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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03669640

Collaborator

(none)

247

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia, Schizoaffective Disorder	Drug: RO6889450 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

247 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 4, 2018

Anticipated Primary Completion Date :

May 6, 2023

Anticipated Study Completion Date :

May 6, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: Monotherapy Participants will receive RO6889450 or a dose-matched placebo. NOTE: Part A has completed enrollment.	Drug: RO6889450 Participants will receive a once-daily, oral dose of RO6889450 for 12 weeks. Drug: Placebo Participants will receive a once-daily, oral dose of placebo matched to RO6889450 for 12 weeks.
Experimental: Part B: Add-On Therapy 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 Participants will receive a once-daily, oral dose of RO6889450 for 12 weeks. Drug: Placebo Participants will receive a once-daily, oral dose of placebo matched to RO6889450 for 12 weeks.

Arm

Intervention/Treatment

Experimental: Part A: Monotherapy

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

Drug: RO6889450

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

Drug: Placebo

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

Experimental: Part B: Add-On Therapy

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

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

Drug: Placebo

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

Outcome Measures

Primary Outcome Measures

Change from Baseline at Week 12 in Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore [Baseline to Week 12]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CITrials, Inc.	Bellflower	California	United States	90706
2	CITrials - Santa Ana	Costa Mesa	California	United States	92626
3	Collaborative Neuroscience Network, Inc.	Garden Grove	California	United States	92845
4	California Clinical Trials	Glendale	California	United States	91206
5	Synergy San Diego	Lemon Grove	California	United States	91945
6	Catalina Research Institute LLC - MRA	Montclair	California	United States	91763
7	ASCLEPES Research Centers	Panorama City	California	United States	91402
8	CITrials, Inc.	Riverside	California	United States	92506
9	California Neuropsychopharmacology Clinical Research Institute, LLC	San Diego	California	United States	92102
10	Stanford University School of Medicine	Stanford	California	United States	94305
11	Collaborative Neuroscience Network Inc.	Torrance	California	United States	90502
12	Yale School of Medicine - CT Mental Health Center (CMHC) - Schizophrenia Research Clinic	New Haven	Connecticut	United States	06519
13	Innovative Clinical Research, Inc.	Lauderhill	Florida	United States	33319
14	Lifestream Behavioral Center	Leesburg	Florida	United States	34748
15	Premier Clinical Research Institute - Miami - BTC - PPDS	Miami	Florida	United States	33122
16	Advanced Research Institute of Miami	Miami	Florida	United States	33135
17	Health Synergy Clinical Research	Okeechobee	Florida	United States	34972
18	Jerome Golden Center for Behavioral Health	West Palm Beach	Florida	United States	33407
19	Emory University	Atlanta	Georgia	United States	30329
20	Northwestern University	Chicago	Illinois	United States	60611-2987
21	CBH Health	Gaithersburg	Maryland	United States	20877
22	University of Massachusetts Medical School; Child and Adolescent Psychiatry	Worcester	Massachusetts	United States	01605
23	Michigan Clinical Research Institute PC - Clinedge - PPDS	Ann Arbor	Michigan	United States	48105
24	Early Treatment and Cognitive Health (ETCH)	East Lansing	Michigan	United States	48823
25	Precise Research Centers	Flowood	Mississippi	United States	39232
26	Psych Care Consultants Research	Saint Louis	Missouri	United States	63128
27	Millennium Psychiatric Associates, LLC	Saint Louis	Missouri	United States	63132
28	Hassman Research Institute	Berlin	New Jersey	United States	08009
29	Princeton Medical Institiute	Princeton	New Jersey	United States	08540
30	New York State Psychiatric Institute	New York	New York	United States	10032
31	Manhattan Psychiatric Center; Psychopharmacology Research Unit	New York	New York	United States	10035
32	Carolina Clinical Trials Inc	Charleston	South Carolina	United States	29407
33	JPS Health Network	Fort Worth	Texas	United States	76104
34	Pillar Clinical Research LLC	Garland	Texas	United States	75042
35	Baylor College of Medicine	Houston	Texas	United States	77030
36	Baylor College of Medicine	Houston	Texas	United States	77030
37	University Hills Clinical Research	Irving	Texas	United States	75062
38	The Solace Center	Missouri City	Texas	United States	77459
39	Psychiatry & Behavioral Center	Richmond	Texas	United States	77406
40	Kohnodai Hp., National Center for Global Health and Medicine	Chiba		Japan	272-8516
41	National Hospital Organization Ryukyu Hospital	Kunigami		Japan	904-1201
42	Nankokokorono Clinic	Shirakawa		Japan	961-0021
43	National Center of Neurology and Psychiatry	Tokyo		Japan	187-8551
44	Seishinkai Okehazama Hospital Fujita Kokoro Care Center	Toyoake		Japan	470-1168
45	Hiyoshi Hospital	Yokohama-shi		Japan	223-0062
46	Hospital Universitario Central de Asturias	Oviedo	Asturias	Spain	33011
47	Corporacio Sanitaria Parc Tauli	Sabadell	Barcelona	Spain	08208
48	Hospital Universitario Marques de Valdecilla	Santander	Cantabria	Spain	39008
49	C.H. Regional Reina Sofia - PPDS	Cordoba		Spain	14004
50	Hospital Universitario 12 De Octubre	Madrid		Spain	28041
51	Hosp Univ Fundacion Alcorcon	Madrid		Spain	28922
52	Hospital Regional Universitario de Malaga - Hospital General	Malaga		Spain	29010
53	Complejo Asistencial Universitario de Salamanca - H. Clinico	Salamanca		Spain	37007
54	CNCE Regional Clinical Psychiatric Hospital of Kirovohrad Regional Council	Nove	Katerynoslav Governorate	Ukraine	25491
55	Communal Non-Commercial Enterprise of Kharkiv RC Regional clinical psychiatric hospital #3	Kharkiv	Kharkiv Governorate	Ukraine	61068
56	Public NPE Kherson Regional Institution of Mental Care of Kherson RC	Kherson	Kherson Governorate	Ukraine	73488
57	Municipal Non-Commercial Enterprise Odesa RMC for Mental Health of Odessa Regional Council	Odesa	Kherson Governorate	Ukraine	65006
58	ME Dnipropetrovsk Regional Clinical Hospital n.a. I.I Mechnykov Dnipropetrovsk Regional Council	Dnipro	KIEV Governorate	Ukraine	49005
59	Medical and diagnostic center Healthy and Happy of Limited Liability Company Healthy and Happy	Kyiv	KIEV Governorate	Ukraine	01033
60	Zakarpattia Regional Clinical Hospital n.a. Andrii Novak	Uzhhorod	KIEV Governorate	Ukraine	88000
61	Communal NPE Vinnytsia Reg. Clin. Psychoneurolog. Hosp. n.a. O.I. Yushchenko of Vinnytsia RC	Vinnytsia	Podolia Governorate	Ukraine	21037

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT03669640

Other Study ID Numbers:

BP40283

First Posted:

Sep 13, 2018

Last Update Posted:

Aug 22, 2022

Last Verified:

Aug 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Schizophrenia

Psychotic Disorders

Study Results

No Results Posted as of Aug 22, 2022