Digital Therapeutics Reduces Negative Symptoms of Schizophrenia in Phase 3 Trial

Boehringer Ingelheim and Click Therapeutics announced that their phase 3 trial showed their investigational prescription digital therapeutic, used as an adjunct to antipsychotic therapy, significantly reduced experiential negative symptoms in patients with schizophrenia.1 The company presented data at the 38th Annual European College of Neuropsychopharmacology (ECNP) Congress in Amsterdam on October 13, 2025.

“The positive primary endpoint results observed from the CT-155 Phase III trial represent an important step forward in exploring how negative symptoms may be better understood, which is an area of long-standing unmet need in mental health care," said lead investigator Gregory W. Mattingly, MD, associate clinical professor at Washington University in St. Louis.1 “The emergence of prescription digital therapeutics, like CT-155, if approved, may hold the potential for patients to access psychosocial intervention from anywhere."

CT-155, an investigational prescription digital therapeutic, is designed to deliver interactive psychosocial interventions alongside standard antipsychotic therapy for patients with schizophrenia, targeting defeatist beliefs and motivational deficits. It incorporates adaptive goal setting, aligning personalized goals with each patient’s current level of functioning to encourage engagement in real-world activities. The app offers numerous therapeutic interventions, as cognitive restructuring, social skills training, positive affect training, and distress tolerance skills.

“…we developed CT-155 aiming to address the dual challenges of accessibility and consistency of psychosocial therapy use for people living with negative symptoms of schizophrenia,” said Emmanuelle Clerisme-Beaty, senior vice president of medicine at Boehringer Ingelheim Pharmaceuticals, in a statement.1

In CONVOKE, a phase 3, multicenter, randomized, double-blind, 16-week study, investigators assessed the efficacy and safety of CT-155 compared to a digital control app in patients with schizophrenia experiencing negative symptoms.1 Negative symptoms include avolition, asociality, and anhedonia.2 The team enrolled participants aged ≥ 18 years with schizophrenia who were stable on antipsychotic medication.1

The primary endpoint was improvement in experiential negative symptoms from baseline to week 16, measured by changes in the Clinical Assessment for Negative Symptoms, Motivation, and Pleasure Scale (CAINS-MAP). CAINS, a second-generation scale developed under the National Institute of Mental Health and the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS guidance, reflects updated concepts of negative symptoms, with the CAINS-MAP offering detailed assessment of experiential symptoms.

Additional endpoints included change from baseline in CAINS-MAP at week 8, change from baseline in CAINS expressivity scale (CAINS-EXP) at weeks 8 and 16, and changes from baseline in positive symptoms measured by the Positive and Negative Syndrome Scale (PASS) at weeks 8 and 16. Investigators also assessed change from baseline in social functioning measured by the Personal and Social Performance Scale (PSP) at weeks 8 and 16, and the patient global impression of improvement measured by Patient Global Impression of Improvement Scale (PGI-I) at weeks 8 and 16.

The study met its primary endpoint, with a 6-8-point improvement of negative symptoms from baseline to 16 weeks on the CAINS-Map, compared to a 4.2-point improvement in the digital control arm (Cohen’s D effect size, -0.36; P =.0003). Participants on adjunct CT-155 had a 62% relative improvement in negative symptoms.1

Most participants used their assigned app through week 15 (70.4% for CT-155; 76.5% for the control). Engagement was high in both groups. CT-155 users completed activities on 76 of 112 days, and control users on 92 days, indicating CT-155’s benefits are attributable to its unique therapeutic content rather than app design or engagement differences.1

CT-155 was well-tolerated, with adverse events occurring in 8.3% of patients, compared to 13.4% in the digital control arm. No serious adverse events occurred in either arm. No participants in the CT-155 arm discontinued, meanwhile 2 did in the control arm.

“The design and development of CT-155 was informed by an iterative patient-centered approach with more than 150 people living with schizophrenia, ensuring the therapeutic aimed to address the real-life challenges that people with experiential negative symptoms face, such as lack of motivation, social connection, and ability to feel pleasure,” said Austin Speier, Chief Strategy Officer, Click Therapeutics.1 “For decades, negative symptoms have represented one of the greatest unmet needs for people living with schizophrenia, and we are proud to be exploring CT-155 as a potential new treatment modality in mental health.”

References

1. Boehringer. Boehringer and Click Therapeutics present pivotal data for investigational prescription digital therapeutic CT-155 showing a statistically significant reduction in negative symptoms of schizophrenia. Prnewswire.com. Published October 13, 2025. Accessed October 14, 2025. https://www.prnewswire.com/news-releases/boehringer-and-click-therapeutics-present-pivotal-data-for-investigational-prescription-digital-therapeutic-ct-155-showing-a-statistically-significant-reduction-in-negative-symptoms-of-schizophrenia-302582119.html

2. Correll CU, Schooler NR. Negative symptoms in schizophrenia: A review and clinical guide for recognition, assessment, and treatment. Neuropsychiatr Dis Treat. 2020;16:519–534.