Study to Evaluate Efficacy and Safety of Roluperidone in Adult Subjects With Negative Symptoms and Stable Positive Symptoms of Schizophrenia and to Evaluate the Relapse Rate of Roluperidone and Antipsychotic Medications

NCT07565428 | Recruiting Phase 3 FDA Drug

• 1 other identifier: MIN-101C19
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (1)

• Change from Baseline to Week 12 in Marder Negative Symptoms Factor Score (NSFS)

  The Marder Negative Symptoms Factor Score (NSFS) derived from the complete Positive and Negative Syndrome Scale (PANSS) has been the most frequently used scale in schizophrenia clinical studies focusing on negative symptoms. The PANSS measures comprehensive psychiatric symptoms, including positive, negative, and general symptoms. The full PANSS rates the patient on 30 different symptoms from 1 (absent) to 7 (extreme) based on an interview as well as reports of family members or primary care hospital workers. Negative symptoms will be defined by PANSS negative subscore (N1+N2+N3+N4+N5+N6+N7). Higher scores indicate more severe symptoms.

  Phase A: Screening, Baseline, Weeks 2, 4, 8, 12

Secondary Outcomes (2)

• Change from Baseline to Week 12 in the Personal and Social Performance (PSP) Total Score

  Phase A: Baseline and Weeks 4, 8, 12

• Change from Baseline to Week 12 in Clinical Global Impression of Severity (CGI-S)

  Phase A: Screening, Baseline, and Weeks 2, 4, 8, 12

Other Outcomes (2)

• Safety Assessments

  Phase A: Screening through Week 12; Phase B: Week 12 +1 Day through Week 54

• Number of Subjects who Relapse over 12 Weeks of Double-blind Treatment (Phase A) and over 40 Weeks of Treatment (Phase B)

  Phase A: Day 1 to Week 12; Phase B: Week 12 +1 Day to Week 52

Study Arms (4)

Placebo to Roluperidone

EXPERIMENTAL

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 52 (Phase B).

Drug: Roluperidone; Drug: Placebo

Placebo to Antipsychotic

EXPERIMENTAL

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 52 (Phase B).

Drug: risperidone; Drug: aripiprazole; Drug: olanzapine; Drug: Placebo

Roluperidone to Roluperidone

EXPERIMENTAL

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 52 (Phase B).

Drug: Roluperidone

Roluperidone to Antipsychotic

EXPERIMENTAL

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 52 (Phase B).

Drug: Roluperidone; Drug: risperidone; Drug: aripiprazole; Drug: olanzapine

Interventions

Roluperidone DRUG

Roluperidone 64 mg

Also known as: MIN-101

Placebo to Roluperidone; Roluperidone to Antipsychotic; Roluperidone to Roluperidone

risperidone DRUG

risperidone 4 mg

Placebo to Antipsychotic; Roluperidone to Antipsychotic

aripiprazole DRUG

aripiprazole 10 mg

Placebo to Antipsychotic; Roluperidone to Antipsychotic

olanzapine DRUG

olanzapine 10 mg

Placebo to Antipsychotic; Roluperidone to Antipsychotic

Placebo DRUG

Placebo

Placebo to Antipsychotic; Placebo to Roluperidone

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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 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 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.

You may not qualify if:

• 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, or urological disorder.
• History of seizures (subjects with a history of a single childhood febrile seizure may be enrolled in this study).

Sponsors & Collaborators

• Minerva Neurosciences: lead

Study Sites (2)

CBH Health, LLC dba CenExel

Gaithersburg, Maryland, 20877, United States

RECRUITING

Hassman Research Institute, LLC dba CenExel

Marlton, New Jersey, 08053, United States

RECRUITING

MeSH Terms

Interventions

roluperidone; Risperidone; Aripiprazole; Olanzapine

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzodiazepines; Benzazepines

Central Study Contacts

Chief Operating Officer

CONTACT

617-600-7380; jreilly@minervaneurosciences.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: May 4, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

US (2)