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Study of Efficacy of PEAR-004 in Schizophrenia

Primary Purpose

Schizophrenia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PEAR-004
Sham
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring 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

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

PEAR-004

Sham

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
Percent of Dropout
Dropout rate to evaluate retention to assigned study treatment

Secondary Outcome Measures

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.
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.
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.
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.
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).
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.
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.
Percentage of Responders as Assessed by the Brief Medication Questionnaire (BMQ)
The Brief Medication Questionnaire (BMQ) collects information about current schizophrenia medication use.
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.
Number of Patients With Adverse Events
Adverse events, serious adverse events, and adverse events leading to discontinuation throughout the study
Number of Patients With Vital Sign Measurements
Vital signs at baseline, day 85 or last visit
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.

Full Information

First Posted
November 8, 2018
Last Updated
December 9, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03751280
Brief Title
Study of Efficacy of PEAR-004 in Schizophrenia
Official Title
A Randomized, Sham-Controlled Study of PEAR-004 as an Adjunct to Standard-of-care Treatment for Schizophrenia
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
December 10, 2018 (Actual)
Primary Completion Date
September 26, 2019 (Actual)
Study Completion Date
September 26, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

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
Data Monitoring Committee
No

5. 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.
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),

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
112 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PEAR-004
Arm Type
Experimental
Arm Description
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.
Arm Title
Sham
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
PEAR-004
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Sham
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) Score
Description
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.
Time Frame
Baseline, Day 29, Day 57, Day 85
Title
Percent of Dropout
Description
Dropout rate to evaluate retention to assigned study treatment
Time Frame
Day 115
Secondary Outcome Measure Information:
Title
Change From Baseline in the Positive PANSS Score
Description
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.
Time Frame
Baseline, Day 29, Day 57, Day 85
Title
Change From Baseline in the General Psychopathology PANSS Score
Description
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.
Time Frame
Baseline, Day 29, Day 57, Day 85
Title
Change From Baseline in the Negative PANSS Score
Description
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.
Time Frame
Baseline, Day 29, Day 57, Day 85
Title
Change From Baseline in the Motivation and Pleasure Self-report (MAP-SR) Score
Description
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.
Time Frame
Baseline, Day 29, Day 57, Day 85
Title
Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale
Description
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).
Time Frame
Baseline, Day 29, Day 57, Day 85
Title
Change From Baseline in the Beck Depression Inventory, Second Ed. (BDI-II) Total Score
Description
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.
Time Frame
Baseline, Day 29, Day 57, Day 85
Title
Percentage Change From Baseline in Total PANSS Score (Within Assigned Treatment Group)
Description
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.
Time Frame
Baseline, Day 29, Day 57, Day 85
Title
Percentage of Responders as Assessed by the Brief Medication Questionnaire (BMQ)
Description
The Brief Medication Questionnaire (BMQ) collects information about current schizophrenia medication use.
Time Frame
Day 29, Day 57, and Day 85
Title
Percentage of Responders as Assessed by the Total PANSS Score
Description
A Response is defined as a reduction of at least 20% at day 85 or last visit in total PANSS score relative to Baseline.
Time Frame
Day 85
Title
Number of Patients With Adverse Events
Description
Adverse events, serious adverse events, and adverse events leading to discontinuation throughout the study
Time Frame
Day 115
Title
Number of Patients With Vital Sign Measurements
Description
Vital signs at baseline, day 85 or last visit
Time Frame
Day 85
Title
InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score
Description
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.
Time Frame
Baseline, Day 29, 57, 85, and 115

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Garden Grove
State/Province
California
ZIP/Postal Code
92845
Country
United States
Facility Name
Novartis Investigative Site
City
Oakland
State/Province
California
ZIP/Postal Code
94607
Country
United States
Facility Name
Novartis Investigative Site
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
Novartis Investigative Site
City
Maitland
State/Province
Florida
ZIP/Postal Code
32751
Country
United States
Facility Name
Novartis Investigative Site
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49548
Country
United States
Facility Name
Novartis Investigative Site
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87102
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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
IPD Sharing URL
https://www.clinicalstudydatarequest.com/
Citations:
PubMed Identifier
35343910
Citation
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.
Results Reference
derived
Links:
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=554
Description
A Plain Language Trial Summary is available on novartisclinicatrials.com

Learn more about this trial

Study of Efficacy of PEAR-004 in Schizophrenia

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