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

Takeda24 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

SUPPORTIVE_CARE

Masking

NONE

Enrollment

Conditions

Hemophilia

Interventions

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).

Eligibility

Sex: MALEMin age: 6 Years

Medical Language ↔ Plain English

Inclusion criteria: 1. Male participant over the age of 6 years, with diagnosed Congenital Hemophilia A or B, whatever the severity is 2. Participant under long-term prophylaxis with intravenous Factor VIII or Factor IX infusions 3. 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 4. Participant affiliated to the national social security or beneficiary to such insurance Exclusion criteria: 1. Participant with known or suspected hypersensitivity to virtual-reality based tools 2. Participant with central venous line for the administration of Factor VIII or Factor IX 3. Participant (and the legal guardians if participant age \<18 years) with history of unreliability or non-cooperation (including for completion of self-reported questionnaires) 4. Participant (and the legal guardians if participant age \<18 years) with insufficient comprehension of French language 5. Participant taking part in another clinical trial 6. 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.

Locations (6)

Centre de Reference Hemophilie Unite D'Hemostase Clinique

Bron, Auvergne-Rhône-Alpes, France

CHU Estaing

Clermont-Ferrand, Auvergne-Rhône-Alpes, France

Hôpital de Hautepierre - Pôle MIRMED

Strasbourg, Grand Est, France

CHU Purpan

Toulouse, Haute-Garonne, France

CHU Pellegrin

Bordeaux, New Aquitaine, France

Hôpital Hôtel-Dieu

Nantes, Pays de la Loire Region, France

Outcomes

Primary Outcomes

Mean Absolute Values of Anxiety Measured by an Anxiety Visual Analogue Scale (A-VAS) Before Each Factor VIII or Factor IX Infusion in Participants and Caregivers

The anxiety of participants and caregivers before each Factor VIII or Factor IX infusion was measured with a 10-points VAS. The A-VAS is a 10-centimeter (cm) line with anchor statements on the left (0:no anxiety) and on the right (10: extreme anxiety). An increase in score from 0 to 10 indicated a worsening of anxiety.

Time frame: At Week 4

Number of Participants With Relative Variation in Anxiety Measured by an Anxiety Visual Analogue Scale (A-VAS) Before and After Each Factor VIII or Factor IX Infusion

The anxiety of participants and caregivers before each Factor VIII or Factor IX infusion was measured with a 10-points VAS. The A-VAS is a 10 cm line with anchor statements on the left (0:no anxiety) and on the right (10: extreme anxiety). An increase in score from 0 to 10 indicated a worsening of anxiety. Participants are categorized based on their A-VAS score values at both Baseline (-5, -3, 0, and 9.1) and Week 4 (-5, -2.3, -1, 0 and 2). The A-VAS score reported within each category represent the mean difference between the score collected after and before infusion (after minus before). A negative value indicates an improvement in anxiety compared to the baseline score, while a positive value indicates a worsening of anxiety compared to the baseline score.

Time frame: Baseline up to Week 4

Number of Participants With Decrease of 2 Points Out of 10 Points in the A-VAS Scale Before Each Factor VIII or Factor IX Infusion

Time frame: At Week 4

Mean Absolute Values of the Pain Measured by a Pain Visual Analogue Scale (P-VAS) After Each Factor VIII or Factor IX Infusion in Participants

Time frame: At Week 4

Number of Participants With Absolute Variation of the Pain Measured by a P-VAS Scale After Each Factor VIII or Factor IX Infusion

The pain of participants after each Factor VIII or Factor IX infusion was measured with a 10-points VAS. The P-VAS is a 10 cm line with anchor statements on the left (0: no pain) and on the right (10: extreme pain). An increase in score from 0 to 10 indicated a worsening of pain. Participants are categorized based on P-VAS score values at both Baseline (0, 1.3, 2, 4 and 5) and Week 4 (0, 0.2, 0.4, 5 and 8). A positive value indicates worsening in pain compared to the baseline score.

