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

Schizophrenia, Schizoaffective Disorder Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03669640
• Other study ID #: BP40283
• Status: Terminated
• Phase: Phase 2
• Start date: December 4, 2018
• Est. completion date: May 8, 2023

Study information

• Verified date: May 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 128
• Est. completion date: May 8, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Psychotic Disorders
• Schizophrenia
• Schizophrenia, Schizoaffective Disorder

Intervention

Drug:
• RO6889450
Participants will receive a once-daily, oral dose of RO6889450 for 12 weeks.
• Placebo
Participants will receive a once-daily, oral dose of placebo matched to RO6889450 for 12 weeks.

Locations

Country	Name	City	State
Japan	Kohnodai Hp., National Center for Global Health and Medicine	Chiba
Japan	National Hospital Organization Ryukyu Hospital	Kunigami
Japan	Nankokokorono Clinic	Shirakawa
Japan	National Center of Neurology and Psychiatry	Tokyo
Japan	Seishinkai Okehazama Hospital Fujita Kokoro Care Center	Toyoake
Japan	Hiyoshi Hospital	Yokohama-shi
Spain	C.H. Regional Reina Sofia - PPDS	Cordoba
Spain	Hosp Univ Fundacion Alcorcon	Madrid
Spain	Hospital Universitario 12 De Octubre	Madrid
Spain	Hospital Regional Universitario de Malaga ? Hospital General	Malaga
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturias
Spain	Corporacio Sanitaria Parc Tauli	Sabadell	Barcelona
Spain	Complejo Asistencial Universitario de Salamanca ? H. Clinico	Salamanca
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Ukraine	ME Dnipropetrovsk Regional Clinical Hospital n.a. I.I Mechnykov Dnipropetrovsk Regional Council	Dnipro	KIEV Governorate
Ukraine	Communal Non-Commercial Enterprise of Kharkiv RC Regional clinical psychiatric hospital #3	Kharkiv	Kharkiv Governorate
Ukraine	Public NPE Kherson Regional Institution of Mental Care of Kherson RC	Kherson	Kherson Governorate
Ukraine	Medical and diagnostic center Healthy and Happy of Limited Liability Company Healthy and Happy	Kyiv	KIEV Governorate
Ukraine	CNCE Regional Clinical Psychiatric Hospital of Kirovohrad Regional Council	Nove	Katerynoslav Governorate
Ukraine	Municipal Non-Commercial Enterprise Odesa RMC for Mental Health of Odessa Regional Council	Odesa	Kherson Governorate
Ukraine	Zakarpattia Regional Clinical Hospital n.a. Andrii Novak	Uzhhorod	KIEV Governorate
Ukraine	Communal NPE Vinnytsia Reg. Clin. Psychoneurolog. Hosp. n.a. O.I. Yushchenko of Vinnytsia RC	Vinnytsia	Podolia Governorate
United States	Michigan Clinical Research Institute PC - Clinedge - PPDS	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	CITrials, Inc.	Bellflower	California
United States	Northwestern University	Chicago	Illinois
United States	CITrials - Santa Ana	Costa Mesa	California
United States	Precise Research Centers	Flowood	Mississippi
United States	JPS Health Network	Fort Worth	Texas
United States	CBH Health	Gaithersburg	Maryland
United States	Collaborative Neuroscience Network, Inc.	Garden Grove	California
United States	Pillar Clinical Research LLC	Garland	Texas
United States	California Clinical Trials	Glendale	California
United States	Baylor College of Medicine	Houston	Texas
United States	University Hills Clinical Research	Irving	Texas
United States	Innovative Clinical Research, Inc.	Lauderhill	Florida
United States	Lifestream Behavioral Center	Leesburg	Florida
United States	Synergy San Diego	Lemon Grove	California
United States	Accel Research Sites - Maitland - ERN - PPDS	Maitland	Florida
United States	Advanced Research Institute of Miami	Miami	Florida
United States	Premier Clinical Research Institute - Miami - BTC - PPDS	Miami	Florida
United States	The Solace Center	Missouri City	Texas
United States	Catalina Research Institute LLC - MRA	Montclair	California
United States	Yale School of Medicine - CT Mental Health Center (CMHC) - Schizophrenia Research Clinic	New Haven	Connecticut
United States	Manhattan Psychiatric Center; Psychopharmacology Research Unit	New York	New York
United States	New York State Psychiatric Institute	New York	New York
United States	Health Synergy Clinical Research	Okeechobee	Florida
United States	ASCLEPES Research Centers	Panorama City	California
United States	@ Health Texas	Richmond	Texas
United States	Psychiatry & Behavioral Center	Richmond	Texas
United States	CITrials, Inc.	Riverside	California
United States	Millennium Psychiatric Associates, LLC	Saint Louis	Missouri
United States	Psych Care Consultants Research	Saint Louis	Missouri
United States	California Neuropsychopharmacology Clinical Research Institute, LLC	San Diego	California
United States	Stanford University School of Medicine	Stanford	California
United States	Collaborative Neuroscience Network Inc.	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Japan,  Spain,  Ukraine, 

Outcome

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