Clinical trial NCT03669640: A Study to Assess the Effects of RO6889450 (Ralmitaront) in Participants With Schizophrenia or Schizoaffective Disorder and Negative Symptoms
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Schizophrenia, Schizoaffective Disorder
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-09-13
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Clinical Global Impression Severity (CGI-S) Overall Scores
timeFrame: Baseline to week 12
measure: CGI-S Negative Symptoms (NS) Scores
timeFrame: Baseline to week 12
measure: Clinical Global Impression - Improvement (CGI-I) Overall Scores
timeFrame: Up to Week 12 (Day 84)
measure: CGI-I Negative Symptoms Scores
timeFrame: Up to Week 12 (Day 84)
measure: Positive and Negative Syndrome Scale (PANSS) Total Scores
timeFrame: Baseline to week 12
measure: PANSS Symptom Factor Scores
timeFrame: Baseline to week 12
measure: Brief Negative Symptom Scale (BNSS) Total Scores
timeFrame: Baseline to week 12
measure: Defeatist Performance Attitude Scale (DPAS) Scores
timeFrame: Baseline to week 12
measure: Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline through Day 84
measure: Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A)
timeFrame: Baseline through Day 84
measure: Maximum Serum Concentration (Cmax) of RO6889450
timeFrame: Day 42
measure: Area Under the Curve at Steady State (AUCss) of RO6889450
timeFrame: Day 42
Other outcomes:
Locations:
city: Bellflower
country: United States
facility: CITrials, Inc.
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, Inc.
state: California
city: Glendale
country: United States
facility: California Clinical Trials
state: California
city: Lemon Grove
country: United States
facility: Synergy San Diego
state: California
city: Montclair
country: United States
facility: Catalina Research Institute LLC - MRA
state: California
city: Riverside
country: United States
facility: CITrials, Inc.
state: California
city: San Diego
country: United States
facility: California Neuropsychopharmacology Clinical Research Institute, LLC
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Network Inc.
state: California
city: New Haven
country: United States
facility: Yale School of Medicine - CT Mental Health Center (CMHC) - Schizophrenia Research Clinic
state: Connecticut
city: Lauderhill
country: United States
facility: Innovative Clinical Research, Inc.
state: Florida
city: Leesburg
country: United States
facility: Lifestream Behavioral Center
state: Florida
city: Miami
country: United States
facility: Advanced Research Institute of Miami
state: Florida
city: Okeechobee
country: United States
facility: Health Synergy Clinical Research
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Gaithersburg
country: United States
facility: CBH Health
state: Maryland
city: Flowood
country: United States
facility: Precise Research Centers
state: Mississippi
city: Saint Louis
country: United States
facility: Psych Care Consultants Research
state: Missouri
city: Saint Louis
country: United States
facility: Millennium Psychiatric Associates, LLC
state: Missouri
city: New York
country: United States
facility: Manhattan Psychiatric Center; Psychopharmacology Research Unit
state: New York
city: Fort Worth
country: United States
facility: JPS Health Network
state: Texas
city: Garland
country: United States
facility: Pillar Clinical Research LLC
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Irving
country: United States
facility: University Hills Clinical Research
state: Texas
city: Missouri City
country: United States
facility: The Solace Center
state: Texas
city: Richmond
country: United States
facility: Psychiatry & Behavioral Center
state: Texas
city: Richmond
country: United States
facility: @ Health Texas
state: Texas
city: Chiba
country: Japan
facility: Kohnodai Hp., National Center for Global Health and Medicine
city: Kunigami
country: Japan
facility: National Hospital Organization Ryukyu Hospital
city: Tokyo
country: Japan
facility: National Center of Neurology and Psychiatry
city: Toyoake
country: Japan
facility: Seishinkai Okehazama Hospital Fujita Kokoro Care Center
city: Yokohama-shi
country: Japan
facility: Hiyoshi Hospital
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Cordoba
country: Spain
facility: C.H. Regional Reina Sofia - PPDS
city: Madrid
country: Spain
facility: Hosp Univ Fundacion Alcorcon
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca ? H. Clinico
city: Nove
country: Ukraine
facility: CNCE Regional Clinical Psychiatric Hospital of Kirovohrad Regional Council
state: Katerynoslav Governorate
city: Kharkiv
country: Ukraine
facility: Communal Non-Commercial Enterprise of Kharkiv RC Regional clinical psychiatric hospital #3
state: Kharkiv Governorate
city: Kherson
country: Ukraine
facility: Public NPE Kherson Regional Institution of Mental Care of Kherson RC
state: Kherson Governorate
city: Odesa
country: Ukraine
facility: Municipal Non-Commercial Enterprise Odesa RMC for Mental Health of Odessa Regional Council
state: Kherson Governorate
city: Dnipro
country: Ukraine
facility: ME Dnipropetrovsk Regional Clinical Hospital n.a. I.I Mechnykov Dnipropetrovsk Regional Council
state: KIEV Governorate
city: Uzhhorod
country: Ukraine
facility: Zakarpattia Regional Clinical Hospital n.a. Andrii Novak
state: KIEV Governorate
city: Vinnytsia
country: Ukraine
facility: Communal NPE Vinnytsia Reg. Clin. Psychoneurolog. Hosp. n.a. O.I. Yushchenko of Vinnytsia RC
state: Podolia Governorate
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: