A Proof-of-concept Study to Reduce Treatment Burden in Haemophilia Participants Receiving Factor VIII and Factor IX Infusions

Study Overview
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Brief Summary
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The main aim is to describe how the treatment burden and challenges of participants, relatives, and doctors during regular Factor VIII and Factor IX infusions to treat hemophilia evolve using a virtual-reality (VR) based solution. The study also aims to find out how well the VR based solution is tolerated and how satisfied the participants, relatives, and doctors are with it. The VR-based solution includes a mobile phone app and a 3D mask. Participants will use the VR-based solution while receiving prophylactic Factor VIII and Factor IX infusions for 4 weeks at home. Participants will visit the clinic for the last infusion; at this time data will be collected from participants, relatives, and doctors

Official Title
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Ability of a Virtual-reality Based Solution Aiming to Reduce Patient Burden Related to Repetitive Intravenous Perfusions. A Proof-of-concept Study in Hemophilia Patients Receiving Prophylactic Factor VIII or Factor IX Infusions

Conditions
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Hemophilia

Intervention / Treatment
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* Device: Virtual-reality (VR) Based Solution


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male participant over the age of 6 years, with diagnosed Congenital Hemophilia A or B, whatever the severity is Participant under long-term prophylaxis with intravenous Factor VIII or Factor IX infusions Participant (or the legal guardians if participant age <18 years) able and willing to give written informed consent and to comply with the requirements of the study protocol Participant affiliated to the national social security or beneficiary to such insurance Exclusion criteria: Participant with known or suspected hypersensitivity to virtual-reality based tools Participant with central venous line for the administration of Factor VIII or Factor IX Participant (and the legal guardians if participant age <18 years) with history of unreliability or non-cooperation (including for completion of self-reported questionnaires) Participant (and the legal guardians if participant age <18 years) with insufficient comprehension of French language Participant taking part in another clinical trial Participant deprived of his liberty by judicial or administrative order NB: participants with haemophilia A having participated in the test phase of the study could be included in the clinical study itself after a period of 4 months minimum with no use of the virtual-reality based solution.

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VR-based Experimental Group<br>Participants will receive Factor VIII or Factor IX infusion using a VR-based solution. The VR-based solution will be provided in a medical device CE marked and specifically developed by Deepsen, a French company specializing in e-health solutions to reduce pain. It includes both a mobile phone application (for an explanation on infusions) and a 3D mask to be used during infusions. | Device: Virtual-reality (VR) Based Solution<br>* VR-based solution comprises a mobile phone application including explanation on the different steps to be followed to perform infusions in satisfactory conditions, notably as regards safety, as well as VAS for pain and anxiety to be completed at each Factor VIII or Factor IX infusion between inclusion and the Week 4 visit. It also comprises a 3D mask (to be used before or during infusions) including simulation of the infusions themselves (before infusion) and a relaxing and distracting content (during and after infusions).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Anxiety of Participants and Relatives Using an Anxiety Visual Analogue Scale (A-VAS) Score Before Each Factor VIII or Factor IX Infusion | The anxiety of participants and relatives before each Factor VIII or Factor IX infusion will be measured with a 10-points VAS. The A-VAS is a 10 centimeter (cm) line with anchor statements on the left (no anxiety) and on the right (extreme anxiety). An increase in score from 0 to 10 indicates a worsening of anxiety. | Baseline up to Week 4 | 
| Percent Change from Baseline in Anxiety of Participants and Relatives Using an A-VAS Score Before Each Factor VIII or Factor IX Infusion | The anxiety of participants and relatives before each Factor VIII or Factor IX infusion will be measured with a 10-points VAS. The A-VAS is a 10 cm line with anchor statements on the left (no anxiety) and on the right (extreme anxiety). An increase in score from 0 to 10 indicates a worsening of anxiety. | Baseline up to Week 4 | 
