Recruiting
Phase 3

Roluperidone

Sponsor:

Minerva Neurosciences

Code:

NCT07565428

Conditions

Negative Symptoms of Schizophrenia

Eligibility Criteria

Sex: All

Age: 18 - 55

Healthy Volunteers: Not accepted

Interventions

Roluperidone

risperidone

aripiprazole

olanzapine

Placebo

Study Details

Brief summary:

Evaluate the efficacy, as well as safety and pharmacokinetics, of Roluperidone in improving the negative symptoms of schizophrenia in adult subjects in Phase A of study, followed by Phase B of study to evaluate the relapse rate of Roluperidone and antipsychotic medications.

Conditions

Negative Symptoms of Schizophrenia

Study ID

NCT07565428

Start date

Apr 23, 2026

Status verified date

Jul, 2026

Completion date

Dec, 2028

Anticipated

Primary completion date

Dec, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 55

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Subject and subject's legal representative, if applicable, provided informed consent prior to the initiation of any study related procedures, and the subject is judged by the investigator as being capable of understanding the study requirements.
  • Male or female, 18 to 55 years of age, inclusive, and body mass index (BMI) </= 35.0 kg/m2 at Screening.
  • Meets the diagnostic criteria for schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5), as established by a full psychiatric interview in conjunction with the Mini International Neuropsychiatric Interview (MINI).
  • Has a caregiver or family member or health care personnel (as permitted by local regulations) who can provide information towards assessment and support the subject in terms of compliance with the protocol. The caregiver must have contact with the subject frequently and is not expected to change during the trial.
  • Documented diagnosis of schizophrenia for at least 1 year before screening into the trial.
  • Is stable in terms of both positive and negative symptoms of schizophrenia over the last 6 months according to his or her clinician and/or based on documentation in the clinical chart or medical records, and/or based on information from a professional caregiver (where permitted by local regulations) when formal clinician documentation is not available. Subjects with or without positive symptoms are allowed if these symptoms are stable for the last 6 months and the subjects do not meet exclusion criterion 2.
  • Is currently an outpatient and has not been hospitalized for the last 6 months for acute exacerbation or symptoms worsening.
  • Has had a stable living condition (residence) for the last 6 months.
  • Has not been hospitalized within 6 months before Screening. A subject hospitalized for any time period during the last 6 months for social reasons or currently hospitalized for reasons not related to their schizophrenia illness (e.g., has no support system in the community or needs to have eligibility for disability support periodically re-assessed) can be included only with sponsor/CRO's medical monitors approval and after considering the applicable local regulation requirements. The social reasons for admission or residing in a hospital must be documented in the source documents and the electronic case report form (eCRF).
  • Has a score of > 20 on the PANSS negative subscale score (\[sum of N1+N2+N3+N4+N5+N6+N7\]) at Screening (Visit 1) and Baseline (Visit 3) AND < 4 points absolute difference between Visits 1 and 3.
  • Must discontinue any psychotropic medications by or at the beginning of the washout phase (Day -2). The rate of washout/discontinuation of psychotropic medications during the Screening period should be gradual in order to reduce the risk of psychotropic withdrawal symptoms but remains at the discretion of the investigator.
  • Has no history of violence against self or others.
  • Female subject, if not of childbearing potential, defined as a woman who is post-menopausal or permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy).
  • Female subject, if of childbearing potential, must test negative for pregnancy and must use 2 approved methods of highly effective contraception.
  • Must be normal or ultrarapid metabolizer for cytochrome P450 (CYP) 2D6, defined as having an activity score (AS) of >/= 1.25 as determined by study-specific genotyping test before the first dose of study drug dose is administered.
  • Subject and the caregiver are considered by the investigator to be reliable and likely to cooperate with the assessment procedures.

Exclusion Criteria:

  • Current major depressive disorder, bipolar disorder, panic disorder, obsessive compulsive disorder, or intellectual disability (intellectual developmental disorder diagnosed by age 14), drugs or alcohol addiction.
  • PANSS item score of > 4 on any of the following items: P4 Excitement/Hyperactivity; P6 Suspiciousness/persecution; P7 Hostility; G8 Uncooperativeness; G14 Poor impulse control.
  • A Calgary Depression Scale for Schizophrenia (CDSS) total score > 6.
  • A score of >/= 2 on any 2 items of items 1, 2, or 3, or a score of >/= 3 on item 4 of the Barnes Akathisia Rating Scale (BARS).
  • Subject's condition is due to direct physiological effects of a substance (e.g., a drug of abuse, or medication) or a general medical condition.
  • Current or recent history of serious suicidal behavior within the past 1 year.
  • History of substance use disorder within 3 months of the Screening visit (excluding caffeine and cigarette smoking).
  • Positive urine drug screen for any drug of abuse (cocaine, methadone, amphetamines, cannabinoids, opiates, benzodiazepines, and barbiturates), tricyclic antidepressants (TCA), and alcohol (except for prescription benzodiazepines).
  • Cannot be discontinued from psychotropics.
  • Received clozapine within 6 months of the Screening visit except when used for insomnia at doses </= 100 mg per day.
  • Was treated with electroconvulsive therapy or transcranial magnetic stimulation in the last 12 months.
  • Is receiving treatment with long-acting or depot antipsychotic medication unless the drug has been discontinued for a full cycle drug (1 months, 3 months, 6 months depending on the drug formulation) to allow for sufficient washout before receiving the study drug.
  • History of significant renal disorder, including an eGFR < 60 mL/min at the Screening visit.
  • History of significant other major or unstable neurological, neurosurgical (e.g., head trauma), metabolic, hepatic, hematological, pulmonary, cardiovascular, metabolic, gastrointestinal, urological disorder, or symptomatic orthostatic hypotension.
  • History of seizures (subjects with a history of a single childhood febrile seizure may be enrolled in this study).
  • Clinically significant abnormalities in hematology, blood chemistry (including ALT or AST > 3 × the upper limit of normal \[ULN\], total bilirubin > 2 × ULN, or alkaline phosphatase > 1.5 × ULN), or physical examination not resolved by the Baseline visit which according to Investigator can interfere with study participation.
  • Safety laboratory results from the Pretreatment Phase show one or more of the following: potassium < 3.4 mmol/L, calcium < 2.07 mmol/L, or magnesium < 0.70 mmol/L.
  • Current systemic infection (e.g., Hepatitis B, Hepatitis C, human immunodeficiency virus \[HIV\], tuberculosis). A subject with positive Hepatitis B core antibody test and negative Hepatitis B Surface Antigen (HBsAg) may be included in the study if aminotransferase levels (alanine aminotransferase/ serum glutamate pyruvate transaminase \[ALT/SGPT\] and aspartate aminotransferase/ serum glutamic oxaloacetic transaminase \[AST/SGOT\]) do not exceed 2 × ULN.
  • Requires or may require concomitant treatment with any other medication likely to increase QT interval (e.g., paroxetine, fluoxetine, duloxetine, amiodarone).
  • Requires medication inhibiting CYP2D6.
  • Clinically significant ECG abnormality that could be a safety issue in the study, including QT interval value corrected for heart rate using the Fridericia's formula (QTcF) > 430 msec for males and > 450 msec for females.
  • Familial or personal history of long QT syndrome or with another risk factor for Torsade de Pointes.
  • History of myocardial infarction based on medical history or ECG findings at Screening.
  • Syncope.
  • Woman of child-bearing potential, or man, who is unwilling or unable to use accepted methods of birth control.
  • Woman with a positive pregnancy test, is lactating, or is planning to become pregnant during the study.
  • Participated in another clinical study that was completed within 6 months prior to Screening or has previously participated in > 2 clinical studies with experimental medication within the past 2 years.

Study Design

Enrollment

380 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Placebo to Roluperidone

Placebo administered as an oral dose daily from Day 1 to Week 12 (Phase A), then Roluperidone 64 mg administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B).

experimental: Placebo to Antipsychotic

Placebo administered as an oral dose daily from Day 1 to Week 12 (Phase A), then antipsychotic (risperidone 4 mg, aripiprazole 10 mg, or olanzapine 10 mg) administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B).

experimental: Roluperidone to Roluperidone

Roluperidone 64 mg administered as an oral dose daily from Day 1 to Week 12 (Phase A), then Roluperidone 64 mg administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B).

experimental: Roluperidone to Antipsychotic

Roluperidone 64 mg administered as an oral dose daily from Day 1 to Week 12 (Phase A), then antipsychotic (risperidone 4 mg, aripiprazole 10 mg, or olanzapine 10 mg) administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B).

Interventions

Roluperidone

Roluperidone 64 mg

risperidone

risperidone 4 mg

aripiprazole

aripiprazole 10 mg

olanzapine

olanzapine 10 mg

Placebo

Placebo

Primary outcome measure

  • Change from Baseline to Week 12 in Marder Negative Symptoms Factor Score (NSFS) [ Time Frame: Phase A: Screening, Baseline, Weeks 2, 4, 8, 12 ]

Central Contacts and Locations

Central contacts

Chief Operating Officer

617-600-7373info@minervaneurosciences.com

Locations

Clinical Innovations, Inc. dba CITrials

Recruiting

Bellflower, California, United States, 90706

ProScience Research Group

Recruiting

Culver City, California, United States, 90230

Collaborative Neuroscience Research, LLC

Recruiting

Garden Grove, California, United States, 92845

Clinical Innovations, Inc. dba CITrials

Recruiting

Riverside, California, United States, 92506

Velocity Clinical Research, Hallandale Beach

Recruiting

Hallandale, Florida, United States, 33009

Behavioral Clinical Research, Inc.

Recruiting

Hollywood, Florida, United States, 33021

ForCare Clinical Research

Recruiting

Tampa, Florida, United States, 33613

Atlanta Center for Medical Research, LLC

Recruiting

Atlanta, Georgia, United States, 30331

CenExel iResearch, LLC

Recruiting

Decatur, Georgia, United States, 30030

CBH Health, LLC dba CenExel

Recruiting

Gaithersburg, Maryland, United States, 20877

Hassman Research Institute, LLC dba CenExel

Recruiting

Marlton, New Jersey, United States, 08053

New York State Psychiatric Institute

Recruiting

New York, New York, United States, 10032

Pillar Clinical Research, LLC

Recruiting

Richardson, Texas, United States, 75080

More Information

Sponsor

Minerva Neurosciences

Last update posted

Jul 28, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Minerva Neurosciences on 2026-07-28.