Clinical trial NCT02431702: 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
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Psychotic Disorders
Keywords: Paliperidone Palmitate
Oral Antipsychotics
Schizophrenia
Psychotic Disorders
Cognition in Schizophrenia
Brain intracortical myelin volume
Personal and Social Performance
Disease Modification
Lead sponsor: Janssen Scientific Affairs, LLC
Sponsor class: INDUSTRY
First posted: 2015-05-01
Enrollment: 337
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Part-2 (Disease Progression): Time to First Treatment Failure
timeFrame: From Day 1 up to 9 Months
measure: Part 3 (Extended Disease Progression [EDP]): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score
timeFrame: Baseline and 18 Months
measure: Part 3 (Disease Modification): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score
timeFrame: Baseline and Day 260
Secondary outcomes:
measure: Part 2 (Disease Progression): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score
timeFrame: Baseline and Month 9
measure: Part 2 (Disease Progression): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score
timeFrame: Baseline and Month 9
measure: 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)
timeFrame: Baseline and Day 260
measure: Part 2 (Disease Progression): Change From Baseline in Working Memory Score: MCCB Domain
timeFrame: Baseline and Day 260
measure: Part 2 (Disease Progression): Change From Baseline in Verbal Learning Score: MCCB Domain
timeFrame: Baseline and Day 260
measure: Part 2 (Disease Progression): Change From Baseline in Speed of Processing Score: MCCB Domain
timeFrame: Baseline and Day 260
measure: Part 2 (Disease Progression): Change From Baseline in Attention/Vigilance Score: MCCB Domain
timeFrame: Baseline and Day 260
measure: Part 2 (Disease Progression): Change From Baseline in Visual Learning Score: MCCB Domain
timeFrame: Baseline and Day 260
measure: Part 2 (Disease Progression): Change From Baseline in Reasoning and Problem Solving: MCCB Domain
timeFrame: Baseline and Day 260
measure: Part 2 (Disease Progression): Change From Baseline in Social Cognition Score: MCCB Domain
timeFrame: Baseline and Day 260
measure: Part 2 (Disease Progression): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score
timeFrame: Baseline, up to 9 Months of Part 2
measure: 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)
timeFrame: Baseline, up to 9 Months
measure: Part 2 (Disease Progression): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Total Score
timeFrame: Baseline and endpoint Part 2 (up to 9 Months)
measure: Part 3 (EDP): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score
timeFrame: Baseline and 18 Months
measure: 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)
timeFrame: Baseline and 18 Months
measure: Part 3 (EDP): Time to First Treatment Failure
timeFrame: From Day 1 Up to 18 Months
measure: Part 3 (EDP): Change From Baseline in Working Memory Score: MCCB Domain
timeFrame: Baseline and 18 Months
measure: Part 3 (EDP): Change From Baseline in Verbal Learning Score: MCCB Domain
timeFrame: Baseline and 18 Months
measure: Part 3 (EDP): Change From Baseline in Speed of Processing Score: MCCB Domain
timeFrame: Baseline and 18 Months
measure: Part 3 (EDP): Change From Baseline in Attention/Vigilance Score: MCCB Domain
timeFrame: Baseline and 18 Months
measure: Part 3 (EDP): Change From Baseline in Visual Learning Score: MCCB Domain
timeFrame: Baseline and 18 Months
measure: Part 3 (EDP): Change From Baseline in Reasoning and Problem Solving: MCCB Domain
timeFrame: Baseline and 18 Months
measure: Part 3 (EDP): Change From Baseline in Social Cognition Score: MCCB Domain
timeFrame: Baseline and 18 Months
measure: Part 3 (EDP): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score
timeFrame: Baseline, up to 18 Months
measure: Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS
timeFrame: Baseline, up to 18 Months
measure: Part 3 (EDP): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Score
timeFrame: Baseline, up to 18 Months
measure: Part 3 (Disease Modification): Personal and Social Performance (PSP) Total Observed Score
timeFrame: Month 9 of Part 3
measure: 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)
timeFrame: Baseline and Month 9 of Part 3
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Garden Grove
country: United States
state: California
city: Lemon Grove
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Rafael
country: United States
state: California
city: Stanford
country: United States
state: California
city: Lauderdale Lakes
country: United States
state: Florida
city: Leesburg
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Granite City
country: United States
state: Illinois
city: Hoffman Estates
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Louisville
country: United States
state: Kentucky
city: Boston
country: United States
state: Massachusetts
city: Worcester
country: United States
state: Massachusetts
city: East Lansing
country: United States
state: Michigan
city: Grand Rapids
country: United States
state: Michigan
city: Muskegon
country: United States
state: Michigan
city: Omaha
country: United States
state: Nebraska
city: Albuquerque
country: United States
state: New Mexico
city: Cedarhurst
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Staten Island
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Eugene
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Bothell
country: United States
state: Washington
city: Itapira
country: Brazil
city: Rio de Janeiro
country: Brazil
city: Sao Jose
country: Brazil
city: Mexico
country: Mexico
Study officials:
affiliation: Janssen Scientific Affairs, LLC
name: Janssen Scientific Affairs, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
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.
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.