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

NCT03669640 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: BP40283
• Study Type: interventional
• Target: 131
• Locations: 4 countries
• Sites: 45

Brief Summary

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

Conditions

Schizophrenia, Schizoaffective Disorder

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Clinical Global Impression Severity (CGI-S) Overall Scores

  Baseline to week 12

• CGI-S Negative Symptoms (NS) Scores

  Baseline to week 12

• Clinical Global Impression - Improvement (CGI-I) Overall Scores

  Up to Week 12 (Day 84)

• CGI-I Negative Symptoms Scores

  Up to Week 12 (Day 84)

• Positive and Negative Syndrome Scale (PANSS) Total Scores

  Baseline to week 12

Study Arms (2)

Part A: Monotherapy

EXPERIMENTAL

Participants will receive RO6889450 or a dose-matched placebo. NOTE: Part A has completed enrollment.

Drug: RO6889450; Drug: Placebo

Part B: Add-On Therapy

EXPERIMENTAL

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; Drug: Placebo

Interventions

RO6889450 DRUG

Participants will receive a once-daily, oral dose of RO6889450 for 12 weeks.

Part A: Monotherapy; Part B: Add-On Therapy

Placebo DRUG

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

Part A: Monotherapy; Part B: Add-On Therapy

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (45)

CITrials, Inc.

Bellflower, California, 90706, United States

Location

Collaborative Neuroscience Network, Inc.

Garden Grove, California, 92845, United States

Location

California Clinical Trials

Glendale, California, 91206, United States

Location

Synergy San Diego

Lemon Grove, California, 91945, United States

Location

Catalina Research Institute LLC - MRA

Montclair, California, 91763, United States

Location

CITrials, Inc.

Riverside, California, 92506, United States

Location

California Neuropsychopharmacology Clinical Research Institute, LLC

San Diego, California, 92102, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Collaborative Neuroscience Network Inc.

Torrance, California, 90502, United States

Location

Yale School of Medicine - CT Mental Health Center (CMHC) - Schizophrenia Research Clinic

New Haven, Connecticut, 06519, United States

Location

Innovative Clinical Research, Inc.

Lauderhill, Florida, 33319, United States

Location

Lifestream Behavioral Center

Leesburg, Florida, 34748, United States

Location

Advanced Research Institute of Miami

Miami, Florida, 33135, United States

Location

Health Synergy Clinical Research

Okeechobee, Florida, 34972, United States

Location

Emory University

Atlanta, Georgia, 30329, United States

Location

Northwestern University

Chicago, Illinois, 60611-2908, United States

Location

CBH Health

Gaithersburg, Maryland, 20877, United States

Location

Precise Research Centers

Flowood, Mississippi, 39232, United States

Location

Psych Care Consultants Research

St Louis, Missouri, 63128, United States

Location

Millennium Psychiatric Associates, LLC

St Louis, Missouri, 63132, United States

Location

Manhattan Psychiatric Center; Psychopharmacology Research Unit

New York, New York, 10035, United States

Location

JPS Health Network

Fort Worth, Texas, 76104, United States

Location

Pillar Clinical Research LLC

Garland, Texas, 75042, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University Hills Clinical Research

Irving, Texas, 75062, United States

Location

The Solace Center

Missouri City, Texas, 77459, United States

Location

Psychiatry & Behavioral Center

Richmond, Texas, 77406, United States

Location

@ Health Texas

Richmond, Texas, 77407, United States

Location

Kohnodai Hp., National Center for Global Health and Medicine

Chiba, 272-8516, Japan

Location

National Hospital Organization Ryukyu Hospital

Kunigami, 904-1201, Japan

Location

National Center of Neurology and Psychiatry

Tokyo, 187-8551, Japan

Location

Seishinkai Okehazama Hospital Fujita Kokoro Care Center

Toyoake, 470-1168, Japan

Location

Hiyoshi Hospital

Yokohama, 223-0062, Japan

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

Location

C.H. Regional Reina Sofia - PPDS

Córdoba, 14004, Spain

Location

Hosp Univ Fundacion Alcorcon

Madrid, 28922, Spain

Location

Complejo Asistencial Universitario de Salamanca ? H. Clinico

Salamanca, 37007, Spain

Location

CNCE Regional Clinical Psychiatric Hospital of Kirovohrad Regional Council

Nove, Katerynoslav Governorate, 25491, Ukraine

Location

Communal Non-Commercial Enterprise of Kharkiv RC Regional clinical psychiatric hospital #3

Kharkiv, Kharkiv Governorate, 61068, Ukraine

Location

Public NPE Kherson Regional Institution of Mental Care of Kherson RC

Kherson, Kherson Governorate, 73488, Ukraine

Location

Municipal Non-Commercial Enterprise Odesa RMC for Mental Health of Odessa Regional Council

Odesa, Kherson Governorate, 65006, Ukraine

Location

ME Dnipropetrovsk Regional Clinical Hospital n.a. I.I Mechnykov Dnipropetrovsk Regional Council

Dnipro, KIEV Governorate, 49005, Ukraine

Location

Zakarpattia Regional Clinical Hospital n.a. Andrii Novak

Uzhhorod, KIEV Governorate, 88000, Ukraine

Location

Communal NPE Vinnytsia Reg. Clin. Psychoneurolog. Hosp. n.a. O.I. Yushchenko of Vinnytsia RC

Vinnytsia, Podolia Governorate, 21037, Ukraine

Location

Related Publications (1)

• Halff EF, Rutigliano G, Garcia-Hidalgo A, Howes OD. Trace amine-associated receptor 1 (TAAR1) agonism as a new treatment strategy for schizophrenia and related disorders. Trends Neurosci. 2023 Jan;46(1):60-74. doi: 10.1016/j.tins.2022.10.010. Epub 2022 Nov 8.

  PMID: 36369028 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Medical Communications
• Organization: F. Hoffmann-La Roche

genentech@druginfo.com

1-800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2018
• First Posted: September 13, 2018
• Study Start: December 4, 2018
• Primary Completion: March 12, 2023
• Study Completion: March 12, 2023
• Last Updated: August 12, 2024
• Results First Posted: August 12, 2024

Record last verified: 2024-08

Locations

US (28); JP (5); ES (5); UA (7)