A Study of RO4917838 in Participants With Persistent, Predominant Negative Symptoms of Schizophrenia (NN25310)

A Phase III, Multi-Center, Randomized, 24 Week, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate Efficacy and Safety of RO4917838 in Stable Patients With Persistent, Predominant Negative Symptoms of Schizophrenia Treated With Antipsychotics Followed by a 28 Week, Double-Blind Treatment Period

This multi-center, randomized, double-blind, parallel-group, placebo-controlled study will evaluate the efficacy and safety of RO4917838 in participants with persistent, predominant negative symptoms of schizophrenia. Participants, on stable treatment with antipsychotics, will be randomized to receive daily oral doses of RO4917838 or matching placebo for 56 weeks (treatment period 1 of 24 weeks and treatment period 2 of 32 weeks), followed by an optional treatment extension for up to 3 years. After 52 weeks, participants who were originally randomized to an active treatment will be randomly assigned to receive either placebo or continue on the originally assigned study treatment for 4 weeks washout period (Week 52 to Week 56) for the assessment of potential withdrawal effects in a blinded manner using participants staying on active treatment as a control. Participants initially randomized to placebo will remain on placebo. After 56 weeks, participants who were switched to placebo in the washout period will return to their blinded, active treatment arm.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: RO4917838; Drug: Antipshychotics (Standard of Care); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 629
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1425
    • Centro SERES
  • Buenos Aires, Argentina, C1425AHQ
    • Fundacion para el Estudio y Tratamiento des las Enfi Mentales
  • Caba, Argentina, C1022AAO
    • Mulieris
  • Ciudad Autonoma Bs As, Argentina, 1117
    • Facene Fund.Argentina Contra Enferm.Neur.Del Envejecimiento
  • Ciudad Autonoma Bs As, Argentina, 1405
    • Instituto Nacional de Psicopatologia
  • Ciudad de Mendoza, Argentina, 5500
    • Resolution Psicopharmacology Research Institute
  • Cordoba, Argentina, 5003
    • Instituto DAMIC - Fundacion Rusculleda
  • Cordoba, Argentina, X5009BIN
    • Sanatorio Prof.Leon.S.Morra S.A
  • La Plata, Argentina, 1900
    • Instituto de Neurociencias San Agustín S.A.
  • Mendoza, Argentina, 5500
    • Centro de Psiquiatria Biologica Professor Julio J. Herrera; Psiquiatria
  • Mendoza, Argentina
    • Centro de Asistencia e Investigación en Neurociencias
  • Rosario, Argentina, S2000QJI
    • CIAP - Centro de Investigacion y Asistencia en Psiquiatria
  • Santiago del Estero, Argentina, 4200
    • Centro de Investigacion Clinica Farmacologica en Psiquiatria
• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital; Department of Psychiatry
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre-Clayton Campus; School of Psychology and Psychiatry
    • Frankston, Victoria, Australia, 3199
      • Frankston Hospital; Mental Health Service
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital; Monash Alfred Psychiatry Research Centre (MAP-RC)
• Colombia
  • Barranquilla, Colombia
    • Centro de Investigaciones y Proyectos en Neurociencias CIPNA
  • Bello, Colombia
    • E.S.E. Hospital Mental de Antioquia
  • Bogota, Colombia
    • Centro de Investigaciones del Sistema Nervioso Limitada - Gr
• Finland
  • Kuopio, Finland, 70100
    • Privater
• France
  • Caen, France, 14033
    • Centre Hospitalier Universitaire Caen; Pôle Psychiatrie - Addictologie
  • Clermont-ferrand, France, 63000
    • CHU Gabriel Montpied; Service de Psychiatrie
  • Dole, France, 39100
    • Centre Hospitalier Specialise du Jura
  • Elancourt, France, 78990
    • Cabinet Médical Ambroise Paré
  • Marseille, France, 13005
    • Hôpital de la Conception; Pôle Psychiatrique Centre
  • Strasbourg, France, 67091
    • CHU Strasbourg Nouvel Hôpital Civil;Service de Psychiatrie I
  • Toulon, France, 83000
    • Hopital Chalucet; Unite de Psychiatrie
• Hungary
  • Balassagyarmat, Hungary, 2660
    • Dr. Kenessey Albert Hospital; Psychiatry I.
  • Budapest, Hungary, 1135
    • UNO Medical Trials Kft.
  • Budapest, Hungary, 1032
    • Fov.Onk.Szt Janos Korh. E-Budai Egyesitett Korhazai; Pszichiatriaci rehabilitacio
  • Budapest, Hungary, 1082
    • Semmelweis Egyetem AOK; Pszichiatriai es Pszichoterapias Klinika
  • Budapest, Hungary, 1135
    • Fovarosi Onkormanyzat Nyiro Gyula Korhaza; Pszichatria II
  • Budapest, Hungary, 1135
    • Fovarosi Onkormanyzat Nyiro Gyula Korhaza; Pszichiatria I.
  • Gyor, Hungary, 9024
    • Petz Aladar Megyei Oktato Korhaz; Pszichiatria I.
  • Gyula, Hungary, 5703
    • Békés Megyei Pándy Kálmán Kórház; Onkologiai tanszek
• India
  • Ahmedabad, India, 380006
    • Samvedna Hospitals; Samvedana Psychiatry and Sex Therapy Hospital
  • Ahmedabad, India, 380008
    • Sneh Clinic
  • Ahmedabad, India, 380015
    • Gujarat Institute of Psychological Research (GIPS)
  • Jaipur, India, 302017
    • Mental Health Care & Research
  • Jaipur, India, 302021
    • R. K.Yadav Memorial Mental Health & De-Addiction Hospital
  • Kalyan, India, 421301
    • Manav Neuropsychiatric Hospital Pvt. Ltd.
  • Mangalore, India, 575001
    • Kasturba Medical College & Hospital
  • Mangalore, India, 575018
    • K. S. Hegde Medical Academy
  • Pune, India, 411030
    • Poona hospital and research centre
  • Vadodara, India, 390001
    • Brij Psychiatry Hospital & Muskaan Research Centre; Maanav Health Foundation
• Korea, Republic of
  • Busan, Korea, Republic of, 47392
    • Inje University Busan Paik Hospital
  • Gwangju, Korea, Republic of, 61469
    • Chonnam National University Hospital
  • Gyeonggi-do, Korea, Republic of, 15355
    • Korea University Ansan Hospital
  • Incheon, Korea, Republic of, 22332
    • Inha University Hospital
  • Incheon, Korea, Republic of, 405-760
    • Gil Hospital. Gachon University
  • Jeollabuk-do, Korea, Republic of, 561-712
    • Chonbuk National Uni Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 150-713
    • The Catholic University of Korea St.Mary's Hospital
• Mexico
  • Mexico, Mexico, 05300
    • Arete Proycectos y Administracion S.C
  • Monterrey, Mexico, 64000
    • Centro de Investigacion Medica S.C; Hospital Santa Cecilia de Monterrey S.A. de C.V.
  • Monterrey, Mexico, 64060
    • Medikalink
  • Monterrey, Mexico, 64710
    • Instituto de informacion e investigacion en salud mental AC
  • San Luis Potosi, Mexico, 72818
    • Hospital Lomas de San Luis Internacional
• Romania
  • Arad, Romania, 310022
    • Spitalul Clinic Judetean Arad; Departamentul de Psihiatrie
  • Bucuresti, Romania, 010825
    • Spit Univ Urgenta Militar Dr. Carol Davila; Sectia Psihiatrie
  • Bucuresti, Romania, 041914
    • Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia; Clinical III Psihiatrie
  • Bucuresti, Romania, 041914
    • Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia; Comunitara si Reintegrare Psihosociala
  • Bucuresti, Romania, 041914
    • Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia; Sectia Clinica XIII Psihiatrie
  • Cluj-Napoca, Romania, 400012
    • Spitalul Clinic Judetean de Urgenta Cluj; Sectia Clinica de Psihiatrie III
  • Lasi, Romania, 700282
    • Spitalul Universitar de Psihiatrie Socola
  • Oradea, Romania, 410154
    • Spitalul Clinic Municipal Dr. Gavril Curteanu; Sectia Clinica Psihiatrie I
  • Sibiu, Romania, 550082
    • Spitalul de Psihiatrie Dr. Gh. Preda Sibiu;CSM Adulti Sibiu
  • Targouiste, Romania, 130081
    • Cabinet Medical S.C. Lorentina 2102 S.R.L.; Psihiatrie
• Russian Federation
  • Kemerovo, Russian Federation, 650036
    • Kemerovo Regional Clinical Psychiatric Hospital
  • Lipetsk, Russian Federation, 399313
    • GUZ Lipetsk Regional psychoneurological Hospital #1; Dispansary Department
  • Moscow, Russian Federation, 115522
    • Institution of RAMS (Mental Health Research Center of RAMS)
  • Moscow, Russian Federation, 127083
    • Central Moscow Regional Clinical Psychiatric Hospital
  • Moscow, Russian Federation, 107076
    • Scientifically Research Institute of Psychiatry of Ministry of Health of the Russian Federation
  • Moscow, Russian Federation, 117995
    • Federal State Institution Moscow SRI of Psychiatry of Minzdravsocrazvitia
  • Moscow Region, Russian Federation, 142601
