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

NCT05437211 | Completed Results DMC

• 2 other identifiers: TAK-660-4013MACS-2020-120101
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Hemophilia

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (24)

• 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.

  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.

  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

  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.

  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

  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.

  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.

  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

  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.

  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

  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.

  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

  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 and negative value indicated worst health.

  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.

  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

  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. Relative variation from baseline at visit (%) = 100 \* Absolute change from baseline at visit (in units) / value at baseline (in units).

  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.

  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

  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. Relative variation from baseline at visit (%) = 100 \* Absolute change from baseline at visit (in units) / value at baseline (in units).

  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.

  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.

  At Week 4

• Relative 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. Relative variation from baseline at visit (%) = 100 \* Absolute change from baseline at visit (in units) / value at baseline (in units).

  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.

  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.

  At Week 4

• Relative 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. Relative variation from baseline at visit (%) = 100 \* Absolute change from baseline at visit (in units) / value at baseline (in units).

  At Week 4

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

  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.

  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.

  Baseline up to Week 4

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

  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.

  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.

  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.

  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.

  At Week 4

Secondary Outcomes (4)

• 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

  At Week 4

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

  At Week 4

• Number of Incidents With the VR-Based Solution

  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

  From start of study up to Week 4

Study Arms (1)

VR-based Experimental Group

EXPERIMENTAL

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

Interventions

Virtual-reality (VR) Based Solution DEVICE

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).

VR-based Experimental Group

Eligibility Criteria

• Age: 6 Years+
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (6)

Centre de Reference Hemophilie Unite D'Hemostase Clinique

Bron, Auvergne-Rhône-Alpes, 69677, France

Location

CHU Estaing

Clermont-Ferrand, Auvergne-Rhône-Alpes, 69003, France

Location

Hôpital de Hautepierre - Pôle MIRMED

Strasbourg, Grand Est, 7200, France

Location

CHU Purpan

Toulouse, Haute-Garonne, 31059, France

Location

CHU Pellegrin

Bordeaux, Nouvelle-Aquitaine, 33076, France

Location

Hôpital Hôtel-Dieu

Nantes, Pays de la Loire Region, 4093, France

Location

Related Links

• To obtain more information on the study, click here/on this link.

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2022
• First Posted: June 29, 2022
• Study Start: June 23, 2023
• Primary Completion: February 21, 2024
• Study Completion: February 21, 2024
• Last Updated: June 5, 2025
• Results First Posted: June 5, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

FR (6)