| Number of Participants and Relatives with a Decrease of 2 Points out of 10 Points in the A-VAS Score Before Each Factor VIII or Factor IX Infusion | The A-VAS is a 10 cm line with anchor statements on the left (no anxiety) and on the right (extreme anxiety). An increase in score from 0 to 10 indicates a worsening of anxiety. The number of participants and relatives with a decrease of 2 points out of 10 points will be assessed. | Up to Week 4 | 
| Change from Baseline in Anxiety of Participants and Relatives Using an A-VAS Score After Each Factor VIII or Factor IX Infusion | The anxiety of participants and relatives after each Factor VIII or Factor IX infusion will be measured with a 10-points VAS. The A-VAS is a 10 cm line with anchor statements on the left (no anxiety) and on the right (extreme anxiety). An increase in score from 0 to 10 indicates a worsening of anxiety. | Baseline up to Week 4 | 
| Percent Change from Baseline in Anxiety of Participants and Relatives Using an A-VAS Score After Each Factor VIII or Factor IX Infusion | The anxiety of participants and relatives after each Factor VIII or Factor IX infusion will be measured with a 10-points VAS. The A-VAS is a 10 cm line with anchor statements on the left (no anxiety) and on the right (extreme anxiety). An increase in score from 0 to 10 indicates a worsening of anxiety. | Baseline up to Week 4 | 
| Number of Participants and Relatives With a Decrease of 2 Points out of 10 Points in the A-VAS Score After Each Factor VIII or Factor IX Infusion | The A-VAS is a 10 cm line with anchor statements on the left (no anxiety) and on the right (extreme anxiety). An increase in score from 0 to 10 indicates a worsening of anxiety. The number of participants and relatives with a decrease of 2 points out of 10 points will be assessed. | Up to Week 4 | 
| Change from Baseline in Pain of Participants Using Pain Visual Analogue Scale (P-VAS) Score After Each Factor VIII or Factor IX Infusion | The pain of participants after each Factor VIII or Factor IX infusion will be measured with a 10-points VAS. The P-VAS is a 10 cm line with anchor statements on the left (no pain) and on the right (extreme pain). An increase in score from 0 to 10 indicates a worsening of pain. | Baseline up to Week 4 | 
| Percent Change from Baseline in Pain of Participants Using P-VAS Score After Each Factor VIII or Factor IX Infusion | The pain of participants after each Factor VIII or Factor IX infusion will be measured with a 10-points VAS. The P-VAS is a 10 cm line with anchor statements on the left (no pain) and on the right (extreme pain). An increase in score from 0 to 10 indicates a worsening of pain. | Baseline up to Week 4 | 
| Number of Participants With a Decrease of 2 Points out of 10 Points in the P-VAS Score After Each Factor VIII or Factor IX Infusion | The P-VAS is a 10 cm line with anchor statements on the left (no pain) and on the right (extreme pain). An increase in score from 0 to 10 indicates a worsening of pain. The number of participants with a decrease of 2 points out of 10 points will be assessed. | Up to Week 4 | 
| Change from Baseline in Quality of Life of Participants and Relatives as Measured by European Quality of Life 5 Dimensions 3-levels (EQ-5D-3L) Questionnaire Score at Week 4 | EQ-5D-3L health questionnaire is a participant/relative answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The status of each dimension had 3 possible responses (1 =no problem, 2 =some problem 3 =severe problems) in the relevant health dimension. Higher score indicated a worsening health condition. The change in quality of life of participants and relatives will be assessed. | Baseline, Week 4 | 
| Percent Change from Baseline in Quality of Life of Participants and Relatives as Measured by EQ-5D-3L Questionnaire Score at Week 4 | EQ-5D-3L health questionnaire is a participant/relative answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The status of each dimension had 3 possible responses (1 =no problem, 2 =some problem 3 =severe problems) in the relevant health dimension. Higher score indicated a worsening health condition. The percent change in quality of life of participants and relatives will be assessed. | Baseline, Week 4 | 
| Number of Participants and Relatives with a Decrease of 2 Points in the EQ-5D-3L VAS Score | The EQ-5D-3L VAS score is a self-assigned rating of overall health using a visual, vertical scale, with a score of 0 as the worst and 100 as the best possible health. The decrease of 2 points in the EQ-5D VAS score represents a worsening in the quality of life for participants and relatives. | Week 4 | 
| Change from Baseline in Quality of Life of Participants as Measured by EQ-5D-3L- Youth Version Questionnaire Score at Week 4 | The EQ-5D-3L-Y contains one question for each of the five dimensions: mobility, looking after myself, doing usual activities, having pain or discomfort, and feeling worried, sad, or unhappy. Participants select from three response levels (no problems, some problems, a lot of problems) for each dimension. A health state profile score can be calculated from the responses on these five questions. The reference to a high score indicates a better outcome of quality of life. | Baseline, Week 4 | 
