Efficacy and safety of SAT-014, a digital therapeutic for stress-related disorders: a pivotal randomized controlled trial
J.P. Hong1, J.-h. Seo2, S. Lee3, S.Y. Yoo4,5, J.I. Kang6, J. Hahm7, M.K. Bae8, S.E. Choi9
1Sungkyunkwan University School of Medicine, Department of Psychiatry, Seoul, Korea, Republic of, 2Yonsei University Wonju College of Medicine, Department of Psychiatry, Wonju-si, Korea, Republic of, 3Kyung Hee University College of Medicine, Department of Psychiatry, Seoul, Korea, Republic of, 4Seoul National University College of Medicine, Department of Psychiatry, Seoul, Korea, Republic of, 5Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Department of Psychiatry, Seoul, Korea, Republic of, 6Yonsei University College of Medicine, Department of Psychiatry, Seoul, Korea, Republic of, 7S-Alpha Therapeutics, Inc., AI-Data Unit, Seoul, Korea, Republic of, 8S-Alpha Therapeutics, Inc., Medical Unit, Seoul, Korea, Republic of, 9S-Alpha Therapeutics, Inc., R&D, Seoul, Korea, Republic of
Background: The increasing global prevalence of stress-related disorders such as Post-Traumatic Stress Disorder (PTSD) and adjustment disorder (AD) highlights the need for new and more effective therapeutic approaches, with Software as a Medical Device (SaMD) emerging as a potential alternative.
Aims & Objectives: SAT-014 (manufactured by S-Alpha Therapeutics, Inc.) is a SaMD designed to alleviate symptoms of stress-related disorders by translating several elements of Eye Movement Desensitization and Reprocessing (EMDR) and the mindfulness-based cognitive therapy (MBCT) into a digital therapeutic program. The aim of this study is to evaluate the efficacy and safety of SAT-014.
Method: This randomized, open-label, parallel-group pivotal trial enrolled 110 subjects with mild to moderate PTSD or AD and randomly assigned to a test group (SAT-014 plus treatment as usual (TAU)) or a control group (TAU alone). The primary endpoint was the change from baseline in the PTSD Checklist for DSM-5 (PCL-5) score at Week 6.
The secondary efficacy endpoints included changes from baseline in PCL-5 at Weeks 2 and 4, as well as Impact of Event Scale-Revised (IES-R), Beck Anxiety Inventory (BAI), Patient Health Questionnaire-9 (PHQ-9), Hamilton Rating Scale for Anxiety (HAM-A), CGI-S, Clinical Global Impression-Improvement (CGI-I), and Short Form-12 Health Survey (SF-12) at Week 2, 4, and 6. In addition, the response rate, defined as a reduction of 10 or more points in PCL-5 score from baseline, was evaluated.
Safety was assessed by monitoring treatment emergent adverse event (TEAE) and Serious Adverse Events (SAEs). Group differences in the primary and secondary endpoints were analyzed using Analysis of Covariance (ANCOVA), adjusted for baseline scores and stratification factors (target condition and study site).
The secondary efficacy endpoints included changes from baseline in PCL-5 at Weeks 2 and 4, as well as Impact of Event Scale-Revised (IES-R), Beck Anxiety Inventory (BAI), Patient Health Questionnaire-9 (PHQ-9), Hamilton Rating Scale for Anxiety (HAM-A), CGI-S, Clinical Global Impression-Improvement (CGI-I), and Short Form-12 Health Survey (SF-12) at Week 2, 4, and 6. In addition, the response rate, defined as a reduction of 10 or more points in PCL-5 score from baseline, was evaluated.
Safety was assessed by monitoring treatment emergent adverse event (TEAE) and Serious Adverse Events (SAEs). Group differences in the primary and secondary endpoints were analyzed using Analysis of Covariance (ANCOVA), adjusted for baseline scores and stratification factors (target condition and study site).
Results: Of the 110 randomized subjects, 109 were included in the safety set (55 test, 54 control). Among the six TEAEs reported, only one event in the test group was considered device-related, and all reported events were resolved.
The full analysis set included 107 subjects (54 test, 53 control) for the efficacy analysis. Regarding the primary efficacy endpoint, the test group showed significantly greater reduction in PCL-5 score at Week 6 compared with the control group (P=0.04998). Secondary efficacy endpoints demonstrated significant improvements in several measures: PCL-5 score at Week 4 (P=0.0051); IES-R at Week 4 (P=0.0117) and at Week 6 (P=0.0094); HAM-A at Week 2 (P=0.0024), Week 4 (P=0.0228), and Week 6 (P=0.0114); CGI-S at Week 4 (P=0.0205); and CGI-I at Week 2 and Week 6 (P=0.0003 for both).
Other measures, including BAI, PHQ-9, and SF-12, showed a trend toward greater improvement in the test group compared with the control group, although the differences did not reach statistical significance. The test group showed a significantly higher response rate than the control group, with an odds ratio of 2.82 (95% CI: 1.25–6.32; P=0.0122). A high adherence rate to SAT-014 was observed.
The full analysis set included 107 subjects (54 test, 53 control) for the efficacy analysis. Regarding the primary efficacy endpoint, the test group showed significantly greater reduction in PCL-5 score at Week 6 compared with the control group (P=0.04998). Secondary efficacy endpoints demonstrated significant improvements in several measures: PCL-5 score at Week 4 (P=0.0051); IES-R at Week 4 (P=0.0117) and at Week 6 (P=0.0094); HAM-A at Week 2 (P=0.0024), Week 4 (P=0.0228), and Week 6 (P=0.0114); CGI-S at Week 4 (P=0.0205); and CGI-I at Week 2 and Week 6 (P=0.0003 for both).
Other measures, including BAI, PHQ-9, and SF-12, showed a trend toward greater improvement in the test group compared with the control group, although the differences did not reach statistical significance. The test group showed a significantly higher response rate than the control group, with an odds ratio of 2.82 (95% CI: 1.25–6.32; P=0.0122). A high adherence rate to SAT-014 was observed.
Discussion & Conclusions: These findings suggest that SAT-014 may improves symptoms in patients with stress-related disorders. The significantly higher clinical response rate, along with its favorable safety profile and high adherence rate, supports the potential of SAT-014 as a promising therapeutic option.
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