Time frame: Baseline up to Week 4

Number of Participants With a Decrease of 2 Points Out of 10 Points in the P-VAS Scale After Each Factor VIII or Factor IX Infusion

Time frame: Baseline up to Week 4

Mean Absolute Values of Anxiety Measured by an A-VAS Scale After Each Factor VIII or Factor IX Infusion in Participants and Caregivers

Time frame: At Week 4

Number of Participants With a Decrease of 2 Points Out of 10 Points in the A-VAS Scale After Each Factor VIII or Factor IX Infusion

Time frame: Baseline up to Week 4

Absolute Variation of Caregivers and Adult Participants Quality of Life Measured With the European Quality of Life 5 Dimensions 3-Levels (EQ-5D-3L) Health State Index Score

The EQ-5D-3L is a standardized instrument for use as a measure of health outcome and was administered to adult participants to assess the effect of the treatment on the participants' quality of life. Adult participants selected answer for each of the following 3-level dimensions: 1) mobility; 2) self-care; 3) usual activities; 4) pain/discomfort; 5) anxiety/depression used to compute an index score ranging from 0 (worst imaginable health state) to 1 (best imaginable health state). An increase in the EQ-5D-3L index score indicated improvement and negative value indicated worst health.

Time frame: At Week 4

Relative Variation of Caregivers and Adult Participants Quality of Life Measured With the European Quality of Life 5 Dimensions 3-Levels (EQ-5D-3L) Health State Index Score

Time frame: At Week 4

Absolute Variation of Youth Participants Quality of Life Measured With the European Quality of Life 5 Dimensions For Youth (EQ-5D-Y) Health State Index Score

The EQ-5D-Y is a standardized instrument for use as a measure of health outcome and was administered to youth participants to assess the effect of the treatment on the participants' quality of life. Youth participants selected answer for each of the following 3-level dimensions: 1) mobility; 2) self-care; 3) usual activities; 4) pain/discomfort; 5) anxiety/depression used to compute an index score ranging from 0 (worst imaginable health state) to 1 (best imaginable health state). An increase in the EQ-5D-Y index score indicated improvement and negative value indicated worst health.

Time frame: At Week 4

Relative Variation of Youth Participants Quality of Life Measured With the European Quality of Life 5 Dimensions For Youth (EQ-5D-Y) Health State Index Score

Time frame: At Week 4

Number of Participants and Caregivers With a Decrease of 2 Points in the EQ-5D-3L VAS and EQ-5D-Y Score

EQ-5D-3L health questionnaire is adult participant and caregivers and EQ-5D-Y is a youth participant 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 =extreme problems) in the relevant health dimension. Higher score indicated a worsening health condition.

Time frame: At Week 4

Absolute Variation of All Participants Anxiety Measured by State-Trait Anxiety Inventory (STAI-Y) Score

The STAI is a psychological inventory consisting of 40 self-report items on a 4-point Likert scale. The STAI measures two types of anxiety - state anxiety (STAI-Y1) and trait anxiety (STAI-Y2). Higher scores were positively correlated with higher levels of anxiety. Each type of anxiety has its own scale of 20 different questions and were rated on a 4-point scale (e.g. from 'Almost Never to 'Almost Always'). Low scores indicated a mild form of anxiety, and high scores indicated a severe form of anxiety. STAI score ranged from 20 to 80 where higher scores indicated greater anxiety and negative value indicated worst anxiety.

Time frame: At Week 4

Relative Variation of All Participants Anxiety Measured by State-Trait Anxiety Inventory (STAI-Y) Score

Time frame: At Week 4

Number of All Participants With Decrease of at Least One Level of State-Trait Anxiety Inventory Severity (STAI-S)

The STAI-S is a psychological assessment tool used to measure the level of anxiety a person is experiencing at a particular moment in time that assesses both State anxiety (STAI-Y1) and Trait anxiety (STAI-Y2). Each type of anxiety has its own scale of 20 different questions each that are scored on a 4-point scale evaluating how respondents feel "right now, at this moment" (e.g. from 'Almost Never to 'Almost Always'). Total scores for each (Y1 and Y2) range from 20 to 80, with higher scores correlating with greater anxiety. Severity for each STAI-Y1 and STAI-Y2 is defined by the scores on STAI-S: 20-35 (very low) 36-45 (low) 46-55 (moderate) 56-65 (high) 66-80 (very high). Number of participants with decrease of at least one level of State-Trait Anxiety Inventory- Severity (STAI-S) are reported.

Time frame: At Week 4

Absolute Variation of Participants Depression Measured by Patient Health Questionnaire (Module 9) (PHQ-9) Depression Severity

The PHQ-9 measures self-reports of depressive symptoms within the prior 2 weeks and has been well-validated, shown high test-retest reliability, shown high internal consistency, and shown to be responsive to changes in treatment. Response options were on a 4-point scale (0 = not at all, 3 = nearly every day). The overall PHQ-9 score ranged from 0 to 27 where 0-5 (none) 5-10 (mild) 10-15 (moderate) 15-20 (moderately severe) 20-27 (severe). Higher values represented more severe depression status.

Time frame: At Week 4

Relative Variation of Participants Depression Measured by Patient Health Questionnaire (Module 9) (PHQ-9) Depression Severity

Time frame: At Week 4

Number of Participants With Decrease of at Least One Level of Depression Severity Measured by PHQ-9 Scale

Time frame: Baseline up to Week 4

Number of Participants With Absolute Adherence to Infusions Measured by 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 behaviour. It consisted of 4 items, with binary scoring (yes/no). Participants scored one point for every 'Yes' answer. A score of 0 to 1 indicated low adherence; a score of 2 to 3 indicated medium adherence, and a score of 4 indicated high adherence.

Time frame: Baseline up to Week 4

Number of Participants With Changes in Adherence to Infusions Measured by MMAS-4 by Classes

Time frame: Baseline up to Week 4

Number of Participants Who Scored 4 (High Adherence) 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 consisted of 4 items, with binary scoring (yes/no). Participants scored one point for every 'Yes' answer. A score of 0 to 1 indicated low adherence; a score of 2 to 3 indicated medium adherence, and a score of 4 indicated high adherence.

Time frame: At Week 4

Number of Participants and Caregivers With Adherence to VR-Based Solutions at Week 4

Adherence to the VR-based solution was assessed at Week 4 using the MMAS. The Morisky Medication Adherence Scale in the original version (MMAS-4) is a structured self-report measure of medication-taking behaviour. It consisted of 4 items, with binary scoring (yes/no). Participants scored one point for every 'Yes' answer. A score of 0 to 1 indicated low adherence; a score of 2 to 3 indicated medium adherence, and a score of 4 indicated high adherence.

Time frame: At Week 4

Number of Participants With a Patients' Global Impression of Change (PGIC) Score Greater Than (>) 3 Among Participants and Caregivers

The PGIC is a 7-point Likert scale, a verbal rating scale that asked the respondent to best describe change in symptoms compared to the beginning of study. Participants/caregivers selected from scale range of 1 (very much worsened) to 7 (very much improved). Higher score indicated improved outcome.

Time frame: At Week 4

Secondary Outcomes

Number of Participants, With Satisfaction, Willingness to Continue the VR-Based Solution Measured by 4-point Likert Scale Score More Than and Equal to (>=3) Among Participants and Caregivers

A 4-point Likert scale was used to assess the number of participants, caregivers, and investigators with a score of 3 or 4 (satisfied or very satisfied) with the use of the VR- based system. The Likert scale is composed from 1=never satisfied to 4=very satisfied.

Time frame: At Week 4

Number of Participants With Preference and No-preference for the VR-Based Solution Using a Binary Question Among Participants and Caregivers

Preference for the VR-based solution in participants and caregivers was assessed using a binary question: Yes (Preference for the VR-based solution) and No (preference for VR-based solution) was assessed.

Time frame: At Week 4

Number of Incidents With the VR-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 were mainly associated with misuse by the user of the solution or with a software and/or hardware failure.

Time frame: Baseline up to Week 4

Number of Participants With Related Adverse Events (AEs) and Serious Adverse Events (SAEs) to the Infusions of Factor VIII or Factor IX or VR-Based Solution

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 VR-based solution was 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.

Time frame: From start of study up to Week 4