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History of Changes for Study: NCT04512066
A Trial of the Efficacy and the Safety of RO6889450 (Ralmitaront) vs Placebo in Patients With an Acute Exacerbation of Schizophrenia or Schizoaffective Disorder
Latest version (submitted September 15, 2023) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 August 12, 2020 None (earliest Version on record)
2 September 8, 2020 Recruitment Status, Study Status, Contacts/Locations and IPDSharing
3 October 13, 2020 Study Status, Study Identification, Contacts/Locations, Eligibility and Outcome Measures
4 November 9, 2020 Study Status
5 December 8, 2020 Study Status and Contacts/Locations
6 January 7, 2021 Contacts/Locations and Study Status
7 February 2, 2021 Contacts/Locations and Study Status
8 March 1, 2021 Study Status and Contacts/Locations
9 March 29, 2021 Contacts/Locations and Study Status
10 April 26, 2021 Study Status and Contacts/Locations
11 May 25, 2021 Study Status
12 June 21, 2021 Study Status and Outcome Measures
13 July 21, 2021 Study Status
14 August 18, 2021 Study Status and Contacts/Locations
15 August 25, 2021 Arms and Interventions, Eligibility and Study Status
16 September 22, 2021 Study Status
17 October 21, 2021 Study Status, Contacts/Locations, Eligibility and Outcome Measures
18 November 16, 2021 Contacts/Locations and Study Status
19 December 14, 2021 Contacts/Locations and Study Status
20 January 10, 2022 Contacts/Locations and Study Status
21 February 9, 2022 Study Status
22 March 10, 2022 Study Status and Contacts/Locations
23 April 7, 2022 Contacts/Locations and Study Status
24 May 5, 2022 Study Status and Contacts/Locations
25 June 3, 2022 Study Status and Contacts/Locations
26 June 16, 2022 Recruitment Status, Study Status, Contacts/Locations and Study Design
27 July 14, 2022 Study Status and Contacts/Locations
28 April 21, 2023 Study Status
29 June 16, 2023
Quality Control Review has not concluded Returned: July 11, 2023
Recruitment Status, Outcome Measures, Study Status, Document Section, Contacts/Locations and Study Design
30 July 28, 2023
Quality Control Review has not concluded Returned: August 21, 2023
Outcome Measures, Study Status
31 September 15, 2023 Outcome Measures, Study Status
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Changes (Merged) for Study: NCT04512066
June 3, 2022 (v25) -- June 16, 2022 (v26)

Changes in: Study Status, Study Design and Contacts/Locations

Open or close this module Study Identification
Unique Protocol ID: BP41743
Brief Title: A Trial of the Efficacy and the Safety of RO6889450 (Ralmitaront) vs Placebo in Patients With an Acute Exacerbation of Schizophrenia or Schizoaffective Disorder
Official Title: A Phase II, Multi-Center, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Trial of the Efficacy and the Safety of RO6889450 (Ralmitaront) vs Placebo in Patients With an Acute Exacerbation of Schizophrenia or Schizoaffective Disorder
Secondary IDs:
Open or close this module Study Status
Record Verification: June 2022
Overall Status: Recruiting Terminated [In a preliminary analysis, the primary endpoint was negative, and ongoing portions of the study have therefore been discontinued.]
Study Start: September 8, 2020
Primary Completion: July 31, 2022 [Anticipated] May 13, 2022 [Actual]
Study Completion: April 23, 2023 [Anticipated] May 13, 2022 [Actual]
First Submitted: August 12, 2020
First Submitted that
Met QC Criteria:
August 12, 2020
First Posted: August 13, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
June 3 16, 2022
Last Update Posted: June 6 22, 2022 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Hoffmann-La Roche
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring:
Open or close this module Study Description
Brief Summary: This study will investigate the efficacy and safety of RO6889450 as monotherapy in participants experiencing an acute exacerbation of symptoms of schizophrenia or schizoaffective disorder.
Detailed Description:
Open or close this module Conditions
Conditions: Schizophrenia, Schizoaffective Disorder
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 4
Masking: Double (Participant, Investigator)
Allocation: Randomized
Enrollment: 308 [Anticipated] 286 [Actual]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: 150 mg Once Daily (QD) RO6889450
Participants will receive 150 mg of RO6889450 QD for 4 weeks or 12 weeks or 48 weeks.
Drug: RO6889450
Participants will receive oral RO6889450 QD.
Experimental: 45 mg QD RO6889450
Participants will receive 45 mg of RO6889450 QD for 4 weeks or 12 weeks or 48 weeks.
Drug: RO6889450
Participants will receive oral RO6889450 QD.
Placebo Comparator: Placebo
Participants will receive oral placebo QD for 4 weeks. Participants from this arm that continue to the extension period will be randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks or additional 44 weeks (optional 36-Week Safety Extension Phase).
Drug: Placebo
Participants will receive oral placebo QD.
Active Comparator: 4 mg QD Risperidone
Participants will receive 4 mg of risperidone QD for 4 weeks or 12 weeks or 48 weeks.
Drug: Risperidone
Participants will receive oral risperidone QD.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Change from Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score
[ Time Frame: Baseline to Week 4 ]

Secondary Outcome Measures:
1. Proportion of Participants with at least 20% or 50% Improvement from Baseline in the PANSS Total Score
[ Time Frame: Baseline to Week 12 ]

2. Change from Baseline in the PANSS Total and Factor Scores
[ Time Frame: Baseline to Week 12 ]

3. Proportion of Participants with at Least 20% or 50% Improvement in the PANSS Factor Scores
[ Time Frame: Baseline to Week 12 ]

4. Change from Baseline in Clinical Global Impression Severity (CGI-S) Scores
[ Time Frame: Baseline to Week 12 ]

5. Clinical Global Impression - Improvement (CGI-I) Scores
[ Time Frame: Baseline to Week 12 ]

6. Clinical Global Impression - Improvement Most Troubling Symptoms (CGI-I MTS)
[ Time Frame: Baseline to Week 12 ]

7. Change from Baseline in Clinical Global Impression - Severity Most Troubling Symptoms (CGI-S MTS)
[ Time Frame: Baseline to Week 12 ]

8. Time from First Randomized Treatment Intake to Readiness for Discharge as Assessed by the Readiness for Discharge Questionnaire (RDQ)
[ Time Frame: Baseline to Week 4 ]

9. Percentage of Participants with Adverse Events (AEs)
[ Time Frame: Baseline to Week 12 ]

10. Change from Screening in Electrocardiogram (ECG) Intervals
[ Time Frame: Baseline to Week 12 ]

11. Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)
[ Time Frame: Baseline to Week 12 ]

12. Change from Baseline in Extrapyramidal Symptom Rating Scale (ESRS-A)
[ Time Frame: Baseline to Week 12 ]

13. Maximum Concentration (Cmax) of RO6889450
[ Time Frame: Baseline to Week 12 ]

14. Area Under the Concentration-Time Curve at Steady State (AUCss) of RO6889450
[ Time Frame: Baseline to Week 4 ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 45 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion criteria

  • Participant must be 18 to 45 years of age inclusive
  • Participants with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of schizophrenia or schizoaffective disorder as confirmed by the Mini International Neuropsychiatric Interview (MINI)
  • Disease duration </=10 years
  • Have a current acute exacerbation of schizophrenia of no more than 8 weeks before screening visit and no current signs of apparent lack of treatment response
  • At the time of screening, the participant needs to be either hospitalized or requiring inpatient psychiatric care according to clinical judgment. If the participant has been hospitalized for the current exacerbation, the hospitalization has to be of a maximum of 1 week prior to screening.
  • In previous exacerbations and hospitalizations, the subject has shown a pattern of response to appropriate antipsychotic treatment
  • Medically stable over a period of 3 months (non-psychiatric conditions) prior to screening visit and not expected to require hospitalization or change of treatment for non-psychiatric conditions for the duration of the study
  • Screening and baseline CGI-S >/=4 (moderate or worse)
  • Screening and baseline PANSS total score >= 80
  • Based on screening and baseline PANSS, scores of >/= 4 (moderate or worse) on 2 or more of the following items: delusions, conceptual disorganization, unusual thought content, hallucinatory behavior, or suspiciousness/persecution
  • Body mass index between 18 and 35 kg/m2 inclusive
  • Male and female participants; female participants 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

Additional inclusion criteria for optional 36-Week Safety Extension Phase

  • Successful completion of the 12-week treatment period
  • No signs or symptoms of worsening of the psychiatric or medical status that would preclude the patient from the participation in the 36-Week Safety Extension Phase or affect their ability to comply with the study requirements.

