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A Study to Compare Disease Progression and Modification Following Treatment With Paliperidone Palmitate Long-Acting Injection or Oral Antipsychotics in Participant's With Recent-onset Schizophrenia or Schizophreniform (DREaM)

Primary Purpose

Schizophrenia, Psychotic Disorders

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Aripiprazole

Haloperidol

Olanzapine

Oral Paliperidone ER

Perphenazine

Quetiapine

Oral Risperidone

Paliperidone Palmitate Injection (PP1M)

Paliperidone Palmitate Injection (PP3M)

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring Paliperidone Palmitate, Oral Antipsychotics, Schizophrenia, Psychotic Disorders, Cognition in Schizophrenia, Brain intracortical myelin volume, Personal and Social Performance, Disease Modification

Eligibility Criteria

18 Years - 35 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Participant must have a current diagnosis of schizophrenia (295.90) or schizophreniform disorder (295.40) as defined by Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and confirmed by the Structured Clinical Interview for DSM-5 Disorders (SCID) with a first psychotic episode within the last 24 months prior to the screening visit
Participant requires treatment with an antipsychotic medication
Participant must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study
Participant must have available a designated individual (example, family member, significant other, friend) who has knowledge of the participant and is generally aware of the participants daily activities, and who agrees to let the study site personnel know of changes in the participants circumstances when the participant is not able to provide this information. The designated individual must sign an informed consent form
Participant is anticipated to have a stable place of residence for the duration of the trial

Exclusion Criteria:

Participant has a current DSM-5 diagnosis of dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, autistic disorder, or intellectual disabilities
Participant meets the DSM-5 definition of moderate or severe substance use disorder (except for nicotine) within 2 months prior to Screening
Participant has a history of neuroleptic malignant syndrome
Participant has received long-acting injectable (LAI) medication within 2 injection cycles prior to the Screening visit
Participant has mental retardation, defined as pre-morbid intelligence quotient (IQ) as measured by Wechsler Test of Adult Reading at Screening less than (<) 70

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Arm Label

Part-1: Oral Antipsychotics (OAP)

Part-2: Paliperidone Palmitate (PP)

Part-2: OAP

Part-3: PP - PP

Part-3: OAP - Delayed Start Paliperidone Palmitate (PP)

Part-3: OAP - OAP

Arm Description

All Participants will receive Paliperidone Extended Release (ER) 1.5 to 12 milligram (mg) or risperidone 1 to 6 mg once daily orally for 2 months. Subjects who tolerate paliperidone ER/risperidone but find it inadequately efficacious after treatment for an adequate duration at an adequate dosage (per clinical judgment), may be switched to another protocol-specified OAP at the discretion of the investigator.

Participants who will complete Part-1 will be randomized to receive oral Paliperidone Palmitate (PP) treatment. Participants will receive 5 doses of PP1M (paliperidone palmitate once-monthly injection). First dose at a starting dose of 234 mg on Day 1 and thereafter second dose in second week and then, every month up to Day 92. Participants will be subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M. Participants receiving PP3M may go back to treatment with PP1M (monthly injections of 78, 117, 156 or 234 mg, flexibly dosed) for further dose adjustment or for the duration of the study with the approval of the medical monitor.

Participants who will complete Part-1 will be randomized to receive Oral Antipsychotics for 9 months.

Participants who will complete Part-2 (with PP treatment) will continue to receive Paliperidone Palmitate for 9 months.

Participants who will complete Part-2 (with OAP treatment) will be randomized to receive PP treatment for 9 months. PP treatment includes PP1M and PP3M. Participants will be subsequently switched to PP3M following a minimum of 5 injections of PP1M. Participants receiving PP3M may go back to treatment with PP1M (monthly injections of 78, 117, 156 or 234 mg, flexibly dosed) for further dose adjustment or for the duration of the study with the approval of the medical monitor.

Participants who will complete Part-2 (with OAP treatment) will be randomized to receive OAP treatment for additional 9 months.

Outcomes

Primary Outcome Measures

Part-2 (Disease Progression): Time to First Treatment Failure

Treatment failure is defined as the time from participant's randomization to first treatment failure, which was a composite endpoint consisting of any of the following: 1) Psychiatric hospitalization due to worsening symptoms; 2) Any deliberate self-injury, suicidal ideation or behavior, homicidal ideation or violent behavior that is clinically significant and needs immediate intervention as determined by the study physician; 3) New arrest/incarceration; 4) Discontinuation of antipsychotic treatment due to inadequate efficacy as determined by the study physician; 5) Discontinuation of antipsychotic treatment due to safety or tolerability as determined by the study physician; 6) Treatment supplementation with another antipsychotic due to inadequate efficacy as determined by the study physician; 7) Increase in the level of psychiatric services in order to prevent imminent psychiatric hospitalization as determined by the study physician.

Part 3 (Extended Disease Progression [EDP]): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score

The MATRICS Consensus Cognitive Battery is an instrument that contains 10 tests to measure cognitive performance in 7 cognitive domains: speed processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The composite score combines the individual scores of the 10 tests and scores them on a normative scale to derive a T-score and composites scores. The range of T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Part 3 (Disease Modification): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score

Secondary Outcome Measures

Part 2 (Disease Progression): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score

Part 2 (Disease Progression): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score

The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behavior. Each domain was assessed on a 6-point scale, from 1 (absent) to 6 (very severe) (1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe). PSP total score was calculated as sum of all the domain scores and ranges from 1 to 100. Participants with score of 71 to 100 have mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision. Higher score indicate better performance.

Part 2 (Disease Progression): Change From Baseline in Adjusted Intracortical Myelin (ICM) Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (MRI)

The adjusted ICM fraction score is quantified as: 1. The volume of myelinated brain tissue is measured separately on co-localized IR and proton density (PD) MRI images, by outlining the boundary between gray matter and white matter on each image. 2. ICM is calculated from the difference of "IR volume minus PD volume". 3. ICM is then expressed as a fraction of the total intracranial volume (ICM divided by intracranial volume). 4. The ICM fraction is then adjusted for effects of age, gender, and race/ethnicity in the sample of treated participants and healthy controls. A decrease in the adjusted ICM fraction score may be a sign of disease progression.

Part 2 (Disease Progression): Change From Baseline in Working Memory Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess working memory of participants. The range of working memory score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Part 2 (Disease Progression): Change From Baseline in Verbal Learning Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess verbal learning score of participants. The range of verbal learning score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Part 2 (Disease Progression): Change From Baseline in Speed of Processing Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess speed of processing score of participants. The range of speed of processing T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Part 2 (Disease Progression): Change From Baseline in Attention/Vigilance Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess attention/vigilance score of participants. The range of attention/vigilance score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Part 2 (Disease Progression): Change From Baseline in Visual Learning Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess visual learning score of participants. The range of visual learning score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Part 2 (Disease Progression): Change From Baseline in Reasoning and Problem Solving: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess reasoning and problem solving of participants. The range of reasoning and problem solving T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Part 2 (Disease Progression): Change From Baseline in Social Cognition Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess social cognition score of participants. The range of social cognition score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Part 2 (Disease Progression): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score

The Clinical Global Impression Severity (CGI-S) rating scale is used to rate the severity of a participant's overall clinical condition on a 7 point scale. The score ranges from 1 to 7, where 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Higher scores indicate worsening.

Part 2 (Disease Progression): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by Clinician-Rated Dimensions of Psychosis Symptom Severity Scale (CRDPSS)

The CRDPSS is an 8-item measure that assesses the severity of mental health symptoms that are important across psychotic disorders, including delusions, hallucinations, disorganized speech, abnormal psychomotor behavior, negative symptoms. Each item on the measure is rated on a 5-point scale (0=none; 1=equivocal; 2=present, but mild; 3=present and moderate; and 4=present and severe). Total Score is taken as summation. A higher score indicates a more severe condition. Worsened or improved is defined as increase or decrease compared to baseline.

Part 2 (Disease Progression): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Total Score

The Medication Satisfaction Questionnaire (MSQ) is a 7-point, verbally administered, Likert-type scale rated as follows: 1=Extremely Dissatisfied, 2=Very Dissatisfied, 3=Somewhat Dissatisfied, 4=Neither Satisfied Nor Dissatisfied, 5=Somewhat Satisfied, 6=Very Satisfied, 7=Extremely Satisfied. Worst value is 1 (Extremely Dissatisfied) and best value is 7 (Extremely Satisfied). Total score ranges from 1 to 7. Higher score indicate improvement.

Part 3 (EDP): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score

Part 3 (EDP): Change From Baseline in Adjusted Intracortical Myelin Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (MRI)

Part 3 (EDP): Time to First Treatment Failure

Part 3 (EDP): Change From Baseline in Working Memory Score: MCCB Domain

Part 3 (EDP): Change From Baseline in Verbal Learning Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess verbal learning score of participants. The range of verbal learning score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Part 3 (EDP): Change From Baseline in Speed of Processing Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess speed of processing score of participants. The range of speed of processing score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Part 3 (EDP): Change From Baseline in Attention/Vigilance Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess attention/vigilance score of participants. The range of attention/vigilance score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Part 3 (EDP): Change From Baseline in Visual Learning Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess visual learning score of participants. The range of visual learning score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Part 3 (EDP): Change From Baseline in Reasoning and Problem Solving: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess reasoning and problem solving score of participants. The range of reasoning and problem solving T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Part 3 (EDP): Change From Baseline in Social Cognition Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess social cognition score of participants. The range of social cognition score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Part 3 (EDP): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score

The Clinical Global Impression Severity (CGI-S) rating scale is used to rate the severity of a participant's overall clinical condition on a 7 point scale. The total score ranges from 1 to 7, where 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Higher scores indicate worsening.

Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS

Part 3 (EDP): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Score

Part 3 (Disease Modification): Personal and Social Performance (PSP) Total Observed Score

The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behavior. Score ranges from 1 to 100, divided into 10 equal intervals to rate degree of difficulty (1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe) in each of the 4 domains. Based on 4 domains there will be 1 transformed total score. Participants with score of 71 to 100 have mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision.

Part 3 (Disease Modification): Change From Baseline in Adjusted Intracortical Myelin Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (SE MRI)

Full Information

NCT ID

NCT02431702

First Posted

April 28, 2015

Last Updated

December 2, 2021

Sponsor

Janssen Scientific Affairs, LLC

1. Study Identification

Unique Protocol Identification Number

NCT02431702

Brief Title

A Study to Compare Disease Progression and Modification Following Treatment With Paliperidone Palmitate Long-Acting Injection or Oral Antipsychotics in Participant's With Recent-onset Schizophrenia or Schizophreniform

Acronym

DREaM

Official Title

A Prospective, Matched-Control, Randomized, Open-Label, Flexible-Dose, Study in Subjects With Recent-Onset Schizophrenia or Schizophreniform Disorder to Compare Disease Progression and Disease Modification Following Treatment With Paliperidone Palmitate Long-Acting Injection or Oral Antipsychotics

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Completed

Study Start Date

July 8, 2015 (Actual)

Primary Completion Date

November 12, 2019 (Actual)

Study Completion Date

November 12, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Scientific Affairs, LLC

4. Oversight

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of the study is to compare effectiveness of paliperidone palmitate (PP: paliperidone palmitate once-monthly and 3-month injections) versus oral antipsychotic (OAP [that is oral paliperidone extended release {ER}, oral risperidone, or another OAP]) in delaying time to treatment failure. The study will also evaluate changes in cognition, functioning, brain intracortical myelin (ICM) volume following treatment with PP compared with OAP in participants with recent-onset schizophrenia or schizophreniform disorder.

Detailed Description

A Prospective, matched-control, Randomized (assignment of study drug by chance), open-label, flexible-dose, study in participants with recent-onset schizophrenia or schizophreniform disorder to compare disease progression and disease modification following treatment with PP long-acting injection (once-monthly followed by 3-month injections) or OAP (Any of the following 7 OAPs are permitted: aripiprazole, haloperidol, olanzapine, paliperidone ER, perphenazine, quetiapine, and risperidone). The study consists of 3 parts. Part-1 (Oral Run-In Phase), Part-2 (Disease Progression) and Part-3 (Extended Disease Progression and Disease Modification) with unique endpoints. Screening period will be up to 4 Weeks. Duration of Parts will be as: 2 months for Part-1, 9 months for Part-2 and Part-3. All participants will initially receive oral paliperidone ER or oral risperidone in Part-1. After paliperidone/risperidone treatment in Part-1, participants will be randomized into 1:2 ratio to receive PP or OAP in Part-2. Participants who complete Part-2 will enter into Part-3 wherein OAP group participants of Part-2 will be re-randomized into 1:1 ratio to OAP-OAP group and OAP-PP group, and PP group will continue without further randomization. Treatment failures will be evaluated in Part-2 and Part-3 of the study. Also changes in cognition, functioning, brain intracortical myelin (ICM) volume will be evaluated in the study. Participants' safety will be monitored throughout. Healthy controls (comparable in age, sex, race, and highest parental education to the treated participants) were recruited at each of the 3 MRI centers as controls for the MRI machine calibration for the duration of the study. These healthy controls were to undergo MRI assessments, but were not otherwise involved with the study and did not receive study medication. No safety or efficacy data were collected for these healthy controls.

6. Conditions and Keywords

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

Schizophrenia, Psychotic Disorders

Keywords

Paliperidone Palmitate, Oral Antipsychotics, Schizophrenia, Psychotic Disorders, Cognition in Schizophrenia, Brain intracortical myelin volume, Personal and Social Performance, Disease Modification

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

337 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part-1: Oral Antipsychotics (OAP)

Arm Type

Active Comparator

Arm Description

Arm Title

Part-2: Paliperidone Palmitate (PP)

Arm Type

Experimental

Arm Description

Arm Title

Part-2: OAP

Arm Type

Active Comparator

Arm Description

Participants who will complete Part-1 will be randomized to receive Oral Antipsychotics for 9 months.

Arm Title

Part-3: PP - PP

Arm Type

Experimental

Arm Description

Participants who will complete Part-2 (with PP treatment) will continue to receive Paliperidone Palmitate for 9 months.

Arm Title

Part-3: OAP - Delayed Start Paliperidone Palmitate (PP)

Arm Type

Experimental

Arm Description

Arm Title

Part-3: OAP - OAP

Arm Type

Active Comparator

Arm Description

Participants who will complete Part-2 (with OAP treatment) will be randomized to receive OAP treatment for additional 9 months.

Intervention Type

Drug

Intervention Name(s)

Aripiprazole

Intervention Description

Aripiprazole will be administered in accordance with the label or Investigator's discretion

Intervention Type

Drug

Intervention Name(s)

Haloperidol

Intervention Description

Haloperidol will be administered in accordance with the label or Investigator's discretion

Intervention Type

Drug

Intervention Name(s)

Olanzapine

Intervention Description

Olanzapine will be administered in accordance with the label or Investigator's discretion

Intervention Type

Drug

Intervention Name(s)

Oral Paliperidone ER

Intervention Description

Paliperidone Extended Release (ER) tablets 1.5 to 12 milligram (mg) per day will be administered orally.

Intervention Type

Drug

Intervention Name(s)

Perphenazine

Intervention Description

Perphenazine will be administered in accordance with the label or Investigator's discretion

Intervention Type

Drug

Intervention Name(s)

Quetiapine

Intervention Description

Quetiapine will be administered in accordance with the label or Investigator's discretion

Intervention Type

Drug

Intervention Name(s)

Oral Risperidone

Intervention Description

Risperidone tablets 1-6 mg per day will be administered orally.

Intervention Type

Drug

Intervention Name(s)

Paliperidone Palmitate Injection (PP1M)

Intervention Description

Participants will receive 5 doses of PP1M. First dose at a starting dose of 234 mg on Day 1 and a second dose of 156 mg on Day 8 and then 78 to 234 mg (in 3 flexible doses), every month up to Day 92.

Intervention Type

Drug

Intervention Name(s)

Paliperidone Palmitate Injection (PP3M)

Intervention Description

Paliperidone Palmitate injection (PP3M) will be administered once every 12 weeks intramuscularly. The initial dose will be calculated as 3.5 fold multiple of the final PP1M dose administered on Day 92 (or Day 176). Dose will be increased based on Investigator's discretion.

Primary Outcome Measure Information:

Title

Part-2 (Disease Progression): Time to First Treatment Failure

Description

Time Frame

From Day 1 up to 9 Months

Title

Part 3 (Extended Disease Progression [EDP]): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score

Description

Time Frame

Baseline and 18 Months

Title

Part 3 (Disease Modification): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score

Description

Time Frame

Baseline and Day 260

Secondary Outcome Measure Information:

Title

Part 2 (Disease Progression): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score

Description

Time Frame

Baseline and Month 9

Title

Part 2 (Disease Progression): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score

Description

Time Frame

Baseline and Month 9

Title

Part 2 (Disease Progression): Change From Baseline in Adjusted Intracortical Myelin (ICM) Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (MRI)

Description

Time Frame

Baseline and Day 260

Title

Part 2 (Disease Progression): Change From Baseline in Working Memory Score: MCCB Domain

Description

Time Frame

Baseline and Day 260

Title

Part 2 (Disease Progression): Change From Baseline in Verbal Learning Score: MCCB Domain

Description

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess verbal learning score of participants. The range of verbal learning score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Time Frame

Baseline and Day 260

Title

Part 2 (Disease Progression): Change From Baseline in Speed of Processing Score: MCCB Domain

Description

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess speed of processing score of participants. The range of speed of processing T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Time Frame

Baseline and Day 260

Title

Part 2 (Disease Progression): Change From Baseline in Attention/Vigilance Score: MCCB Domain

Description

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess attention/vigilance score of participants. The range of attention/vigilance score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Time Frame

Baseline and Day 260

Title

Part 2 (Disease Progression): Change From Baseline in Visual Learning Score: MCCB Domain

Description

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess visual learning score of participants. The range of visual learning score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Time Frame

Baseline and Day 260

Title

Part 2 (Disease Progression): Change From Baseline in Reasoning and Problem Solving: MCCB Domain

Description

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess reasoning and problem solving of participants. The range of reasoning and problem solving T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Time Frame

Baseline and Day 260

Title

Part 2 (Disease Progression): Change From Baseline in Social Cognition Score: MCCB Domain

Description

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess social cognition score of participants. The range of social cognition score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Time Frame

Baseline and Day 260

Title

Part 2 (Disease Progression): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score

Description

Time Frame

Baseline, up to 9 Months of Part 2

Title

Description

Time Frame

Baseline, up to 9 Months

Title

Part 2 (Disease Progression): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Total Score

Description

Time Frame

Baseline and endpoint Part 2 (up to 9 Months)

Title

Part 3 (EDP): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score

Description

Time Frame

Baseline and 18 Months

Title

Part 3 (EDP): Change From Baseline in Adjusted Intracortical Myelin Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (MRI)

Description

Time Frame

Baseline and 18 Months

Title

Part 3 (EDP): Time to First Treatment Failure

Description

Time Frame

From Day 1 Up to 18 Months

Title

Part 3 (EDP): Change From Baseline in Working Memory Score: MCCB Domain

Description

Time Frame

Baseline and 18 Months

Title

Part 3 (EDP): Change From Baseline in Verbal Learning Score: MCCB Domain

Description

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess verbal learning score of participants. The range of verbal learning score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Time Frame

Baseline and 18 Months

Title

Part 3 (EDP): Change From Baseline in Speed of Processing Score: MCCB Domain

Description

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess speed of processing score of participants. The range of speed of processing score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Time Frame

Baseline and 18 Months

Title

Part 3 (EDP): Change From Baseline in Attention/Vigilance Score: MCCB Domain

Description

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess attention/vigilance score of participants. The range of attention/vigilance score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Time Frame

Baseline and 18 Months

Title

Part 3 (EDP): Change From Baseline in Visual Learning Score: MCCB Domain

Description

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess visual learning score of participants. The range of visual learning score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Time Frame

Baseline and 18 Months

Title

Part 3 (EDP): Change From Baseline in Reasoning and Problem Solving: MCCB Domain

Description

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess reasoning and problem solving score of participants. The range of reasoning and problem solving T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Time Frame

Baseline and 18 Months

Title

Part 3 (EDP): Change From Baseline in Social Cognition Score: MCCB Domain

Description

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess social cognition score of participants. The range of social cognition score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

Time Frame

Baseline and 18 Months

Title

Part 3 (EDP): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score

Description

Time Frame

Baseline, up to 18 Months

Title

Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS

Description

Time Frame

Baseline, up to 18 Months

Title

Part 3 (EDP): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Score

Description

Time Frame

Baseline, up to 18 Months

Title

Part 3 (Disease Modification): Personal and Social Performance (PSP) Total Observed Score

Description

The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behavior. Score ranges from 1 to 100, divided into 10 equal intervals to rate degree of difficulty (1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe) in each of the 4 domains. Based on 4 domains there will be 1 transformed total score. Participants with score of 71 to 100 have mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision.

Time Frame

Month 9 of Part 3

Title

Part 3 (Disease Modification): Change From Baseline in Adjusted Intracortical Myelin Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (SE MRI)

Description

Time Frame

Baseline and Month 9 of Part 3

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

35 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participant must have a current diagnosis of schizophrenia (295.90) or schizophreniform disorder (295.40) as defined by Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and confirmed by the Structured Clinical Interview for DSM-5 Disorders (SCID) with a first psychotic episode within the last 24 months prior to the screening visit Participant requires treatment with an antipsychotic medication Participant must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study Participant must have available a designated individual (example, family member, significant other, friend) who has knowledge of the participant and is generally aware of the participants daily activities, and who agrees to let the study site personnel know of changes in the participants circumstances when the participant is not able to provide this information. The designated individual must sign an informed consent form Participant is anticipated to have a stable place of residence for the duration of the trial Exclusion Criteria: Participant has a current DSM-5 diagnosis of dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, autistic disorder, or intellectual disabilities Participant meets the DSM-5 definition of moderate or severe substance use disorder (except for nicotine) within 2 months prior to Screening Participant has a history of neuroleptic malignant syndrome Participant has received long-acting injectable (LAI) medication within 2 injection cycles prior to the Screening visit Participant has mental retardation, defined as pre-morbid intelligence quotient (IQ) as measured by Wechsler Test of Adult Reading at Screening less than (<) 70

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Scientific Affairs, LLC Clinical Trial

Organizational Affiliation

Janssen Scientific Affairs, LLC

Official's Role

Study Director

Facility Information:

City

Little Rock

State/Province

Arkansas

Country

United States

City

Garden Grove

State/Province

California

Country

United States

City

Lemon Grove

State/Province

California

Country

United States

City

Los Angeles

State/Province

California

Country

United States

City

San Diego

State/Province

California

Country

United States

City

San Rafael

State/Province

California

Country

United States

City

Stanford

State/Province

California

Country

United States

City

Lauderdale Lakes

State/Province

Florida

Country

United States

City

Leesburg

State/Province

Florida

Country

United States

City

Miami

State/Province

Florida

Country

United States

City

Tampa

State/Province

Florida

Country

United States

City

West Palm Beach

State/Province

Florida

Country

United States

City

Chicago

State/Province

Illinois

Country

United States

City

Granite City

State/Province

Illinois

Country

United States

City

Hoffman Estates

State/Province

Illinois

Country

United States

City

Indianapolis

State/Province

Indiana

Country

United States

City

Louisville

State/Province

Kentucky

Country

United States

City

Boston

State/Province

Massachusetts

Country

United States

City

Worcester

State/Province

Massachusetts

Country

United States

City

East Lansing

State/Province

Michigan

Country

United States

City

Grand Rapids

State/Province

Michigan

Country

United States

City

Muskegon

State/Province

Michigan

Country

United States

City

Omaha

State/Province

Nebraska

Country

United States

City

Albuquerque

State/Province

New Mexico

Country

United States

City

Cedarhurst

State/Province

New York

Country

United States

City

Rochester

State/Province

New York

Country

United States

City

Staten Island

State/Province

New York

Country

United States

City

Charlotte

State/Province

North Carolina

Country

United States

City

Cincinnati

State/Province

Ohio

Country

United States

City

Columbus

State/Province

Ohio

Country

United States

City

Eugene

State/Province

Oregon

Country

United States

City

Philadelphia

State/Province

Pennsylvania

Country

United States

City

Houston

State/Province

Texas

Country

United States

City

Bothell

State/Province

Washington

Country

United States

City

Itapira

Country

Brazil

City

Rio de Janeiro

Country

Brazil

City

Sao Jose

Country

Brazil

City

Mexico

Country

Mexico

12. IPD Sharing Statement

Citations:

PubMed Identifier

35939921

Citation

Alphs L, Baker P, Brown B, Fu DJ, Turkoz I, Nuechterlein KH. Evaluation of major treatment failure in patients with recent-onset schizophrenia or schizophreniform disorder: A post hoc analysis from the Disease Recovery Evaluation and Modification (DREaM) study. Schizophr Res. 2022 Oct;248:58-63. doi: 10.1016/j.schres.2022.07.015. Epub 2022 Aug 6.

Results Reference

derived

PubMed Identifier

35247794

Citation

Alphs L, Brown B, Turkoz I, Baker P, Fu DJ, Nuechterlein KH. The Disease Recovery Evaluation and Modification (DREaM) study: Effectiveness of paliperidone palmitate versus oral antipsychotics in patients with recent-onset schizophrenia or schizophreniform disorder. Schizophr Res. 2022 May;243:86-97. doi: 10.1016/j.schres.2022.02.019. Epub 2022 Mar 2.

Results Reference

derived

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