Trial to Evaluate the Effectiveness of a Digital Therapeutics in Adults Diagnosed With Major Depressive Disorder (MIRAI)

A Multi-center, Randomized, Controlled Trial to Evaluate the Effectiveness of a Digital Therapeutic (CT-152) as Adjunctive Therapy in Adult Subjects Diagnosed With Major Depressive Disorder

This study compares the effectiveness of 2 digital therapeutics in adult participants diagnosed with major depressive disorder (MDD) who are on antidepressant therapy (ADT) monotherapy for the treatment of depression.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Device: CT-152 - Digital Therapeutic; Device: Sham

Detailed Description

This is a pivotal, 13-week, multi-center, randomized, controlled trial to evaluate the effectiveness and safety of two digital therapeutics in adult participants diagnosed with MDD who are on antidepressant therapy (ADT) monotherapy for the treatment of depression.

The trial consists of a 3-week screening period, a 6-week treatment period, and a 4-week extension. Trial visits will be conducted remotely either by video visit or telephone. The screening visit may be performed in person at the discretion of the investigator. Eligible participants will be randomized to 1 of 2 digital therapeutics within a mobile application that will reside on the participant's personal iPhone or smartphone.

The trial population will include male and female participants between 22 and 64 years of age with a primary diagnosis of major depressive disorder (MDD) who are on an ADT for the treatment of depression. This trial will analyze data gathered from approximately 360 participants in the United States. An interim analysis will be conducted when a targeted sample of the first 180 participants has completed week 6 or discontinued the trial prior to week 6.

• Study Type: Interventional
• Enrollment (Actual): 386
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75231
      • For additional information regarding sites, contact 844-687-8522

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Participants with a current primary diagnosis of MDD.
• Participants with a Hamilton Rating Scale for Depression, 17-item (HAM-D17) score ≥ 18
• Participants who are receiving treatment with an adequate dose and duration of an ADT and who are willing to maintain that same treatment regimen for the duration of this trial.
• Participants who are the only users of an iPhone or an Android smartphone, and agree to download and use the digital mobile application as required by the protocol.

Key Exclusion Criteria:

