Study of Efficacy of PEAR-004 in Schizophrenia

Study Overview
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Brief Summary
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The purpose of the study was to determine in patients currently being administered antipsychotic pharmacotherapy whether PEAR-004 could further reduce symptoms of schizophrenia as measured by the Positive and Negative Syndrome Scale (PANSS). The overall rationale for the study was to assess the first prescription digital therapeutic (PDT) in schizophrenia using a form of proven psychosocial intervention, cognitive behavioral therapy (CBT), to supplement standard of care with antipsychotic medications.

Detailed Description
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This was a randomized, sham-controlled, rater-blinded, parallel group trial. Overall, 112 subjects were randomized 1:1 in to the following groups: Group A: Clinician-directed pharmacotherapy + PEAR-004 Group B: Clinician-directed pharmacotherapy + sham app An up to 28-day screening period included standard screening assessments as defined in the assessment schedule. Eligible subjects were randomized on Day 1 into one of the treatment groups. Subjects in both groups continued to receive their clinician-directed standard-of-care treatment for schizophrenia, including pharmacotherapy. Subjects in Group A used PEAR 004 and subjects in Group B used a sham for a period of 12 weeks. Subjects returned to the clinic for outpatient visits at Week 4 (day 29), Week 8 (day 57), and Week 12 (day 85). At each visit, standard assessments were performed according to the assessment schedule, including PANSS, ISST-Plus, CGI, BMQ, MAP-SR, WHOQOL-BREF, BDI-II, ISI, and adverse events (AEs). A final follow-up visit was performed at Week 16 (day 115),

Official Title
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A Randomized, Sham-Controlled Study of PEAR-004 as an Adjunct to Standard-of-care Treatment for Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Device: PEAR-004
* Device: Sham


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Healthy male and female subjects 18 to 65 years of age, inclusive, and in good health as determined by medical history, physical examination, and vital signs at screening SCID-based DSM-5 diagnosis of schizophrenia and a total PANSS score > 60 Proficient in English at 5th grade reading level or higher, in the judgement of the investigator Capable of using a mobile device (compatible with PEAR-004) and using common applications, in the judgement of the investigator Key Exclusion Criteria: Major change in primary antipsychotic medication in the prior 4 weeks before screening (e.g., switching to a new agent or a dose adjustment within two weeks of randomization) Planning to move out of the geographic area within 3 months Unable to use English to participate in the consent process, the interventions or assessments Inability to comply with study procedures, due to severe medical conditions or otherwise Meet DSM-5 diagnosis for a current episode of major depression, mania, or hypomania in the past month Meet DSM-5 diagnosis for a current moderate or severe alcohol or cannabis use disorder in the past 2 months Meet DSM-5 diagnosis for a current substance use disorder (other than alcohol or cannabis) in the past 2 months Considered high risk for suicidal behavior based on ISST-Plus score at screening, or in the judgement of the investigator Previously participated in a clinical study involving PEAR-004

