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): 131
• Phase: Phase 2

Contacts and Locations

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
  • 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, 28922
    • Hosp Univ Fundacion Alcorcon
  • Salamanca, Spain, 37007
    • Complejo Asistencial Universitario de Salamanca ? H. Clinico
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Hospital Universitario Central de Asturias
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla
• Ukraine
  • KIEV Governorate
    • Dnipro, KIEV Governorate, Ukraine, 49005
      • ME Dnipropetrovsk Regional Clinical Hospital n.a. I.I Mechnykov Dnipropetrovsk Regional Council
    • 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.
    • 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
    • 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
    • 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, 60611-2908
      • Northwestern University
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • CBH Health
  • 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, 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	Measure Description	Time Frame
Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12	The BNSS is a 13-item instrument designed for clinical trials that measures the severity of the negative symptoms of schizophrenia in five domains. There are 13 items organized into 6 subscales (anhedonia, distress, asociality, avolition, blunted affect, and alogia), each rated on a 7-point scale (0-6) where 0 = absent symptoms and 6 = severe symptoms. The total score is calculated by summing the individual items (13) of each subscale and has a range of 0-78. The avolition/apathy subscale contains 2 items with a total score range of 0-12.	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression Severity (CGI-S) Overall Scores	The CGI-S is an absolute measure assessing how mentally ill the participant is at the time of the assessment on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). On the scale, the value 0 corresponds to 'not assessed', which will be excluded from the analyses. The values 1 to 7 will be transformed into the 0 to 6 range prior to statistical analysis for the question on the measure ("Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?"), making the total score range 0-6.	Baseline to week 12
CGI-S Negative Symptoms (NS) Scores	The CGI-S-NS is similar to the CGI-S and is assessed on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). On the scale, the value 0 corresponds to 'not assessed', which will be excluded from the analyses. The values 1 to 7 will be transformed into the 0 to 6 range prior to statistical analysis for the question on the measure, making the total score range 0-6.	Baseline to week 12
Clinical Global Impression - Improvement (CGI-I) Overall Scores	The CGI-I assesses how much the participant's condition has changed at the time of the assessment in comparison to their condition at baseline. It uses a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), where the value 0 corresponds to 'not assessed' and will be excluded from any analyses.	Up to Week 12 (Day 84)
CGI-I Negative Symptoms Scores	The CGI-I NS is similar to the CGI-I and assesses how much the participant's condition has changed at the time of the assessment in comparison to their condition at baseline. It uses a 7-point scale, where: = Very much improved; = Much improved; = Minimally improved; = No change; = Minimally worse; = Much worse; = Very much worse	Up to Week 12 (Day 84)
Positive and Negative Syndrome Scale (PANSS) Total Scores	The PANSS Marder factors examine schizophrenia symptoms in five domains: positive symptoms, negative symptoms, disorganized thought, uncontrolled hostility/excitement, and depression/anxiety. The Marder factor positive symptom score (range = 8-56) measures responses to 8 items (P1,P3,P5,P6,N7,G1,G9,G12) while the negative symptom factor score (range = 7-49) consists of 7 items (N1,N2,N3,N4,N6,G7,G16). Each item is scored on a scale of 1-7, where 1 = an absence of symptoms and 7 = extreme symptoms. The positive and negative syndrome scale total score is the sum of the scores from each domain (range = 15-105); higher scores indicate greater severity of symptoms.	Baseline to week 12
PANSS Symptom Factor Scores	The PANSS Marder factors examine schizophrenia symptoms in five domains: positive symptoms, negative symptoms, disorganized thought, uncontrolled hostility/excitement, and depression/anxiety. The Marder factor positive symptom score (range = 8-56) measures responses to 8 items (P1,P3,P5,P6,N7,G1,G9,G12) while the negative symptom factor score (range = 7-49) consists of 7 items (N1,N2,N3,N4,N6,G7,G16). Each item is scored on a scale of 1-7, where 1 = an absence of symptoms and 7 = extreme symptoms.	Baseline to week 12
Brief Negative Symptom Scale (BNSS) Total Scores	The BNSS is a 13-item instrument designed for clinical trials that measures the severity of the negative symptoms of schizophrenia in five domains. There are 13 items organized into 6 subscales (anhedonia, distress, asociality, avolition, blunted affect, and alogia), each rated on a 7-point scale (0-6) where 0 = absent symptoms and 6 = severe symptoms. The total score is calculated by summing the individual items (13) of each subscale and has a range of 0-78.	Baseline to week 12
Defeatist Performance Attitude Scale (DPAS) Scores	The DPAS is a 15-item, patient-rated assessment that evaluates expectations of failures or self-defeating beliefs related to prior failed experiences as well as illness on a 7-point Likert scale (total range = 15-105) ranging from totally agree (1) to totally disagree (7).	Baseline to week 12
Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS)	The C-SSRS is a suicide risk assessment tool used to help identify the risk of suicide.	Baseline through Day 84
Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A)	The ESRS-A is used to evaluate the presence and severity of extrapyramidal symptoms. Items are rated on a scale of 0 (no symptoms) to 5 (extreme symptoms).	Baseline through Day 84
Maximum Serum Concentration (Cmax) of RO6889450		Day 42
Area Under the Curve at Steady State (AUCss) of RO6889450		Day 42

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 12, 2023
• Study Completion (Actual): March 12, 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): August 12, 2024
• Last Update Submitted That Met QC Criteria: August 6, 2024
• Last Verified: August 1, 2024

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