Schizophrenia
Conditions
Brief 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.
Interventions
DRUGPlacebo
Placebo will be administered orally QD for 56 weeks
DRUGRO4917838
RO4917838 will be administered orally at 20 or 10 mg QD for 56 weeks.
DRUGAntipshychotics (Standard of Care)
Participants will continue to receive their stable antipshychotic as standard of care based on their prescription up to Week 56.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| Percentage of Participants With Improvement From Baseline in the Overall Clinical Status Based on CGI-I Score (CFHR1 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 |
Countries
Argentina, Australia, Colombia, Finland, France, Hungary, India, Mexico, Romania, Russia, South Korea, Sweden, United Kingdom, United States
Outcome results
None listed