| Percent Change from Baseline in Quality of Life of Participants as Measured by EQ-5D-3L- Youth Version Questionnaire Score at Week 4 | The EQ-5D-3L-Y contains one question for each of the five dimensions: mobility, looking after myself, doing usual activities, having pain or discomfort, and feeling worried, sad, or unhappy. Participants select from three response levels (no problems, some problems, a lot of problems) for each dimension. A health state profile score can be calculated from the responses on these five questions. The reference to a high score indicates a better outcome of quality of life. | Baseline, Week 4 | 
| Number of Participants with a Decrease of 2 Points in the EQ-5D-Y VAS Score | The EQ-5D-Y VAS score is a self-assigned rating of overall health using a visual, vertical scale, with a score of 0 as the worst and 100 as the best possible health. The decrease of 2 points in the EQ-5D VAS score represents a worsening in the quality of life for participants. | Week 4 | 
| Change from Baseline in Anxiety of Participants and Relatives Using State-Trait Anxiety Inventory (STAI-Y) Scale Scores at Week 4 | The STAI is a commonly used measure of trait and state anxiety. STAI is a psychological inventory based on a 4-point Likert scale and consists of 40 questions on a self-report basis. The STAI measures two types of anxiety - state anxiety or anxiety about an event, and trait anxiety or anxiety level as a personal characteristic. Scores range from 20 to 80, with higher scores correlating with greater anxiety. Each measure has a different rating scale. The 4-point scale for S-anxiety is as follows: 1) not at all, 2) somewhat, 3) moderately so, 4) very much so. The 4-point scale for T-anxiety is as follows: 1) almost never, 2) sometimes, 3.) often, 4) almost always. The change in the anxiety of participants and relatives will be assessed. | Baseline, Week 4 | 
| Percent Change from Baseline in Anxiety of Participants and Relatives Using STAI-Y Scale Scores at Week 4 | The STAI is a commonly used measure of trait and state anxiety. STAI is a psychological inventory based on a 4-point Likert scale and consists of 40 questions on a self-report basis. The STAI measures two types of anxiety - state anxiety or anxiety about an event, and trait anxiety or anxiety level as a personal characteristic. Scores range from 20 to 80, with higher scores correlating with greater anxiety. Each measure has a different rating scale. The 4-point scale for S-anxiety is as follows: 1) not at all, 2) somewhat, 3) moderately so, 4) very much so. The 4-point scale for T-anxiety is as follows: 1) almost never, 2) sometimes, 3.) often, 4) almost always. The percent change in anxiety of participants and relatives will be assessed. | Baseline, Week 4 | 
| Number of Participants and Relatives with a Decrease of at Least one Level of Anxiety State Severity in the State-Trait Anxiety Inventory-State Type (STAI-S) Scale | Severity is defined as a score on STAI-S 20-35 (very low) 36-45 (low) 46-55 (moderate) 56-65 (high) 66-80 (very high). The STAI is a commonly used measure of trait and state anxiety. STAI is a psychological inventory based on a 4-point Likert scale and consists of 40 questions on a self-report basis. The STAI measures two types of anxiety - state anxiety or anxiety about an event, and trait anxiety or anxiety level as a personal characteristic. Scores range from 20 to 80, with higher scores correlating with greater anxiety. The 4-point scale for S-anxiety is as follows: 1) not at all, 2) somewhat, 3) moderately so, 4) very much so. The number of participants and relatives with a decrease of at least one level of anxiety state severity will be assessed. | Week 4 | 
| Change from Baseline in Depression of Participants and Relatives Using Patient Health Questionnaire (Module 9 for Depression) (PHQ-9) Depression Severity Scale Scores at Week 4 | Level of depression severity will be assessed at Week 4 in participants and relatives after inclusion with the PHQ-9 scale. PHQ-9 consists of scores from the nine-item questionnaire ranging from 0 - 27, where 0-5 (none) 5-10 (mild) 10-15 (moderate) 15-20 (moderately severe) 20-27 (severe). Higher scores indicate greater severity of depression. The change in depression of participants and relatives will be assessed. | Baseline, Week 4 | 
| Percent Change from Baseline in Depression of Participants and Relatives Using Patient Health Questionnaire (Module 9 for Depression) (PHQ-9) Depression Severity Scale Scores at Week 4 | Level of depression severity will be assessed at Week 4 in participants and relatives after inclusion with the PHQ-9 scale. PHQ-9 consists of scores from the nine-item questionnaire ranging from 0 - 27, where 0-5 (none) 5-10 (mild) 10-15 (moderate) 15-20 (moderately severe) 20-27 (severe). Higher scores indicate greater severity of depression. The percent change in depression of participants and relatives will be assessed. | Baseline, Week 4 | 
