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

NCT04512066 | Completed Phase 2 Results FDA Drug

• 1 other identifier: BP41743
• Study Type: interventional
• Target: 287
• Locations: 4 countries
• Sites: 40

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

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4

  The PANSS is a 30-item rating scale that evaluates positive, negative, and other symptoms in patients with schizophrenia. The Positive subscale is a 7-item scale that assesses features in schizophrenia that are not present in a normal mental state. The Negative subscale is a 7-item scale that assesses features absent in schizophrenia but present in those with a normal mental state. Items are rated on a 7-point scale, where 1 = absent and 7 = extreme, for a maximum score of 49 for each scale. The General subscale is a 16-item scale that assesses the overall severity of schizophrenia and the risk of aggression. Items are rated on the same scale, with a minimum score of 16 and a maximum score of 112. Total scores are calculated by adding subscale scores together, for a minimum score of 30 and a maximum score of 210. Higher scores indicate higher severity.

  Week 4 (Day 28)

Secondary Outcomes (10)

• Change From Baseline in PANSS Factor Scores at Week 4

  Week 4 (Day 28)

• Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score

  Baseline to Week 12

• Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores

  Week 4 (Day 28)

• Clinical Global Impression - Improvement (CGI-I) Scores

  Week 4 (Day 28)

• PANSS Total Score at Week 12

  Week 12

Study Arms (4)

150 mg Once Daily (QD) RO6889450

EXPERIMENTAL

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

Drug: RO6889450

45 mg QD RO6889450

EXPERIMENTAL

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

Drug: RO6889450

Placebo

PLACEBO COMPARATOR

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).

Drug: Placebo

4 mg QD Risperidone

ACTIVE COMPARATOR

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

Drug: Risperidone

Interventions

RO6889450 DRUG

Participants will receive oral RO6889450 QD.

150 mg Once Daily (QD) RO6889450; 45 mg QD RO6889450

Placebo DRUG

Participants will receive oral placebo QD.

Placebo

Risperidone DRUG

Participants will receive oral risperidone QD.

4 mg QD Risperidone

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (40)

Woodland International Research Group Inc.

Little Rock, Arkansas, 72211, United States

Location

CITrials, Inc.

Bellflower, California, 90706, United States

Location

ProScience Research Group

Culver City, California, 90230, United States

Location

Collaborative Neuroscience Network, Inc.

Garden Grove, California, 92845, United States

Location

California Clinical Trials Medical Group managed by Parexel

Glendale, California, 91206, United States

Location

Synergy San Diego

Lemon Grove, California, 91945, United States

Location

NRC Research Institute

Orange, California, 92868, United States

Location

ASCLEPES Research Centers

Panorama City, California, 91402, United States

Location

CNRI - Los Angeles, LLC

Pico Rivera, California, 90660, United States

Location

CITrials, Inc.

Riverside, California, 92506, United States

Location

California Neuropsychopharmacology Clinical Research Institute, LLC

San Diego, California, 92102, United States

Location

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

San Diego, California, 92103, United States

Location

Schuster Medical Research Institute

Sherman Oaks, California, 91403, United States

Location

Galiz Research, LLC

Hialeah, Florida, 33016, United States

Location

Innovative Clinical Research, Inc.

Lauderhill, Florida, 33319, United States

Location

Premier Clinical Research Institute - Miami - BTC - PPDS

Miami, Florida, 33122, United States

Location

Research Centers of America - ERG

Oakland Park, Florida, 33334, United States

Location

Atlanta Center For Medical Research

Atlanta, Georgia, 30331, United States

Location

Uptown Research Institute

Chicago, Illinois, 60640, United States

Location

CBH Health LLC

Gaithersburg, Maryland, 20877, United States

Location

Neuro-Behavioral Clinical Research, Inc.

Canton, Ohio, 44718, United States

Location

Midwest Clinical Research Center - ERG - PPDS

Dayton, Ohio, 45415, United States

Location

Community Clinical Research Inc.

Austin, Texas, 78754, United States

Location

Pillar Clinical Research LLC

Garland, Texas, 75042, United States

Location

National Center of Neurology and Psychiatry

Tokyo, 187-8551, Japan

Location

Seishinkai Okehazama Hospital Fujita Kokoro Care Center

Toyoake, 470-1168, Japan

Location

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

Saint Petersburg, Sankt-Peterburg, 188357, Russia

Location

Leningradskiy Regional Psychoneurologic Dispensary

Saint Petersburg, Sankt-Peterburg, 188820, Russia

Location

Psychiatric Hospital St Nicholas the Wonderworker

Saint Petersburg, Sankt-Peterburg, 190121, Russia

Location

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

Saint Petersburg, Sankt-Peterburg, 197341, Russia

Location

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

Sankt-peterburg, Vladimirskaya Oblast’, 192019, Russia

Location

Saratov regional clinical psychoneurological hospital St Sofii

Saratov, 410060, Russia

Location

Stavropol Regional Psychiatry Hospital #2

Stavropol, 357034, Russia

Location

Tomsk National Scientific Medical Center of Russian Academy of Sciences

Tomsk, 634009, Russia

Location

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

Kharkiv, Kharkiv Governorate, 61068, Ukraine

Location

Public NPE Kherson Regional Institution of Mental Care of Kherson RC

Kherson, Kherson Governorate, 73488, Ukraine

Location

Kyiv Medical Regional Union Psychiatry

Kylv, KIEV Governorate, 04080, Ukraine

Location

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

Smila, KIEV Governorate, 20708, Ukraine

Location

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

Vinnytsia, Podolia Governorate, 21037, Ukraine

Location

Poltava Regional Psychiatry Hospital

Poltava, Poltava Governorate, 36030, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 36369028 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Risperidone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

1-800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2020
• First Posted: August 13, 2020
• Study Start: September 8, 2020
• Primary Completion: June 21, 2022
• Study Completion: June 21, 2022
• Last Updated: October 10, 2023
• Results First Posted: October 10, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share

Locations

RU (8); JP (2); US (24); UA (6)