    • Moscow Region Psychiatric Hospital #5
  • Nizhny Novgorod, Russian Federation, 603155
    • City Clinical Psychiatry Hospital #1
  • Saint Petersburg, Russian Federation, 194044
    • Military Medical Academy
  • Samara, Russian Federation, 443016
    • Samara Psychiatric Hospital
  • Sartatov, Russian Federation, 410028
    • Mhi City Clinical Hospital #2 Named After v.i. Razumousky
  • St Petersbourg, Russian Federation, 190005
    • St. Petersburg State Healthcare Institution
  • St Petersburg, Russian Federation, 193167
    • St. Petersburg GUZ City Psychiatric Hospital #6
  • St Petersburg, Russian Federation, 197341
    • St. Petersburg State Healthcare Institution "City Mental Hospital #3; I.I. Skvortsov-Stepanov
  • St. Petersburg, Russian Federation, 190121
    • City Psychiatric Hospital #2 of St. Nikolay Chudotvorets
  • St. Petersburg, Russian Federation, 192019
    • Saint Petersburg Psychoneurological Research Institute of Roszdrav n.a. Bekhterev
  • Talagi, Russian Federation, 163530
    • Arkhangelsk Regional Clinical Psychiatric Hospital
  • Tomsk, Russian Federation, 634014
    • Tomsk Clinical Psychiatric Hospital
• Sweden
  • Malmö, Sweden, 21135
    • Integrerad Närsjukvård i Malmö
  • Stockholm, Sweden, 14186
    • Karolinska Universitetssjukhuset Huddinge, Psykiatri Sydväst
  • Stockholm, Sweden, 18288
    • Danderyds Sjukhus AB; PRIMA Vuxenpsykiatri
  • Uppsala, Sweden, 75185
    • Akademiska Sjukhuset; Psykosvård och rättspsykiatrisk vård
• United Kingdom
  • Edinburgh, United Kingdom, EH10 5HF
    • Royal Edinburgh Hospital; Psychiatry
  • London, United Kingdom, SE5-8AF
    • Institute of Pyschiatry
  • Oxford, United Kingdom, OX3 7JX
    • Wareneford Hospital
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72201
      • K&S Professional Research Services LLC
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center Inc.
    • Cerritos, California, United States, 90703
      • Comprehensive Clinical Development- Cerritos CA
    • Downey, California, United States, 90241
      • Diligent Clinical Trials Inc
    • La Palma, California, United States, 90623
      • Care Research Center
    • Pasadena, California, United States, 91106
      • Pasadena Research Institute
    • Pico Rivera, California, United States, 90660
      • CNRI - Los Angeles, LLC
  • Florida
    • Miami, Florida, United States, 33126
      • Pharmax Research Clinic Inc.
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Northwest Behavioral Research Center
  • Illinois
    • Oak Brook, Illinois, United States, 60523
      • American Medical Research, Inc
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa College of Medicine; Psychiatry Research
  • Maryland
    • Glen Burnie, Maryland, United States, 21061
      • Clinical Insights, Inc.
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • St Louis Clinical Trials
  • New Jersey
    • Toms River, New Jersey, United States, 08775
      • Ocean Rheumatology
    • Willingboro, New Jersey, United States, 08046
      • CRI Worldwide LLC
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
      • Raymond G. Murphy VA Medical Center
  • New York
    • Brooklyn, New York, United States, 11201
      • Behavioral Medical Research of Brooklyn
    • Fresh Meadows, New York, United States, 11366
      • Comprehensive Neuroscience
  • North Carolina
    • Raleigh, North Carolina, United States, 27603
      • North Carolina Psychiatric Research Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • UC Health Clinical Trials Office
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19131
      • Belmont Center for Comprehensive Treatment; Research
  • Texas
    • Bellaire, Texas, United States, 77401
      • Claghorn-Lesem Research Clinic, Inc.
    • Dallas, Texas, United States, 75231
      • FutureSearch Clinical Trials, LP
    • Dallas, Texas, United States, 75243
      • Pillar Clinical Research LLC
    • The Woodlands, Texas, United States, 77381
      • Family Psychiatry of the Woodlands P.A.
  • Washington
    • Bothell, Washington, United States, 98011
      • Pacific Institute of Medical Sciences
    • Kirkland, Washington, United States, 98033
      • Eastside Therapeutic Resource

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of schizophrenia of paranoid, disorganized, residual, undifferentiated or catatonic subtype
• Predominant negative symptoms
• With the exception of clozapine, participants are on any of the available marketed atypical or typical antipsychotics (treatment with a maximum of two antipsychotics)

Exclusion Criteria:

• Evidence that participant has clinically significant, uncontrolled and unstable disorder (e.g. cardiovascular, renal, hepatic disorder)
• Body Mass Index (BMI) of less than (<) 17 or greater than (>) 40 kilograms per meter square (kg/m^2)
• Depressive symptoms, defined as a score of 9 or greater on the Calgary Depression Rating Scale for Schizophrenia (CDSS)
• A severity score of 3 or greater on the Parkinsonism item of the Exrapyramidal Symptoms Rating Scale-Abbreviated (ESRS-A) (Clinical Global Impression, Parkinsonism)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RO4917838 20 milligrams (mg); Participants, on stable antipsychotics, will receive RO4917838 orally at 20 mg once daily (QD) up to 56 weeks followed by an optional treatment extension for up to 3 years.	Drug: RO4917838; RO4917838 will be administered orally at 20 or 10 mg QD for 56 weeks.; Drug: Antipshychotics (Standard of Care); Participants will continue to receive their stable antipshychotic as standard of care based on their prescription up to Week 56.
Experimental: RO4917838 10 mg; Participants, on stable antipsychotics, will receive RO4917838 orally at 10 mg QD up to 56 weeks followed by an optional treatment extension for up to 3 years.	Drug: RO4917838; RO4917838 will be administered orally at 20 or 10 mg QD for 56 weeks.; Drug: Antipshychotics (Standard of Care); Participants will continue to receive their stable antipshychotic as standard of care based on their prescription up to Week 56.
Placebo Comparator: Placebo; Participants, on stable antipsychotics, will receive RO4917838 matching placebo orally QD up to 56 weeks.	Drug: Antipshychotics (Standard of Care); Participants will continue to receive their stable antipshychotic as standard of care based on their prescription up to Week 56.; Drug: Placebo; Placebo will be administered orally QD for 56 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in the Positive and Negative Symptoms Scales (PANSS) Negative Symptoms Factor Score at Week 24 (All-Participant Population)	Baseline, Week 24
Percentage of Participants With Adverse Events (All-Participant Population)	Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in the PANSS Negative Symptoms Factor Score at Week 24 (Complement Factor H Related Protein 1 High [CFHR1-High] Subgroup Population)	Baseline, Week 24
Change From Baseline in the Personal and Social Performance (PSP) Total Score at Week 24 (All-Participant Population)	Baseline, Week 24
Change From Baseline in the PSP Total Score at Week 24 (CFHR1-High Subgroup Population)	Baseline, Week 24
Change From Baseline in the PANSS Total Score at Week 24 (All-Participant Population)	Baseline, Week 24
Change From Baseline in the PANSS Total Score at Week 24 (CFHR1-High Subgroup Population)	Baseline, Week 24
Change From Baseline in the PANSS Factor Score at Week 24 (All-Participant Population)	Baseline, Week 24
Change From Baseline in the PANSS Factor Score at Week 24 (CFHR1-High Subgroup Population)	Baseline, Week 24
Change From Baseline in the PANSS Subscale Scores at Week 24 (All-Participant Population)	Baseline, Week 24
Change From Baseline in the PANSS Subscale Scores at Week 24 (CFHR1-High Subgroup Population)	Baseline, Week 24
Percentage of Participants Who Have at least 20 Percent (%) Improvement From Baseline in the PANSS Negative Symptom Factor Score at Week 24 (All-Participant Population)	Baseline, Week 24
Percentage of Participants Who Have at least 20% Improvement From Baseline in the PANSS Negative Symptom Factor Score at Week 24 (CFHR1-High Subgroup Population)	Baseline, Week 24
Percentage of Participants Who Have at least 20% Improvement From Baseline in the PANSS Negative Symptom Factor Score for Two out of Three Assessments During 24 Weeks (All-Participant Population)	Baseline up to Week 24
Percentage of Participants Who Have at least 20% Improvement From Baseline in the PANSS Negative Symptom Factor Score for Two out of Three Assessments During 24 Weeks (CFHR1-High Subgroup Population)	Baseline up to Week 24
Percentage of Participants With Improvement From Baseline in the Overall Clinical Status Based on Clinical Global Impression - Improvement (CGI-I) Score (All-Participant Population)	Baseline, Week 24
Percentage of Participants With Improvement From Baseline in the Overall Clinical Status Based on CGI-I Score (CFHR1 Subgroup Population)	Baseline, Week 24
Percentage of Participants With Improvement From Baseline in the Overall Clinical Status Based on CGI-I Score for Two out of Three Assessments During 24 Weeks (All-Participant Population)	Baseline up to Week 24
Percentage of Participants With Improvement From Baseline in the Overall Clinical Status Based on CGI-I Score for Two out of Three Assessments During 24 Weeks (CFHR1 Subgroup Population)	Baseline up to Week 24
Percentage of Participants With Improvement From Baseline in the Negative Symptoms Based on CGI-I Negative Symptoms Score (All-Participant Population)	Baseline, Week 24
Percentage of Participants With Improvement From Baseline in the Negative Symptoms Based on CGI-I Negative Symptoms Score (CFHR1 Subgroup Population)	Baseline, Week 24
Percentage of Participants With Improvement From Baseline in the Negative Symptoms Based on CGI-I Negative Symptoms Score for Two out of Three Assessments During 24 Weeks (All-Participant Population)	Baseline up to Week 24
Percentage of Participants With Improvement From Baseline in the Negative Symptoms Based on CGI-I Negative Symptoms Score for Two out of Three Assessments During 24 Weeks (CFHR1 Subgroup Population)	Baseline up to Week 24
Percentage of Participants Who Have at least 20% Improvement From Baseline in the PANSS Negative Symptom Factor Score at Week 24 and Improvement in the Negative Symptoms Based on CGI-I Negative Symptoms Score (All-Participant Population)	Baseline, Week 24
Percentage of Participants Who Have at least 20% Improvement From Baseline in the PANSS Negative Symptom Factor Score at Week 24 and Improvement in the Negative Symptoms Based on CGI-I Negative Symptoms Score (CFHR1 Subgroup Population)	Baseline, Week 24
Change From Baseline in Severity of Illness Based on Clinical Global Impression - Severity (CGI-S) Overall Score (All-Participant Population)	Baseline, Week 24
Change From Baseline in Severity of Illness Based on CGI-S Overall Score (CFHR1 Subgroup Population)	Baseline, Week 24
Change From Baseline in Severity of Illness Based on CGI-S Negative Symptoms Score (All-Participant Population)	Baseline, Week 24
Change From Baseline in Severity of Illness Based on CGI-S Negative Symptoms Score (CFHR1 Subgroup Population)	Baseline, Week 24