| Number of Participants and Relatives with a Decrease of at Least one level of Depression Severity in the PHQ-9 Scale Scores | Severity is defined as a score on PHQ-9: 0-5 (none) 5-10 (mild) 10-15 (moderate) 15-20 (moderately severe) 20-27 (severe). PHQ-9 consists of scores from the nine-item questionnaire ranging from 0 - 27. Higher scores indicate greater severity of depression. Participants and relatives with a decrease of at least one level of depression severity will be assessed. | Week 4 | 
| Change from Baseline in Adherence to Infusions Using 4-Item Morisky Medication Adherence Scale (MMAS-4) Scores | The Morisky Medication Adherence Scale in the original version (MMAS-4) is a structured self-report measure of medication-taking behavior. It consists of 4 items, with binary scoring (yes/no). Participants score one point for every 'Yes' answer. A score of 0 to 1 indicates low adherence; a score of 2 to 3 indicates medium adherence, and a score of 4 indicates high adherence. The change in adherence to infusions of participants will be assessed. | Baseline, Week 4 | 
| Change from Baseline in Class of Adherence to Infusions Using MMAS-4 Scale at Week 4 | The MMAS-4 is a structured self-report measure of medication-taking behavior. It consists of 4 items, with binary scoring (yes/no). Participants score one point for every 'Yes' answer. A score of 0 to 1 indicates low adherence; a score of 2 to 3 indicates medium adherence, and a score of 4 indicates high adherence. | Baseline, Week 4 | 
| Number of Participants with High Adherence Score (At Score 4) Using MMAS-4 Scale at Week 4 | The Morisky Medication Adherence Scale in the original version (MMAS-4) is a structured self-report measure of medication-taking behavior. It consists of 4 items, with binary scoring (yes/no). Participants score one point for every 'Yes' answer. A score of 0 to 1 indicates low adherence; a score of 2 to 3 indicates medium adherence, and a score of 4 indicates high adherence. Number of participants with score at 4 on the scale will be assessed. | Week 4 | 
| Number of Participants with Low, Medium and High Adherence to Virtual-reality Based Solution Using MMAS-4 Scale at Week 4 | The Morisky Medication Adherence Scale in the original version (MMAS-4) is a structured self-report measure of medication-taking behavior. It consists of 4 items, with binary scoring (yes/no). Participants score one point for every 'Yes' answer. A score of 0 to 1 indicates low adherence; a score of 2 to 3 indicates medium adherence, and a score of 4 indicates high adherence. | Week 4 | 
| Number of Participants, Relatives, and Caregivers with Points 3 or More in Patients' Global Impression of Change (PGIC) Scale at Week 4 | The PGIC is a 7-point Likert scale, a verbal rating scale that asks the respondent to best describe change in symptoms compared to the beginning of study. Participants/relatives/caregivers select from scale range of 1-7: very much improved (1); much improved (2); minimally improved (3); no change (4); minimally worse (5); much worse (6); very much worse (7). Number of participants, relatives, and caregivers with points 3 or more on the scale will be assessed. | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants, Caregivers and Relatives with Satisfaction, Willingness to Continue the Virtual-reality Based Solution Using a 4-point Likert Scale | A 4-point Likert scale was used to assess the number of participants, caregivers, and relatives with a score of 3 or 4 (satisfied or very satisfied) with the use of the virtual-reality-based system. The Likert scale is composed from 1=never satisfied to 4=very satisfied. | Week 4 | 
| Number of Participants, Caregivers and Relatives with Preference for the Virtual-reality Based Solution Using a Binary Question | Preference for the virtual-reality based solution in participants, caregivers and relatives will be assessed using a binary question: Preference for the virtual-reality based solution versus no virtual-reality based solution. | Week 4 | 
| Incidents with the Virtual-reality Based Solution | An incident is a minor hardware and/or software event that prevents the correct use of the solution in its context. The incidents are mainly associated with misuse by the user of the solution or with a software and/or hardware failure. A total number of incidents reported throughout the clinical study will be assessed. | Week 4 | 
| Incidents of Adverse Events (AEs) Related to the Infusions of Factor VIII or Factor IX or Virtual-reality Based Solution, and Serious Adverse Events (SAEs) | An AE is any untoward medical occurrence in a participant administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. AEs related to infusions of Factor VIII or Factor IX or use of virtual-reality based solution will be assessed. An SAE is any untoward medical occurrence that at any dose: results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or any other medically important event that, in the opinion of the healthcare provider, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above. | Up to Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy