germany
...and 20 more locations
Change from baseline in International Physical Activity Questionnaire (IPAQ) scoring
The IPAQ is a validated, 7-day recall questionnaire measuring current levels of physical activity. Scoring of the IPAQ results in a continuous variable in the form of total MET-minutes per week. Higher scores means higher physical activity level.
Time frame: Baseline and month 24
Change from baseline in International Physical Activity Questionnaire (IPAQ) scoring
The IPAQ is a validated, 7-day recall questionnaire measuring current levels of physical activity. Scoring of the IPAQ results in a continuous variable in the form of total MET-minutes per week. Higher scores means higher physical activity level.
Time frame: Baseline and month 12
International Physical Activity Questionnaire (IPAQ) score
The IPAQ is a validated, 7-day recall questionnaire measuring current levels of physical activity. Scoring of the IPAQ results in a continuous variable in the form of total MET-minutes per week. Higher scores means higher physical activity level.
Time frame: Baseline, month 6, 12, 18 and 24
Change in mean daily minutes in physical activity
Tracker-recorded
Time frame: Run-in month, month 12 and 24
Mean daily minutes of physical activity
Tracker-recorded
Time frame: Per 6-month period
Change in type of workouts
Patient and tracker reported
Time frame: Run-in month, month 12 and 24
Change in frequency of workouts
Patient and tracker reported
Time frame: Run-in month, month 12 and 24
Change in duration of workouts
Patient and tracker reported
Time frame: Run-in month, month 12 and 24
Change in patient reported intensity of workouts
The patient will report workouts in a patient diary and rate the intensity on a 5 level scale. The levels are: 1 = easy, 2 = moderate, 3 = slightly challenging, 4 = exhausting, 5 = very exhausting. The changes will be calculated on a intra-patient basis
Time frame: Run-in month, month 12 and 24
Change in tracker recorded intensity of workouts
The patient will be provided with an activity tracker that will automatically record workouts when the patient is wearing the tracker. The intensity levels will be based on the heart rate and will be presented on a 4 level scale. The levels are: 1 = out of range, 2 = fat burn, 3 = cardio, 4 = peak
Time frame: Run-in month, month 12 and 24
Mean value of patient and tracker reported type of workouts
Type of workout will be transcribed into a risk level of participating in a given activity for a haemophilia patient. Risk levels are based on a rating of 1-3 where level 1 represents a low risk of causing a bleeding episode and level 3 represents a high risk. The mean value will be calculated per 6-month period
Time frame: Per 6-month period
Mean value of frequency of workouts
Patient and tracker reported
Time frame: Per 6-month period
Mean value of duration of workouts
Patient and tracker reported
Time frame: Per 6-month period
Mean value of patient reported intensity of workouts
The patient will report workouts in a patient diary and rate the intensity on a 5 level scale. The levels are: 1 = easy, 2 = moderate, 3 = slightly challenging, 4 = exhausting, 5 = very exhausting. The mean value will be calculated per 6-month period
Time frame: Per 6-month period
Mean value of tracker recorded intensity of workouts
The patient will be provided with an activity tracker that will automatically record workouts when the patient is wearing the tracker. The intensity levels will be based on the heart rate and will be presented on a 4 level scale. The levels are: 1 = out of range, 2 = fat burn, 3 = cardio, 4 = peak The mean value will be calculated per 6-month period
Time frame: Per 6-month period
Change in mean daily number of steps
Tracker-recorded
Time frame: Run-in month, month 12 and 24
Mean daily number of steps
Tracker-recorded
Time frame: Per 6-month period
Achieving WHO-recommended levels of MVPA
Tracker-recorded
Time frame: Run-in month, month 12 and 24
Occurrence of bleeds in relation to workouts
Time frame: Baseline to month 24
Occurrence of pain in relation to workouts
Time frame: Baseline to month 24
Occurrence of injuries in relation to workouts
Time frame: Baseline to month 24
Occurrence of bleeding episodes impacting daily activity
Time frame: Baseline to month 24
Change from baseline in Haemophilia Joint Health Score (HJHS) score
The six index joints (elbows, knees and ankles) will be examined and scored. The minimum score per joint is 0, the maximum score is 20. In addition, Gait is scored on a scale from 0 to 4 based on the number of skills that are not within the normal limits. The total score will be the sum of scores across all six joints plus the gait score (range from 0 to 124, with 0 being normal and 124 being the most severe disease).
Time frame: Baseline, month 6, 12, 18, 24
Change from baseline in Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US)
The HEAD-US joint score will be calculated for six joints, the right and left ankle, knee, and elbow joints. The specific joint score is made up of three item scores, disease activity (synovitis), disease damage of articular surfaces, and disease damage of subchondral bone. Specific joint score is the sum of the three item scores for each specific joint. Its values range from 0 (minimum) to 8 (maximum).The total score represents the sum of item scores for abnormalities detected.
Time frame: Baseline, month 12 and 24
Change from baseline in haemophilic arthropathy assessed by the International Prophylaxis Study Group (IPSG) Magnetic Resonance Imaging (MRI) scale
The IPSG scale is made up of two subscores, one for soft-tissue changes and one for osteochondral changes. MRI joint score is the sum of the soft tissue and osteochondral subscores for each joint, ranging from 0-17 where 0 is absence of damage. MRI total score is the sum of joint scores across all joints.
Time frame: Baseline, month 24
Target joint development (three or more spontaneous bleeds into a single joint within a consecutive 6-month period)
The number and proportion of patients with target joint development and the total number of target joint developed will be assessed.
Time frame: Month 6, 12, 18, 24
Target joint resolution ( ≤2 bleeds into the joint within a consecutive 12-month period the joint is no longer considered a target joint)
The number and proportion of patients with target joint resolution and the total number of target joint resolutions will be assessed
Time frame: Month 6, 12, 18, 24
Target joint recurrence (≥3 spontaneous bleeds in a single joint within any consecutive 6-month period after target joint resolution)
The number and proportion of patients with target joint recurrence and the total number of target joint recurrence will be assessed
Time frame: Month 6, 12, 18, 24
Number of bleeding episodes
Time frame: Per 6-month period and cumulative
Annualized bleeding rate (ABR)
Time frame: Baseline to month 24
Total annualized efanesoctocog alfa consumption
Time frame: Baseline to month 24
Number of injections and dose to treat a bleeding episode
Time frame: Baseline to month 24
Pain reported via electronic patient diary
The patient will report pain (cause of pain, location and intensity. The intensity will reported as mild, moderately low, moderately high, severe and worst possible.
Time frame: Baseline to month 24
Pain intensity reported in the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale - Pain Intensity 3a
The PROMIS Pain Intensity instrument assesses pain intensity on a 5-point Likert scale, ranging from 1 (had no pain) to 5 (very severe)
Time frame: Baseline, month 6, 12, 18, 24
Pain interference reported in the Patient-Reported Outcomes Measurement Information System (PROMIS) scale - Pain interference 6a
The PROMIS Pain Interference 6a is a patient-assessed instrument and is to measure pain interference on a 5-point Likert scale, ranging from 1 (not at all) to 5 (very much)
Time frame: Baseline, month 6, 12, 18, 24
Quality of life assessed by EuroQoL 5-dimension 5-level (EQ-5D-5L)
EQ-5D-5L assess 5 dimensions of health outcome (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each of the dimensions in the EQ-5D-5L questionnaire is divided into 5 levels: * Level 1: indicating no problem * Level 2: indicating slight problems * Level 3: indicating moderate problems * Level 4: indicating severe problems * Level 5: indicating unable to/extreme problems Patients will select a level for each dimension that best describes their health status for that dimension. A 5 digit code will be obtained, made up of the response for each dimension. This code will then be converted to an index score.The EQ-5D-5L VAS is an overall assessment of health on a scale from 1-100 that the patient provides at the end of the EQ-5D-5L questionnaire. 100 represents the best health you can imagine and 0 represents the worst health you can imagine.
Time frame: Baseline, month 6, 12, 18, 24
Assessment of treatment preference
This will be assessed with the Treatment Preference Survey that consists of 2 questions on perceived impact of treatment.
Time frame: 24 months
The occurrence of adverse events and serious adverse events
Time frame: From screening to month 24
The occurrence of clinically significant changes
Assessed by physical examination, vital signs and laboratory tests
Time frame: Baseline, month 6, 12, 18, 24
Development of inhibitors (neutralizing antibodies directed against FVIII)
Determined via the Nijmegen modified Bethesda assay
Time frame: Baseline, month 6, 12, 18, 24
The occurrence of thrombotic and embolic events
Time frame: From screening to month 24
Number of non-study medical care encounters
The number and proportion of patients having non-study medical care encounter visits will be described, as well as the corresponding total number of visits.
Time frame: From baseline to month 24
Duration of non-study medical care encounters
The duration of non-study medical care encounter visits will be described.
Time frame: From baseline to month 24
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