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

Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01192867
• Other study ID #: NN25310
• Secondary ID: 2010-020370-42
• Status: Completed
• Phase: Phase 3
• First received: August 30, 2010
• Last updated: June 23, 2017
• Start date: December 11, 2010
• Est. completion date: May 26, 2014

Study information

• Verified date: June 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 629
• Est. completion date: May 26, 2014
• Est. primary completion date: May 26, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Placebo
Placebo will be administered orally QD for 56 weeks
• RO4917838
RO4917838 will be administered orally at 20 or 10 mg QD for 56 weeks.
• Antipshychotics (Standard of Care)
Participants will continue to receive their stable antipshychotic as standard of care based on their prescription up to Week 56.

Locations

Country	Name	City	State
Argentina	Centro SERES	Buenos Aires
Argentina	Fundacion para el Estudio y Tratamiento des las Enfi Mentales	Buenos Aires
Argentina	Mulieris	Caba
Argentina	Facene Fund.Argentina Contra Enferm.Neur.Del Envejecimiento	Ciudad Autonoma Bs As
Argentina	Instituto Nacional de Psicopatologia	Ciudad Autonoma Bs As
Argentina	Resolution Psicopharmacology Research Institute	Ciudad de Mendoza
Argentina	Instituto DAMIC - Fundación Rusculleda	Cordoba
Argentina	Sanatorio Prof.Leon.S.Morra S.A	Cordoba
Argentina	Instituto de Neurociencias San Agustín S.A.	La Plata
Argentina	Centro de Asistencia e Investigación en Neurociencias	Mendoza
Argentina	Centro de Psiquiatria Biologica Professor Julio J. Herrera; Psiquiatria	Mendoza
Argentina	CIAP - Centro de Investigacion y Asistencia en Psiquiatria	Rosario
Argentina	Centro de Investigacion Clinica Farmacologica en Psiquiatria	Santiago del Estero
Australia	Monash Medical Centre-Clayton Campus; School of Psychology and Psychiatry	Clayton	Victoria
Australia	Frankston Hospital; Mental Health Service	Frankston	Victoria
Australia	The Alfred Hospital; Monash Alfred Psychiatry Research Centre (MAP-RC)	Melbourne	Victoria
Australia	Westmead Hospital; Department of Psychiatry	Westmead	New South Wales
Colombia	Centro de Investigaciones y Proyectos en Neurociencias CIPNA	Barranquilla
Colombia	E.S.E. Hospital Mental de Antioquia	Bello
Colombia	Centro de Investigaciones del Sistema Nervioso Limitada - Gr	Bogota
Finland	Privater	Kuopio
France	Centre Hospitalier Universitaire Caen; Pôle Psychiatrie - Addictologie	Caen
France	CHU Gabriel Montpied; Service de Psychiatrie	Clermont-ferrand
France	Centre Hospitalier Specialise du Jura	Dole
France	Cabinet Médical Ambroise Paré	Elancourt
France	Hôpital de la Conception; Pôle Psychiatrique Centre	Marseille
France	CHU Strasbourg Nouvel Hôpital Civil;Service de Psychiatrie I	Strasbourg
France	Hopital Chalucet; Unite de Psychiatrie	Toulon
Hungary	Dr. Kenessey Albert Hospital; Psychiatry I.	Balassagyarmat
Hungary	Fov.Onk.Szt Janos Korh. E-Budai Egyesitett Korhazai; Pszichiatriaci rehabilitacio	Budapest
Hungary	Fovarosi Onkormanyzat Nyiro Gyula Korhaza; Pszichatria II	Budapest
Hungary	Fovarosi Onkormanyzat Nyiro Gyula Korhaza; Pszichiatria I.	Budapest
Hungary	Semmelweis Egyetem AOK; Pszichiatriai es Pszichoterapias Klinika	Budapest
Hungary	UNO Medical Trials Kft.	Budapest
Hungary	Petz Aladar Megyei Oktato Korhaz; Pszichiatria I.	Gyor
Hungary	Békés Megyei Pándy Kálmán Kórház; Onkologiai tanszek	Gyula
India	Gujarat Institute of Psychological Research (GIPS)	Ahmedabad
India	Samvedna Hospitals; Samvedana Psychiatry and Sex Therapy Hospital	Ahmedabad
India	Sneh Clinic	Ahmedabad
India	Mental Health Care & Research	Jaipur
India	R. K.Yadav Memorial Mental Health & De-Addiction Hospital	Jaipur
India	Manav Neuropsychiatric Hospital Pvt. Ltd.	Kalyan
India	K. S. Hegde Medical Academy	Mangalore
India	Kasturba Medical College & Hospital	Mangalore
India	Poona Hospital and Research Centre	Pune
India	Brij Psychiatry Hospital & Muskaan Research Centre; Maanav Health Foundation	Vadodara
