A Trial of the Efficacy and the Safety of RO6889450 (Ralmitaront) vs Placebo in Patients With an Acute Exacerbation of Schizophrenia or Schizoaffective Disorder

NCT ID: NCT04512066

Last Updated: 2023-10-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 287 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-08
• Study Completion Date: 2022-06-21

Brief Summary

This study will investigate the efficacy and safety of RO6889450 as monotherapy in participants experiencing an acute exacerbation of symptoms of schizophrenia or schizoaffective disorder.

Conditions

Schizophrenia, Schizoaffective Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

150 mg Once Daily (QD) RO6889450

Participants will receive 150 mg of RO6889450 QD for 4 weeks or 12 weeks or 48 weeks.

Group Type: EXPERIMENTAL

RO6889450

Intervention Type: DRUG

Participants will receive oral RO6889450 QD.

45 mg QD RO6889450

Participants will receive 45 mg of RO6889450 QD for 4 weeks or 12 weeks or 48 weeks.

Group Type: EXPERIMENTAL

RO6889450

Intervention Type: DRUG

Participants will receive oral RO6889450 QD.

Placebo

Participants will receive oral placebo QD for 4 weeks. Participants from this arm that continue to the extension period will be randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks or additional 44 weeks (optional 36-Week Safety Extension Phase).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive oral placebo QD.

4 mg QD Risperidone

Participants will receive 4 mg of risperidone QD for 4 weeks or 12 weeks or 48 weeks.

Group Type: ACTIVE_COMPARATOR

Risperidone

Intervention Type: DRUG

Participants will receive oral risperidone QD.

Interventions

RO6889450

Participants will receive oral RO6889450 QD.

Intervention Type: DRUG

Placebo

Participants will receive oral placebo QD.

Intervention Type: DRUG

Risperidone

Participants will receive oral risperidone QD.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participant must be 18 to 45 years of age inclusive
• Participants with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of schizophrenia or schizoaffective disorder as confirmed by the Mini International Neuropsychiatric Interview (MINI)
• Disease duration </=10 years
• Have a current acute exacerbation of schizophrenia of no more than 8 weeks before screening visit and no current signs of apparent lack of treatment response
• At the time of screening, the participant needs to be either hospitalized or requiring inpatient psychiatric care according to clinical judgment. If the participant has been hospitalized for the current exacerbation, the hospitalization has to be of a maximum of 1 week prior to screening.
• In previous exacerbations and hospitalizations, the subject has shown a pattern of response to appropriate antipsychotic treatment
• Medically stable over a period of 3 months (non-psychiatric conditions) prior to screening visit and not expected to require hospitalization or change of treatment for non-psychiatric conditions for the duration of the study
• Screening and baseline CGI-S >/=4 (moderate or worse)
• Screening and baseline PANSS total score >= 80
• Based on screening and baseline PANSS, scores of >/= 4 (moderate or worse) on 2 or more of the following items: delusions, conceptual disorganization, unusual thought content, hallucinatory behavior, or suspiciousness/persecution
• Body mass index between 18 and 35 kg/m2 inclusive
• Male and female participants; female participants agree to remain abstinent or use acceptable contraceptive methods during the treatment period and for at least 28 days after the last dose of study drug

• Successful completion of the 12-week treatment period
• No signs or symptoms of worsening of the psychiatric or medical status that would preclude the patient from the participation in the 36-Week Safety Extension Phase or affect their ability to comply with the study requirements.

Exclusion Criteria

• Has been inpatient for > 1 week or had any other hospitalization for acute exacerbation of schizophrenia or schizoaffective disorder within the prior 8 weeks or signs of lack of response to antipsychotic treatment
• Disease duration > 10 years
• Is currently an inpatient on an involuntary basis
• Subject answers "yes" to "Suicidal Ideation" Item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) or any suicidal behavior on the Columbia-Suicide Severity Rating Scale (C-SSRS) assessment within one month from screening or between screening and baseline
• Lifetime history of homicidal behavior
• Moderate to severe substance use disorder within six months (excluding nicotine) as defined by DSM-5
• Other current DSM-5 diagnosis (e.g., bipolar disorder, major depressive disorder)
• A prior or current general medical condition that might be impairing cognition or other psychiatric functioning (e.g., migraine headaches requiring prophylaxis treatment, head trauma, dementia, seizure disorder, stroke; or neurodegenerative, inflammatory, infectious, neoplastic, toxic, metabolic, or endocrine conditions)
• Clinically significant abnormalities in laboratory safety test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis), including a) Aspartate aminotransferase (AST), OR alanine aminotransferase (ALT) 2 x upper limit of normal (ULN), OR total bilirubin > 1.5 ULN with the exception of known Gilbert syndrome. b) Serum creatinine > 1.5 ULN
• Positive result at screening for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV, untreated), or human immunodeficiency virus (HIV)-1 and -2. HCV participants who have been successfully treated and who test negative for HCV RNA are eligible for entry into the study
• Tardive dyskinesia that is moderate to severe or requires treatment
• History of neuroleptic malignant syndrome
• Average triplicate QTcF interval greater than 450 msec for males and 470 msec for females or other clinically significant abnormality on screening ECG based on centralized reading
• Participant for whom risperidone is contraindicated or who have a documented history of lack of response or intolerance to risperidone or paliperidone or participants with known hypersensitivity to risperidone, paliperidone, or to any excipients in Risperdal
• Participant treated with a long acting injectable antipsychotic or other antipsychotics that cannot be washed-out within the allotted screening period
• History of electro-convulsive therapy (ECT) for any reason
• Participant treated with clozapine at any dose within 12 months of screening visit or participants treated with clozapine at 200 mg/day or above at any time; low dose (< 200mg/day) use for insomnia or dyskinesia longer than 12 months prior to screening visit is permitted
• Participants currently receiving a psychotropic or other medication used as a psychotropic, which cannot be discontinued during the screening period
• Positive urine drug screen for amphetamines, methamphetamines, opiates, buprenorphine, methadone, cocaine and barbiturates. In case of positive urine drug screen for cannabinoids, the participant may be allowed to enter the study if approved by Medical Monitor
• Participant has previously received RO6889450
• Participant received an investigational drug within 28 days or five times the half-life of the investigational drug prior to the first study drug administration
• Diagnosis of COVID-19 infection (confirmed or presumptive) 4 weeks prior to screening or during screening. Participants can be re-screened after 4 weeks of full recovery in addition to investigator and/or institutional approval to enroll

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Woodland International Research Group Inc.

Little Rock, Arkansas, United States

CITrials, Inc.

Bellflower, California, United States

ProScience Research Group

Culver City, California, United States

Collaborative Neuroscience Network, Inc.

Garden Grove, California, United States

California Clinical Trials Medical Group managed by Parexel

Glendale, California, United States

Synergy San Diego

Lemon Grove, California, United States

NRC Research Institute

Orange, California, United States

ASCLEPES Research Centers

Panorama City, California, United States

CNRI - Los Angeles, LLC

Pico Rivera, California, United States

CITrials, Inc.

Riverside, California, United States

California Neuropsychopharmacology Clinical Research Institute, LLC

San Diego, California, United States

Artemis Institute For Clinical Research LLC - San Diego - ClinEdge - PPDS

San Diego, California, United States

Schuster Medical Research Institute

Sherman Oaks, California, United States

Galiz Research, LLC

Hialeah, Florida, United States

Innovative Clinical Research, Inc.

Lauderhill, Florida, United States

Premier Clinical Research Institute - Miami - BTC - PPDS

Miami, Florida, United States

Research Centers of America - ERG

Oakland Park, Florida, United States

Atlanta Center For Medical Research

Atlanta, Georgia, United States

Uptown Research Institute

Chicago, Illinois, United States

CBH Health LLC

Gaithersburg, Maryland, United States

Neuro-Behavioral Clinical Research, Inc.

Canton, Ohio, United States

Midwest Clinical Research Center - ERG - PPDS

Dayton, Ohio, United States

Community Clinical Research Inc.

Austin, Texas, United States

Pillar Clinical Research LLC

Garland, Texas, United States

National Center of Neurology and Psychiatry

Tokyo, , Japan

Seishinkai Okehazama Hospital Fujita Kokoro Care Center

Toyoake, , Japan

Psychiatry Hospital #1 n.a. P.P.Kashchenko

Saint Petersburg, Sankt-Peterburg, Russia

Leningradskiy Regional Psychoneurologic Dispensary

Saint Petersburg, Sankt-Peterburg, Russia

Psychiatric Hospital St Nicholas the Wonderworker

Saint Petersburg, Sankt-Peterburg, Russia

City Psychiatry Hospital #3 n.a. I.I. Skvortsov-Stepanov

Saint Petersburg, Sankt-Peterburg, Russia

FSBI National Medical Research Centre of Psychiatry and Neurology n.a. V.M. Bekhterev of MoH of RF

Sankt-peterburg, Vladimirskaya Oblast’, Russia

Saratov regional clinical psychoneurological hospital St Sofii

Saratov, , Russia

Stavropol Regional Psychiatry Hospital #2

Stavropol, , Russia

Tomsk National Scientific Medical Center of Russian Academy of Sciences

Tomsk, , Russia

Communal Non-Commercial Enterprise of Kharkiv RC Regional clinical psychiatric hospital #3

Kharkiv, Kharkiv Governorate, Ukraine

Public NPE Kherson Regional Institution of Mental Care of Kherson RC

Kherson, Kherson Governorate, Ukraine

Kyiv Medical Regional Union Psychiatry

Kylv, KIEV Governorate, Ukraine

Communal Non-Commercial Enterprise Cherkasy Regional Psychiatric Hospital of Cherkasy RC

Smila, KIEV Governorate, Ukraine

Communal NPE Vinnytsia Reg. Clin. Psychoneurolog. Hosp. n.a. O.I. Yushchenko of Vinnytsia RC

Vinnytsia, Podolia Governorate, Ukraine

Poltava Regional Psychiatry Hospital

Poltava, Poltava Governorate, Ukraine

Countries

United States; Japan; Russia; Ukraine

References

Halff EF, Rutigliano G, Garcia-Hidalgo A, Howes OD. Trace amine-associated receptor 1 (TAAR1) agonism as a new treatment strategy for schizophrenia and related disorders. Trends Neurosci. 2023 Jan;46(1):60-74. doi: 10.1016/j.tins.2022.10.010. Epub 2022 Nov 8.

Reference Type: DERIVED

PMID: 36369028 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

BP41743

Identifier Type: -

Identifier Source: org_study_id