• Participants with an inadequate response to > 1 adequate trial of ADT for the current episode.
• Participants who are receiving or have received psychotherapy within 90 days prior to screening.
• Participants who are currently using a computer, web, or smartphone software-based application for mental health or depression.
• Participants with a history of schizophrenia, schizoaffective disorder, other psychotic disorder, or Bipolar I/II disorder, or current posttraumatic stress disorder, panic disorder, obsessive-compulsive disorder, or personality disorder
• General Anxiety Disorder/social anxiety can be present as long as they are not the main disorder requiring treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Digital Therapeutic A - CT-152; Participants received digital treatment session by using the CT-152 mobile application (app) from Day 1 up to Week 6 of the treatment period. Each treatment session consisted of Emotional Faces Memory Task (EFMT) exercises and a psychotherapy lesson. From Week 7 up to Week 10 participants continued using the CT-152 app with optional psychotherapy lesson but did not receive any new EFMT exercises during this period. Participants continued receiving brief SMS messages during Weeks 7 to 10 as a reminder of the previously completed CT-152 treatment courses.	Device: CT-152 - Digital Therapeutic; CT-152 mobile app was used by the participants as per the schedule specified in the respective arm.
Other: Digital Therapeutic B - Sham; Participants received digital treatment session by using a sham mobile app from Day 1 up to Week 6 of the treatment period. Each treatment session consisted of a Shape and Memory Task (SMT) exercise only. From Week 7 up to Week 10 participants continued using the sham app but did not receive any new SMT exercises during this period. Participants continued receiving brief SMS messages during Weeks 7 to 10 as a reminder of the previously completed sham treatment courses.	Device: Sham; Sham mobile app was used by the participants as per the schedule specified in the respective arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 6 in the MADRS Total Score	The MADRS is used to assess depressive symptom severity. It consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated from 0 to 6 with zero being the "best" rating and 6 being the "worst" rating. The MADRS total score is the sum of ratings for all 10 items. The total score ranges from 0 to 60. A higher score on the MADRS represents a more severe level of depression. A negative change from baseline indicates improvement. Least square (LS) mean was estimated using Mixed Model Repeated Measures (MMRM) method.	Baseline (Day 1) to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 6 in the GAD-7 Total Score	The GAD-7 is self-reported questionnaire designed to assess anxiety in participants. The scale contains 7 items (anxiety symptoms) and each item was rated by the participants from 0 (not at all) to 3 (nearly every day) based on how much they were bothered by each symptom. The total score ranges from 0 to 21. A higher score on the GAD-7 represents greater anxiety symptomatology. A negative change from baseline indicates improvement. LS mean was estimated using MMRM method.	Baseline (Day 1) to Week 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Weeks 2 and 4 in the MADRS Total Score	The MADRS is used to assess depressive symptom severity. It consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated from 0 to 6 with zero being the "best" rating and 6 being the "worst" rating. The MADRS total score is the sum of ratings for all 10 items. The total score ranges from 0 to 60. A higher score on the MADRS represents a more severe level of depression. A negative change from baseline indicates improvement. LS mean was estimated using MMRM method.	Baseline (Day 1) to Weeks 2 and 4
Change From Baseline to Weeks 2 and 4 in the GAD-7 Total Score	The GAD-7 is self-reported questionnaire designed to assess anxiety in participants. The scale contains 7 items (anxiety symptoms) and each item was rated by the participants from 0 (not at all) to 3 (nearly every day) based on how much they were bothered by each symptom. The total score ranges from 0 to 21. A higher score on the GAD-7 represents greater anxiety symptomatology. A negative change from baseline indicates improvement. LS mean was estimated using MMRM method.	Baseline (Day 1) to Weeks 2 and 4
MADRS Response Rate at Weeks 2, 4, and 6	The MADRS is used to assess depressive symptom severity. It consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated from 0 to 6 with zero being the "best" rating and 6 being the "worst" rating. The MADRS total score is the sum of ratings for all 10 items. The total score ranges from 0 to 60. A higher score on the MADRS represents a more severe level of depression. MADRS Response Rate was defined as the percentage of participants who achieved a reduction in the MADRS total score by 50% or more from baseline.	Baseline (Day 1), Weeks 2, 4 and 6
Change From Baseline to Weeks 2, 4 and 6 in the Clinical Global Impression - Severity of Illness (CGI-S) Score	The CGI-S is a standardized, clinician-administered global rating scale that measures disease severity on a 7-point Likert scale To perform this assessment, the investigator (or designee) answered the following question: "Considering your total clinical experience with this particular population, how mentally ill (as related to agitation) is the participant at this time?" Response choices are 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill subjects. The score 0 (not assessed) will be set to missing. LS mean was estimated using MMRM method.	Baseline (Day 1) to Weeks 2, 4 and 6
Change From Baseline to Week 6 in the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) Total Score	The WHODAS 2.0 is a 36-item self-assessment scale to measure a participant's function and disability across 6 domains of life: cognition (understanding & communicating), mobility (moving & getting around), self-care (hygiene, dressing, eating, staying alone), getting along (interacting with others), life activities (domestic responsibilities, leisure, work & school), & participation (community & society). Each item is rated from 0 (none) to 4 (extreme or cannot do). The total score of the 36 items is converted into a metric ranging from 0 (no-disability) to 100 (full- disability) by dividing the total score by the maximum possible value of the total score, which is 144 for 36 items and multiplying by 100. LS Mean was estimated using ANCOVA method.	Baseline (Day 1) to Week 6
Change From Screening to Weeks 4 and 6 in the PHQ-9 Total Score.	The PHQ-9 is a standardized, self-administered rating scale that assesses the severity of depressive symptoms. The scale consists of 9 items, representing the 9 criteria upon which the diagnosis of DSM-IV depressive disorders is based. Each item is rated from 0 (not at all) to 3 (nearly every day). The total score ranges from 0 to 27. A higher score on the PHQ-9 represents a higher severity of depressive symptoms. LS mean was estimated using MMRM method.	Screening to Weeks 4 and 6
MADRS Partial Response at Weeks 2, 4 and 6	The MADRS is used to assess depressive symptom severity. It consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated from 0 to 6 with zero being the "best" rating and 6 being the "worst" rating. The MADRS total score is the sum of ratings for all 10 items. The total score ranges from 0 to 60. A higher score on the MADRS represents a more severe level of depression. MADRS partial response was defined as the percentage of participants who achieved a reduction in the MADRS total score by 30% or more and less than 50% from baseline.	Baseline (Day 1), Weeks 2, 4 and 6
MADRS Response Rate at Weeks 8 and 10	The MADRS is used to assess depressive symptom severity. It consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated from 0 to 6 with zero being the "best" rating and 6 being the "worst" rating. The MADRS total score is the sum of ratings for all 10 items. The total score ranges from 0 to 60. A higher score on the MADRS represents a more severe level of depression. MADRS Response Rate (full or partial) was defined as the percentage of participants who achieved a reduction in the MADRS total score by 30% or more from baseline.	Baseline (Day 1), Weeks 8 and 10

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Collaborators: Click Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2021
• Primary Completion (Actual): October 26, 2022
• Study Completion (Actual): October 26, 2022

Study Registration Dates

• First Submitted: February 19, 2021
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 25, 2021

Study Record Updates

• Last Update Posted (Actual): October 16, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 345-201-00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
• IPD Sharing Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• IPD Sharing Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes