A Digital Therapeutic for Treating Major Depressive Disorder: Effectiveness and Safety Results of the MIRAI Randomized Controlled Trial

Abstract: Introduction: Digital therapeutics (DTx) are a new treatment class for major depressive disorder (MDD). This randomized controlled trial evaluated the effectiveness and safety of a novel DTx for MDD as an adjunct to antidepressant treatment (ADT) monotherapy (NCT04770285). Methods: Adults aged 22–64 years with MDD having an inadequate response to current ADT were enrolled in a phase 3 multicenter, randomized, masked, sham-controlled, virtual trial with a 6-week intervention period and 4-week extension. Delivered via smartphone apps, the treatment DTx group received a cognitive-emotional and behavioral intervention whereas the control group received a sham app with a working memory task; all received supportive text messages and continued their current ADT. The primary outcome was Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline to week 6. Treatment-emergent adverse events (TEAEs) were assessed. Results: Of 1034 adults screened, 386 were randomized to the treatment DTx (n=194) or sham (n=192). In the primary efficacy analysis of participants with ≥1 treatment session and ≥1 MADRS assessment post-baseline (n=354), MADRS score changed −9.03 in the treatment DTx group and −7.25 in the sham (difference −1.78, P=.0568). These MADRS results were consistent with data from additional patient and clinician scales. In a sensitivity analysis of the intent-to-treat sample (Nf386), the between-group difference in 6-week MADRS score change from baseline was −2.12 (P=.0211), favoring the treatment DTx. No TEAEs or discontinuations were considered related to the DTx, and no deaths occurred. Conclusions: This treatment DTx resulted in depression symptom improvement with a favorable safety profile.Short Description: This randomized, masked, sham-controlled, virtual trial evaluated the effectiveness and safety of a novel digital therapeutic (DTx) for major depressive disorder as an adjunct to antidepressant treatment monotherapy (NCT04770285). The primary outcome was Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline to week 6 and treatment-emergent adverse events (TEAEs) were assessed. Compared with the sham, the treatment DTx resulted in depression symptom improvement and had a favorable safety profile.Name of Sponsoring Organization(s): This study was funded by Otsuka Pharmaceutical Development & Commercialization, Inc. Click Therapeutics was a co-development collaborator.