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEAR-004<br>Eligible participants were able to access PEAR-004 (an investigational digital therapeutic) on a mobile device (iOS and Android based) as needed to receive suggestions about coping strategies to overcome difficulties in daily life. | Device: PEAR-004<br>* PEAR-004 (an investigational digital therapeutic) or sham (control) was downloaded to the subject's phone and then the assigned application was unlocked using a prescription code provided by Pear Therapeutics. As this was a digital therapeutic device study, dose or mode of administration is not applicable.<br>|
| Sham Comparator: Sham<br>Eligible participants were able to access a sham control downloaded on a mobile device (iOS and Android based) as needed to receive notifications prompting the participant to open the sham app, which displayed a prescription timer for the remaining duration of app availability. | Device: Sham<br>* PEAR-004 (an investigational digital therapeutic) or sham (control) was downloaded to the subject's phone and then the assigned application was unlocked using a prescription code provided by Pear Therapeutics. As this was a digital therapeutic device study, dose or mode of administration is not applicable.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) Score | The Positive and Negative Syndrome Scale (PANSS) is a well validated, standardized method of evaluating and monitoring psychotic symptoms. The PANSS assesses: positive (hallucinations, delusions, thought disorder), negative (blunted affect, abstract thinking and general symptomatology. The positive and negative subscale each consist of 7 items rated from 1(absent) - 7(extreme) with a minimum score = 7, maximum score = 49. The general subscale consists of 16 items with a minimum score = 16, maximum score = 112. A Total PANSS score (positive+ negative + general scores) has a minimum of 30 and maximum of 210. Higher scores represent more severity in symptoms. | Baseline, Day 29, Day 57, Day 85 | 
| Percent of Dropout | Dropout rate to evaluate retention to assigned study treatment | Day 115 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Positive PANSS Score | The PANSS includes 3 scales and 30 items: 7 items that make up the Positive Scale (eg, delusions, conceptual disorganization, hallucinatory behavior); 7 items that make up the Negative Scale (eg, blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal); and 16 items that make up the General Psychopathology Scale (eg, somatic concern, anxiety, guilt feelings, mannerisms and posturing, motor retardation, uncooperativeness, disorientation, poor impulse control, preoccupation). Individual items are scored with values ranging from 1 to 7. Total Negative and Positive Subscale scores each range from 7 to 49; higher score indicates greater severity. | Baseline, Day 29, Day 57, Day 85 | 
| Change From Baseline in the General Psychopathology PANSS Score | The PANSS includes 3 scales and 30 items: 7 items that make up the Positive Scale (eg, delusions, conceptual disorganization, hallucinatory behavior); 7 items that make up the Negative Scale (eg, blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal); and 16 items that make up the General Psychopathology Scale (eg, somatic concern, anxiety, guilt feelings, mannerisms and posturing, motor retardation, uncooperativeness, disorientation, poor impulse control, preoccupation). Individual items are scored with values ranging from 1 to 7. Total General Psychopathology Subscale score range from 16 to 112; higher score indicates greater severity. | Baseline, Day 29, Day 57, Day 85 | 
| Change From Baseline in the Negative PANSS Score | The PANSS includes 3 scales and 30 items: 7 items that make up the Positive Scale (eg, delusions, conceptual disorganization, hallucinatory behavior); 7 items that make up the Negative Scale (eg, blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal); and 16 items that make up the General Psychopathology Scale (eg, somatic concern, anxiety, guilt feelings, mannerisms and posturing, motor retardation, uncooperativeness, disorientation, poor impulse control, preoccupation). Individual items are scored with values ranging from 1 to 7. Total Negative and Positive Subscale scores each range from 7 to 49; higher score indicates greater severity. | Baseline, Day 29, Day 57, Day 85 | 
| Change From Baseline in the Motivation and Pleasure Self-report (MAP-SR) Score | The MAP-SR is a 15-item self-report measure that provides a total score index of current motivation/pleasure negative symptoms. Responses are given on a 5-point scale where 0 = no pleasure or motivation and 4 = extreme pleasure or motivation. Total scores range from 0 to 60 and higher scores indicate greater motivation and pleasure during everyday activities. | Baseline, Day 29, Day 57, Day 85 | 
| Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | The WHOQOL-BREF is a 26-item, self-report questionnaire and short version of WHOQOL-100, consisting of 4 domains: physical health (7 items) (Domain 1), psychological health (6 items) (Domian 2), social relationships (3 items) (Domain 3), and environmental health (8 items) (Domain 4); it also contains QOL and general health items. Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life). The mean score of items within each domain is used to calculate the domain score. Each individual item of the WHOQOL-BREF is scored from 1=not at all to 5=completely on a response scale, which is stipulated as a 5-point ordinal scale. The scores are then transformed linearly to a scale of 0 (the worse quality of life) to 100 (the worse quality of life). | Baseline, Day 29, Day 57, Day 85 | 
| Change From Baseline in the Beck Depression Inventory, Second Ed. (BDI-II) Total Score | Beck Depression Inventory (BDI) is a 21-items self reported inventory with a scale evaluating depressive symptoms and the changes in BDI after treatment compared to baseline. The range of scores is 0 to 63, with higher scores indicating greater severity of depression. | Baseline, Day 29, Day 57, Day 85 | 
| Percentage Change From Baseline in Total PANSS Score (Within Assigned Treatment Group) | The Positive and Negative Syndrome Scale (PANSS) is a well validated, standardized method of evaluating and monitoring psychotic symptoms. The PANSS assesses: positive (hallucinations, delusions, thought disorder), negative (blunted affect, abstract thinking and general symptomatology. The positive and negative subscale each consist of 7 items rated from 1(absent) - 7(extreme) with a minimum score = 7, maximum score = 49. The general subscale consists of 16 items with a minimum score = 16, maximum score = 112. A Total PANSS score (positive+ negative + general scores) has a minimum of 30 and maximum of 210. Higher scores represent more severity in symptoms. | Baseline, Day 29, Day 57, Day 85 | 
| Percentage of Responders as Assessed by the Brief Medication Questionnaire (BMQ) | The Brief Medication Questionnaire (BMQ) collects information about current schizophrenia medication use. | Day 29, Day 57, and Day 85 | 
| Percentage of Responders as Assessed by the Total PANSS Score | A Response is defined as a reduction of at least 20% at day 85 or last visit in total PANSS score relative to Baseline. | Day 85 | 
| Number of Patients With Adverse Events | Adverse events, serious adverse events, and adverse events leading to discontinuation throughout the study | Day 115 | 
| Number of Patients With Vital Sign Measurements | Vital signs at baseline, day 85 or last visit | Day 85 | 
| InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score | InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) score. Semi-structured interview to assess severity of suicidal ideation and behavior Part I: collects information on 7 days prior to visit; 13 items scored 0 (min) to 2 (max) for suicidality, with a higher score representing a worse outcome Part II: collects information on suicidal behavior since last visit, with nominal categories Yes / No / Unknown (NA) Part III: global rating of status at time of interview; scored 0 (min) to 5 (max) for suicidality, with a higher score representing a worse outcome. Please note that only part III score (severity of suicidal risk) was summarized and reported. | Baseline, Day 29, 57, 85, and 115 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Digital Therapeutic, CBT, smartphone app, mental disorder, psychosis, acute psychotic reaction, chronic psychosis, failure to recognize what is real, false beliefs, unclear thinking,, confused thinking, auditory hallucinations, paranoia, reduced social engagement, reduced emotional expression