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Georgiades A, Davis VG, Atkins AS, Khan A, Walker TW, Loebel A, Haig G, Hilt DC, Dunayevich E, Umbricht D, Sand M, Keefe RSE. Psychometric characteristics of the MATRICS Consensus Cognitive Battery in a large pooled cohort of stable schizophrenia patients. Schizophr Res. 2017 Dec;190:172-179. doi: 10.1016/j.schres.2017.03.040. Epub 2017 Apr 20.
• Bugarski-Kirola D, Blaettler T, Arango C, Fleischhacker WW, Garibaldi G, Wang A, Dixon M, Bressan RA, Nasrallah H, Lawrie S, Napieralski J, Ochi-Lohmann T, Reid C, Marder SR. Bitopertin in Negative Symptoms of Schizophrenia-Results From the Phase III FlashLyte and DayLyte Studies. Biol Psychiatry. 2017 Jul 1;82(1):8-16. doi: 10.1016/j.biopsych.2016.11.014. Epub 2016 Dec 15.

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2010
• Primary Completion (Actual): May 26, 2014
• Study Completion (Actual): May 26, 2014

Study Registration Dates

• First Submitted: August 30, 2010
• First Submitted That Met QC Criteria: August 30, 2010
• First Posted (Estimate): September 1, 2010

Study Record Updates

• Last Update Posted (Actual): June 26, 2017
• Last Update Submitted That Met QC Criteria: June 23, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: NN25310; 2010-020370-42 (EudraCT Number)