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Korea University Ansan Hospital	Gyeonggi-do
Korea, Republic of	Gil Hospital. Gachon University	Incheon
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Chonbuk National Uni Hospital	Jeollabuk-do
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	The Catholic University of Korea St.Mary's Hospital	Seoul
Mexico	Arete Proycectos y Administracion S.C	Mexico
Mexico	Centro de Investigacion Medica S.C; Hospital Santa Cecilia de Monterrey S.A. de C.V.	Monterrey
Mexico	Instituto de informacion e investigacion en salud mental AC	Monterrey
Mexico	Medikalink	Monterrey
Mexico	Hospital Lomas de San Luis Internacional	San Luis Potosi
Romania	Spitalul Clinic Judetean Arad; Departamentul de Psihiatrie	Arad
Romania	Spit Univ Urgenta Militar Dr. Carol Davila; Sectia Psihiatrie	Bucuresti
Romania	Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia; Clinical III Psihiatrie	Bucuresti
Romania	Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia; Comunitara si Reintegrare Psihosociala	Bucuresti
Romania	Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia; Sectia Clinica XIII Psihiatrie	Bucuresti
Romania	Spitalul Clinic Judetean de Urgenta Cluj; Sectia Clinica de Psihiatrie III	Cluj-Napoca
Romania	Spitalul Universitar de Psihiatrie Socola	Lasi
Romania	Spitalul Clinic Municipal Dr. Gavril Curteanu; Sectia Clinica Psihiatrie I	Oradea
Romania	Spitalul de Psihiatrie Dr. Gh. Preda Sibiu;CSM Adulti Sibiu	Sibiu
Romania	Cabinet Medical S.C. Lorentina 2102 S.R.L.; Psihiatrie	Targouiste
Russian Federation	Kemerovo Regional Clinical Psychiatric Hospital	Kemerovo
Russian Federation	GUZ Lipetsk Regional psychoneurological Hospital #1; Dispansary Department	Lipetsk
Russian Federation	Central Moscow Regional Clinical Psychiatric Hospital	Moscow
Russian Federation	Federal State Institution Moscow SRI of Psychiatry of Minzdravsocrazvitia	Moscow
Russian Federation	Institution of RAMS (Mental Health Research Center of RAMS)	Moscow
Russian Federation	Scientifically Research Institute of Psychiatry of Ministry of Health of the Russian Federation	Moscow
Russian Federation	Moscow Region Psychiatric Hospital #5	Moscow Region
Russian Federation	City Clinical Psychiatry Hospital #1	Nizhny Novgorod
Russian Federation	Military Medical Academy	Saint Petersburg
Russian Federation	Samara Psychiatric Hospital	Samara
Russian Federation	Mhi City Clinical Hospital #2 Named After v.i. Razumousky	Sartatov
Russian Federation	St. Petersburg State Healthcare Institution	St Petersbourg
Russian Federation	St. Petersburg GUZ City Psychiatric Hospital #6	St Petersburg
Russian Federation	St. Petersburg State Healthcare Institution "City Mental Hospital #3; I.I. Skvortsov-Stepanov	St Petersburg
Russian Federation	City Psychiatric Hospital #2 of St. Nikolay Chudotvorets	St. Petersburg
Russian Federation	Saint Petersburg Psychoneurological Research Institute of Roszdrav n.a. Bekhterev	St. Petersburg
Russian Federation	Arkhangelsk Regional Clinical Psychiatric Hospital	Talagi
Russian Federation	Tomsk Clinical Psychiatric Hospital	Tomsk
Sweden	Integrerad Närsjukvård i Malmö	Malmö
Sweden	Danderyds Sjukhus AB; PRIMA Vuxenpsykiatri	Stockholm
Sweden	Karolinska Universitetssjukhuset Huddinge, Psykiatri Sydväst	Stockholm
Sweden	Akademiska Sjukhuset; Psykosvård och rättspsykiatrisk vård	Uppsala
United Kingdom	Royal Edinburgh Hospital; Psychiatry	Edinburgh
United Kingdom	Institute of Pyschiatry	London
United Kingdom	Wareneford Hospital	Oxford
United States	Raymond G. Murphy VA Medical Center	Albuquerque	New Mexico
United States	Advanced Research Center Inc.	Anaheim	California
United States	Claghorn-Lesem Research Clinic, Inc.	Bellaire	Texas
United States	Pacific Institute of Medical Sciences	Bothell	Washington
United States	Behavioral Medical Research of Brooklyn	Brooklyn	New York
United States	Comprehensive Clinical Development- Cerritos CA	Cerritos	California
United States	UC Health Clinical Trials Office	Cincinnati	Ohio
United States	FutureSearch Clinical Trials, LP	Dallas	Texas
United States	Pillar Clinical Research LLC	Dallas	Texas
United States	Diligent Clinical Trials Inc	Downey	California
United States	Comprehensive NeuroScience	Fresh Meadows	New York
United States	Clinical Insights, Inc.	Glen Burnie	Maryland
United States	University of Iowa College of Medicine; Psychiatry Research	Iowa City	Iowa
United States	Eastside Therapeutic Resource	Kirkland	Washington
United States	Care Research Center	La Palma	California
United States	K&S Professional Research Services LLC	Little Rock	Arkansas
United States	Northwest Behavioral Research Center	Marietta	Georgia
United States	Pharmax Research Clinic Inc.	Miami	Florida
United States	American Medical Research, Inc	Oak Brook	Illinois
United States	Pasadena Research Institute	Pasadena	California
United States	Belmont Center for Comprehensive Treatment; Research	Philadelphia	Pennsylvania
United States	CNRI - Los Angeles, LLC	Pico Rivera	California
United States	North Carolina Psychiatric Research Center	Raleigh	North Carolina
United States	St Louis Clinical Trials	Saint Louis	Missouri
United States	Family Psychiatry of the Woodlands P.A.	The Woodlands	Texas
United States	Ocean Rheumatology	Toms River	New Jersey
United States	CRI Worldwide LLC	Willingboro	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Colombia,  Finland,  France,  Hungary,  India,  Korea, Republic of,  Mexico,  Romania,  Russian Federation,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Positive and Negative Symptoms Scales (PANSS) Negative Symptoms Factor Score at Week 24 (All-Participant Population)		Baseline, Week 24
Primary	Percentage of Participants With Adverse Events (All-Participant Population)		Week 24
Secondary	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
Secondary	Change From Baseline in the Personal and Social Performance (PSP) Total Score at Week 24 (All-Participant Population)		Baseline, Week 24
Secondary	Change From Baseline in the PSP Total Score at Week 24 (CFHR1-High Subgroup Population)		Baseline, Week 24
Secondary	Change From Baseline in the PANSS Total Score at Week 24 (All-Participant Population)		Baseline, Week 24
Secondary	Change From Baseline in the PANSS Total Score at Week 24 (CFHR1-High Subgroup Population)		Baseline, Week 24
Secondary	Change From Baseline in the PANSS Factor Score at Week 24 (All-Participant Population)		Baseline, Week 24
Secondary	Change From Baseline in the PANSS Factor Score at Week 24 (CFHR1-High Subgroup Population)		Baseline, Week 24
Secondary	Change From Baseline in the PANSS Subscale Scores at Week 24 (All-Participant Population)		Baseline, Week 24
Secondary	Change From Baseline in the PANSS Subscale Scores at Week 24 (CFHR1-High Subgroup Population)		Baseline, Week 24
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of Participants With Improvement From Baseline in the Overall Clinical Status Based on CGI-I Score (CFHR1 Subgroup Population)		Baseline, Week 24
Secondary	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
Secondary	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
Secondary	Percentage of Participants With Improvement From Baseline in the Negative Symptoms Based on CGI-I Negative Symptoms Score (All-Participant Population)		Baseline, Week 24
Secondary	Percentage of Participants With Improvement From Baseline in the Negative Symptoms Based on CGI-I Negative Symptoms Score (CFHR1 Subgroup Population)		Baseline, Week 24
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change From Baseline in Severity of Illness Based on Clinical Global Impression - Severity (CGI-S) Overall Score (All-Participant Population)		Baseline, Week 24
Secondary	Change From Baseline in Severity of Illness Based on CGI-S Overall Score (CFHR1 Subgroup Population)		Baseline, Week 24
Secondary	Change From Baseline in Severity of Illness Based on CGI-S Negative Symptoms Score (All-Participant Population)		Baseline, Week 24
Secondary	Change From Baseline in Severity of Illness Based on CGI-S Negative Symptoms Score (CFHR1 Subgroup Population)		Baseline, Week 24