Study of Efficacy of PEAR-004 in Schizophrenia

• ClinicalTrials.gov Identifier: NCT03751280
• Recruitment Status: Completed
• First Posted: November 23, 2018
• Results First Posted: November 23, 2020
• Last Update Posted: January 5, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Schizophrenia	Device: PEAR-004; Device: Sham	Phase 2

Detailed Description:

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),

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Sham-Controlled Study of PEAR-004 as an Adjunct to Standard-of-care Treatment for Schizophrenia
• Actual Study Start Date: December 10, 2018
• Actual Primary Completion Date: September 26, 2019
• Actual Study Completion Date: September 26, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: PEAR-004; 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; 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.
Sham Comparator: Sham; 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; 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.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) Score [ Time Frame: Baseline, Day 29, Day 57, Day 85 ]
   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.
2. Percent of Dropout [ Time Frame: Day 115 ]
   Dropout rate to evaluate retention to assigned study treatment

Secondary Outcome Measures :

1. Change From Baseline in the Positive PANSS Score [ Time Frame: Baseline, Day 29, Day 57, Day 85 ]
   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.
2. Change From Baseline in the General Psychopathology PANSS Score [ Time Frame: Baseline, Day 29, Day 57, Day 85 ]
   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.
3. Change From Baseline in the Negative PANSS Score [ Time Frame: Baseline, Day 29, Day 57, Day 85 ]
   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.
4. Change From Baseline in the Motivation and Pleasure Self-report (MAP-SR) Score [ Time Frame: Baseline, Day 29, Day 57, Day 85 ]
   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.
5. Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale [ Time Frame: Baseline, Day 29, Day 57, Day 85 ]
   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).
6. Change From Baseline in the Beck Depression Inventory, Second Ed. (BDI-II) Total Score [ Time Frame: Baseline, Day 29, Day 57, Day 85 ]
   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.
7. Percentage Change From Baseline in Total PANSS Score (Within Assigned Treatment Group) [ Time Frame: Baseline, Day 29, Day 57, Day 85 ]
   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.
8. Percentage of Responders as Assessed by the Brief Medication Questionnaire (BMQ) [ Time Frame: Day 29, Day 57, and Day 85 ]
   The Brief Medication Questionnaire (BMQ) collects information about current schizophrenia medication use.
9. Percentage of Responders as Assessed by the Total PANSS Score [ Time Frame: Day 85 ]
   A Response is defined as a reduction of at least 20% at day 85 or last visit in total PANSS score relative to Baseline.
10. Number of Patients With Adverse Events [ Time Frame: Day 115 ]
    Adverse events, serious adverse events, and adverse events leading to discontinuation throughout the study
11. Number of Patients With Vital Sign Measurements [ Time Frame: Day 85 ]
    Vital signs at baseline, day 85 or last visit
12. InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score [ Time Frame: Baseline, Day 29, 57, 85, and 115 ]

    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Novartis Investigative Site

Garden Grove, California, United States, 92845

Novartis Investigative Site

Oakland, California, United States, 94607

Novartis Investigative Site

Torrance, California, United States, 90502

United States, Florida

Novartis Investigative Site

Maitland, Florida, United States, 32751

United States, Michigan

Novartis Investigative Site

Grand Rapids, Michigan, United States, 49548

United States, New Mexico

Novartis Investigative Site

Albuquerque, New Mexico, United States, 87102

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):

Statistical Analysis Plan  [PDF] May 15, 2019

Study Protocol  [PDF] October 12, 2018

More Information

Additional Information:

A Plain Language Trial Summary is available on novartisclinicatrials.com 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ghaemi SN, Sverdlov O, van Dam J, Campellone T, Gerwien R. A Smartphone-Based Intervention as an Adjunct to Standard-of-Care Treatment for Schizophrenia: Randomized Controlled Trial. JMIR Form Res. 2022 Mar 28;6(3):e29154. doi: 10.2196/29154.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03751280
• Other Study ID Numbers: CPEA001A12201
• First Posted: November 23, 2018
• Results First Posted: November 23, 2020
• Last Update Posted: January 5, 2021
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• URL: https://www.clinicalstudydatarequest.com/

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

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

Additional relevant MeSH terms:

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders