A Study to Assess the Effects of RO6889450 (Ralmitaront) in Participants With Schizophrenia or Schizoaffective Disorder and Negative Symptoms
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Interventions
- Drug: Placebo
- Registration Number
- NCT03669640
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study investigates the effects of RO6889450 on the negative symptoms associated with schizophrenia and schizoaffective disorder.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 131
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part B: Add-On Therapy Placebo Participants will receive a low or high dose of RO6889450 or a dose-matched placebo in addition to their usual anti-psychotic treatment(s). Part A: Monotherapy Placebo Participants will receive RO6889450 or a dose-matched placebo. NOTE: Part A has completed enrollment. Part A: Monotherapy RO6889450 Participants will receive RO6889450 or a dose-matched placebo. NOTE: Part A has completed enrollment. Part B: Add-On Therapy RO6889450 Participants will receive a low or high dose of RO6889450 or a dose-matched placebo in addition to their usual anti-psychotic treatment(s).
- Primary Outcome Measures
Name Time Method Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12 Baseline to 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.
- Secondary Outcome Measures
Name Time Method Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) Baseline through Day 84 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).
Clinical Global Impression Severity (CGI-S) Overall Scores Baseline to week 12 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.
Clinical Global Impression - Improvement (CGI-I) Overall Scores Up to Week 12 (Day 84) 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.
Brief Negative Symptom Scale (BNSS) Total Scores Baseline to 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.
Area Under the Curve at Steady State (AUCss) of RO6889450 Day 42 CGI-S Negative Symptoms (NS) Scores Baseline to week 12 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.
CGI-I Negative Symptoms Scores Up to Week 12 (Day 84) 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:
1. = Very much improved
2. = Much improved
3. = Minimally improved
4. = No change
5. = Minimally worse
6. = Much worse
7. = Very much worsePANSS Symptom Factor Scores Baseline to week 12 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.
Defeatist Performance Attitude Scale (DPAS) Scores Baseline to week 12 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).
Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS) Baseline through Day 84 The C-SSRS is a suicide risk assessment tool used to help identify the risk of suicide.
Positive and Negative Syndrome Scale (PANSS) Total Scores Baseline to week 12 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.
Maximum Serum Concentration (Cmax) of RO6889450 Day 42
Trial Locations
- Locations (44)
California Neuropsychopharmacology Clinical Research Institute, LLC
🇺🇸San Diego, California, United States
Synergy San Diego
🇺🇸Lemon Grove, California, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Advanced Research Institute of Miami
🇺🇸Miami, Florida, United States
Health Synergy Clinical Research
🇺🇸Okeechobee, Florida, United States
CBH Health
🇺🇸Gaithersburg, Maryland, United States
Psychiatry & Behavioral Center
🇺🇸Richmond, Texas, United States
CITrials, Inc.
🇺🇸Riverside, California, United States
Collaborative Neuroscience Network Inc.
🇺🇸Torrance, California, United States
University Hills Clinical Research
🇺🇸Irving, Texas, United States
Lifestream Behavioral Center
🇺🇸Leesburg, Florida, United States
Stanford University School of Medicine
🇺🇸Stanford, California, United States
Psych Care Consultants Research
🇺🇸Saint Louis, Missouri, United States
Manhattan Psychiatric Center; Psychopharmacology Research Unit
🇺🇸New York, New York, United States
Hosp Univ Fundacion Alcorcon
🇪🇸Madrid, Spain
Collaborative Neuroscience Network, Inc.
🇺🇸Garden Grove, California, United States
JPS Health Network
🇺🇸Fort Worth, Texas, United States
C.H. Regional Reina Sofia - PPDS
🇪🇸Cordoba, Spain
Innovative Clinical Research, Inc.
🇺🇸Lauderhill, Florida, United States
Millennium Psychiatric Associates, LLC
🇺🇸Saint Louis, Missouri, United States
Pillar Clinical Research LLC
🇺🇸Garland, Texas, United States
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Cantabria, Spain
@ Health Texas
🇺🇸Richmond, Texas, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Complejo Asistencial Universitario de Salamanca ? H. Clinico
🇪🇸Salamanca, Spain
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Public NPE Kherson Regional Institution of Mental Care of Kherson RC
🇺🇦Kherson, Kherson Governorate, Ukraine
Zakarpattia Regional Clinical Hospital n.a. Andrii Novak
🇺🇦Uzhhorod, KIEV Governorate, Ukraine
Kohnodai Hp., National Center for Global Health and Medicine
🇯🇵Chiba, Japan
National Hospital Organization Ryukyu Hospital
🇯🇵Kunigami, Japan
CNCE Regional Clinical Psychiatric Hospital of Kirovohrad Regional Council
🇺🇦Nove, Katerynoslav Governorate, Ukraine
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Asturias, Spain
Precise Research Centers
🇺🇸Flowood, Mississippi, United States
Municipal Non-Commercial Enterprise Odesa RMC for Mental Health of Odessa Regional Council
🇺🇦Odesa, Kherson Governorate, Ukraine
National Center of Neurology and Psychiatry
🇯🇵Tokyo, Japan
Seishinkai Okehazama Hospital Fujita Kokoro Care Center
🇯🇵Toyoake, Japan
Hiyoshi Hospital
🇯🇵Yokohama-shi, Japan
ME Dnipropetrovsk Regional Clinical Hospital n.a. I.I Mechnykov Dnipropetrovsk Regional Council
🇺🇦Dnipro, KIEV Governorate, Ukraine
Communal NPE Vinnytsia Reg. Clin. Psychoneurolog. Hosp. n.a. O.I. Yushchenko of Vinnytsia RC
🇺🇦Vinnytsia, Podolia Governorate, Ukraine
The Solace Center
🇺🇸Missouri City, Texas, United States
Catalina Research Institute LLC - MRA
🇺🇸Montclair, California, United States
California Clinical Trials
🇺🇸Glendale, California, United States
Communal Non-Commercial Enterprise of Kharkiv RC Regional clinical psychiatric hospital #3
🇺🇦Kharkiv, Kharkiv Governorate, Ukraine
Yale School of Medicine - CT Mental Health Center (CMHC) - Schizophrenia Research Clinic
🇺🇸New Haven, Connecticut, United States