A Study to Assess the Effects of RO6889450 (Ralmitaront) in Participants With Schizophrenia or Schizoaffective Disorder and Negative Symptoms

Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Effects of RO6889450 (Ralmitaront) in Patients With Schizophrenia or Schizoaffective Disorder and Negative Symptoms

This study investigates the effects of RO6889450 on the negative symptoms associated with schizophrenia and schizoaffective disorder.

Study Overview

• Status: Terminated
• Conditions: Schizophrenia, Schizoaffective Disorder
• Intervention / Treatment: Drug: RO6889450; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BP40283 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global-roche-genentech-trials@gene.com

Study Locations

• Japan
  • Chiba, Japan, 272-8516
    • Kohnodai Hp., National Center for Global Health and Medicine
  • Kunigami, Japan, 904-1201
    • National Hospital Organization Ryukyu Hospital
  • Shirakawa, Japan, 961-0021
    • Nankokokorono Clinic
  • Tokyo, Japan, 187-8551
    • National Center of Neurology and Psychiatry
  • Toyoake, Japan, 470-1168
    • Seishinkai Okehazama Hospital Fujita Kokoro Care Center
  • Yokohama-shi, Japan, 223-0062
    • Hiyoshi Hospital
• Spain
  • Cordoba, Spain, 14004
    • C.H. Regional Reina Sofia - PPDS
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28922
    • Hosp Univ Fundacion Alcorcon
  • Malaga, Spain, 29010
    • Hospital Regional Universitario de Malaga ? Hospital General
  • Salamanca, Spain, 37007
    • Complejo Asistencial Universitario de Salamanca ? H. Clinico
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Hospital Universitario Central de Asturias
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Corporacio Sanitaria Parc Tauli
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
• Ukraine
  • KIEV Governorate
    • Dnipro, KIEV Governorate, Ukraine, 49005
      • ME Dnipropetrovsk Regional Clinical Hospital n.a. I.I Mechnykov Dnipropetrovsk Regional Council
    • Kyiv, KIEV Governorate, Ukraine, 01033
      • Medical and diagnostic center Healthy and Happy of Limited Liability Company Healthy and Happy
    • Uzhhorod, KIEV Governorate, Ukraine, 88000
      • Zakarpattia Regional Clinical Hospital n.a. Andrii Novak
  • Katerynoslav Governorate
    • Nove, Katerynoslav Governorate, Ukraine, 25491
      • CNCE Regional Clinical Psychiatric Hospital of Kirovohrad Regional Council
  • Kharkiv Governorate
    • Kharkiv, Kharkiv Governorate, Ukraine, 61068
      • Communal Non-Commercial Enterprise of Kharkiv RC Regional clinical psychiatric hospital #3
  • Kherson Governorate
    • Kherson, Kherson Governorate, Ukraine, 73488
      • Public NPE Kherson Regional Institution of Mental Care of Kherson RC
    • Odesa, Kherson Governorate, Ukraine, 65006
      • Municipal Non-Commercial Enterprise Odesa RMC for Mental Health of Odessa Regional Council
  • Podolia Governorate
    • Vinnytsia, Podolia Governorate, Ukraine, 21037
      • Communal NPE Vinnytsia Reg. Clin. Psychoneurolog. Hosp. n.a. O.I. Yushchenko of Vinnytsia RC
• United States
  • California
    • Bellflower, California, United States, 90706
      • CITrials, Inc.
    • Costa Mesa, California, United States, 92626
      • CITrials - Santa Ana
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, Inc.
    • Glendale, California, United States, 91206
      • California Clinical Trials
    • Lemon Grove, California, United States, 91945
      • Synergy San Diego
    • Montclair, California, United States, 91763
      • Catalina Research Institute LLC - MRA
    • Panorama City, California, United States, 91402
      • ASCLEPES Research Centers
    • Riverside, California, United States, 92506
      • CITrials, Inc.
    • San Diego, California, United States, 92102
      • California Neuropsychopharmacology Clinical Research Institute, LLC
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
    • Torrance, California, United States, 90502
      • Collaborative Neuroscience Network Inc.
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale School of Medicine - CT Mental Health Center (CMHC) - Schizophrenia Research Clinic
  • Florida
    • Lauderhill, Florida, United States, 33319
      • Innovative Clinical Research, Inc.
    • Leesburg, Florida, United States, 34748
      • Lifestream Behavioral Center
    • Maitland, Florida, United States, 32751
      • Accel Research Sites - Maitland - ERN - PPDS
    • Miami, Florida, United States, 33122
      • Premier Clinical Research Institute - Miami - BTC - PPDS
    • Miami, Florida, United States, 33135
      • Advanced Research Institute of Miami
    • Okeechobee, Florida, United States, 34972
      • Health Synergy Clinical Research
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611-2987
      • Northwestern University
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • CBH Health
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Michigan Clinical Research Institute PC - Clinedge - PPDS
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Centers
  • Missouri
    • Saint Louis, Missouri, United States, 63132
      • Millennium Psychiatric Associates, LLC
    • Saint Louis, Missouri, United States, 63128
      • Psych Care Consultants Research
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute
    • New York, New York, United States, 10035
      • Manhattan Psychiatric Center; Psychopharmacology Research Unit
  • Texas
    • Fort Worth, Texas, United States, 76104
      • JPS Health Network
    • Garland, Texas, United States, 75042
      • Pillar Clinical Research LLC
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Irving, Texas, United States, 75062
      • University Hills Clinical Research
    • Missouri City, Texas, United States, 77459
      • The Solace Center
    • Richmond, Texas, United States, 77406
      • Psychiatry & Behavioral Center
    • Richmond, Texas, United States, 77407
      • @ Health Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with a Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnosis of schizophrenia or schizoaffective disorder as confirmed by the Mini International Neuropsychiatric Interview (MINI)
• Part B only: Stable treatment with a dopamine/serotonin (D2/5HT2A) antagonist or pure D2 antagonist(s), or a D2 partial agonist for a minimum of 6 months and receiving no more than two antipsychotics
• Medically stable during the 3 months prior to study entry
• Participant is an outpatient with no psychiatric hospitalizations within the prior 6 months
• PANSS negative symptom factor score of 18 or higher
• The following rating on items of the PANSS: (a) less than 5 on G8 (uncooperativeness), P1 (delusions), P3 (hallucinations), P4 (excitement/hyperactivity), and P6 (suspiciousness/persecution); (b) less than 4 on P7 (hostility), and G14 (poor impulse control)
• Has an informant who is considered reliable by the Investigator
• Body mass index (BMI) between 18-40 kg/m2 inclusive
• Female participants are eligible to participate if not pregnant, not breastfeeding and 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

Exclusion Criteria:

• Moderate to severe substance use disorder within six months of study entry (excluding nicotine or caffeine) as defined by DSM-5
• Extrapyramidal symptom rating scale (ESRS-A CGI) subscore greater than or equal to 3
• Other current DSM-5 diagnosis (e.g., bipolar disorder, major depressive disorder)
• PANSS item G6 (depression) greater than or equal to 5
• Significant risk of suicide or harming him- or herself or others according to the Investigator's judgment
• A prior or current general medical condition that might be impairing cognition or other psychiatric functioning
• Positive result at screening for hepatitis B surface antigen (HBsAg), hepatitis C (HCV), or HIV-1 and HIV-2. HCV antibody positive participants are eligible if HCV RNA is negative
• Tardive dyskinesia that is moderate to severe or requires treatment
• History of neuroleptic malignant syndrome
• Average triplicate Fridericia's Correction Formula (QTcF) interval greater than 450 milliseconds (msec) for males and 470 msec for females or other clinically significant abnormality on screening electrocardiogram (ECG) based on centralized reading
• Clinically significant abnormalities in laboratory safety test results
• Significant or unstable physical condition that in the investigator's judgment might require a change in medication or hospitalization during the course of the study
• On more than one antidepressant, or if on one antidepressant, a change in dose within 28 days prior to screening
• History of clozapine treatment
• History of treatment with electroconvulsive therapy (ECT)
• Concomitant use of prohibited medications
• Positive urine drug screen for amphetamines, methamphetamines, opiates, buprenomorphine, methadone, cannabinoids, cocaine, and barbiturates
• Receipt of an investigational drug within 28 days or five times the half-life of the investigational drug (whichever is longer) before the first study drug administration
• Donation of blood over 400 mL within 3 months prior to screening
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Monotherapy; Participants will receive RO6889450 or a dose-matched placebo. NOTE: Part A has completed enrollment.	Drug: RO6889450; Participants will receive a once-daily, oral dose of RO6889450 for 12 weeks.; Drug: Placebo; Participants will receive a once-daily, oral dose of placebo matched to RO6889450 for 12 weeks.
Experimental: Part B: Add-On Therapy; Participants will receive a low or high dose of RO6889450 or a dose-matched placebo in addition to their usual anti-psychotic treatment(s).	Drug: RO6889450; Participants will receive a once-daily, oral dose of RO6889450 for 12 weeks.; Drug: Placebo; Participants will receive a once-daily, oral dose of placebo matched to RO6889450 for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline at Week 12 in Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Clinical Global Impression Severity (CGI-S) Overall Scores	Baseline to week 12
Change from Baseline in CGI-S Negative Symptoms Scores	Baseline to week 12
Clinical Global Impression - Improvement (CGI-I) Overall Scores	Week 12
CGI-I Negative Symptoms Scores	Week 12
Change from Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores	Baseline to week 12
Change from Baseline in Positive and Negative Syndrome Scale (PANSS) Symptom Factor Scores	Baseline to week 12
Change from Baseline in Brief Negative Symptom Scale (BNSS) Total Scores	Baseline to week 12
Change from Baseline in Brief Negative Symptom Scale (BNSS) Symptom Factor Scores	Baseline to week 12
Change from Baseline in Defeatist Performance Attitude Scale (DPAS) Scores	Baseline to week 12
Percentage of Participants with Adverse Events (AE)	Baseline through the end of the follow-up period (approximately 16 weeks)
Change from Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Scores	Baseline through the end of the follow-up period (approximately 16 weeks)
Change from Baseline in Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A)	Baseline through the end of the follow-up period (approximately 16 weeks)
Area Under the Curve at Steady State (AUCss) of RO6889450	At pre-defined intervals from Day 7 through the end of the follow-up period (approximately 16 weeks)
Maximum Serum Concentration (Cmax) of RO6889450	At pre-defined intervals from Day 7 through the end of the follow-up period (approximately 16 weeks)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2018
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): May 8, 2023

Study Registration Dates

• First Submitted: September 12, 2018
• First Submitted That Met QC Criteria: September 12, 2018
• First Posted (Actual): September 13, 2018

Study Record Updates

• Last Update Posted (Actual): May 18, 2023
• Last Update Submitted That Met QC Criteria: May 16, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders
• Other Study ID Numbers: BP40283

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No