Exclusion criteria

  • Has been inpatient for > 1 week or had any other hospitalization for acute exacerbation of schizophrenia or schizoaffective disorder within the prior 8 weeks or signs of lack of response to antipsychotic treatment
  • Disease duration > 10 years
  • Is currently an inpatient on an involuntary basis
  • Subject answers "yes" to "Suicidal Ideation" Item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) or any suicidal behavior on the Columbia-Suicide Severity Rating Scale (C-SSRS) assessment within one month from screening or between screening and baseline
  • Lifetime history of homicidal behavior
  • Moderate to severe substance use disorder within six months (excluding nicotine) as defined by DSM-5
  • Other current DSM-5 diagnosis (e.g., bipolar disorder, major depressive disorder)
  • A prior or current general medical condition that might be impairing cognition or other psychiatric functioning (e.g., migraine headaches requiring prophylaxis treatment, head trauma, dementia, seizure disorder, stroke; or neurodegenerative, inflammatory, infectious, neoplastic, toxic, metabolic, or endocrine conditions)
  • Clinically significant abnormalities in laboratory safety test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis), including a) Aspartate aminotransferase (AST), OR alanine aminotransferase (ALT) 2 x upper limit of normal (ULN), OR total bilirubin > 1.5 ULN with the exception of known Gilbert syndrome. b) Serum creatinine > 1.5 ULN
  • Positive result at screening for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV, untreated), or human immunodeficiency virus (HIV)-1 and -2. HCV participants who have been successfully treated and who test negative for HCV RNA are eligible for entry into the study
  • Tardive dyskinesia that is moderate to severe or requires treatment
  • History of neuroleptic malignant syndrome
  • Average triplicate QTcF interval greater than 450 msec for males and 470 msec for females or other clinically significant abnormality on screening ECG based on centralized reading
  • Participant for whom risperidone is contraindicated or who have a documented history of lack of response or intolerance to risperidone or paliperidone or participants with known hypersensitivity to risperidone, paliperidone, or to any excipients in Risperdal
  • Participant treated with a long acting injectable antipsychotic or other antipsychotics that cannot be washed-out within the allotted screening period
  • History of electro-convulsive therapy (ECT) for any reason
  • Participant treated with clozapine at any dose within 12 months of screening visit or participants treated with clozapine at 200 mg/day or above at any time; low dose (< 200mg/day) use for insomnia or dyskinesia longer than 12 months prior to screening visit is permitted
  • Participants currently receiving a psychotropic or other medication used as a psychotropic, which cannot be discontinued during the screening period
  • Positive urine drug screen for amphetamines, methamphetamines, opiates, buprenorphine, methadone, cocaine and barbiturates. In case of positive urine drug screen for cannabinoids, the participant may be allowed to enter the study if approved by Medical Monitor
  • Participant has previously received RO6889450
  • Participant received an investigational drug within 28 days or five times the half-life of the investigational drug prior to the first study drug administration
  • 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
Open or close this module Contacts/Locations
Central Contact Person: Reference Study ID Number: BP41743 https://forpatients.roche.com/
Telephone: 888-662-6728
Email: global-roche-genentech-trials@gene.com
Study Officials: Clinical Trials
Study Director
Hoffmann-La Roche
Locations: United States, Arkansas
Woodland International Research Group Inc.
[Active, not recruiting]
Little Rock, Arkansas, United States, 72211
Woodland Research Northwest LLC - ERG - PPDS
[Active, not recruiting]
Rogers, Arkansas, United States, 72758
United States, California
CITrials, Inc.
[Completed]
Bellflower, California, United States, 90706
ProScience Research Group
[Completed]
Culver City, California, United States, 90230
Collaborative Neuroscience Network, Inc.
[Completed]
Garden Grove, California, United States, 92845
California Clinical Trials Medical Group managed by Parexel
[Completed]
Glendale, California, United States, 91206
Synergy San Diego
[Completed]
Lemon Grove, California, United States, 91945
North County Clinical Research
[Withdrawn]
Oceanside, California, United States, 92056
NRC Research Institute
[Completed]
Orange, California, United States, 92868
ASCLEPES Research Centers
[Completed]
Panorama City, California, United States, 91402
CNRI - Los Angeles, LLC
[Completed]
Pico Rivera, California, United States, 90660
CITrials, Inc.
[Active, not recruiting]
Riverside, California, United States, 92506
California Neuropsychopharmacology Clinical Research Institute, LLC
[Completed]
San Diego, California, United States, 92102
Artemis Institute For Clinical Research LLC - San Diego - ClinEdge - PPDS
[Completed]
San Diego, California, United States, 92103
Schuster Medical Research Institute
[Completed]
Sherman Oaks, California, United States, 91403
United States, Florida
Galiz Research, LLC
[Completed]
Hialeah, Florida, United States, 33016
Innovative Clinical Research, Inc.
[Completed]
Lauderhill, Florida, United States, 33319
Premier Clinical Research Institute - Miami - BTC - PPDS
[Completed]
Miami, Florida, United States, 33122
Research Centers of America - ERG
[Completed]
Oakland Park, Florida, United States, 33334
United States, Georgia
Atlanta Center For Medical Research
[Completed]
Atlanta, Georgia, United States, 30331
United States, Illinois
Uptown Research Institute
[Completed]
Chicago, Illinois, United States, 60640
United States, Louisiana
Louisiana Clinical Research, LLC
[Active, not recruiting]
Shreveport, Louisiana, United States, 71115
United States, Maryland
CBH Health LLC
[Completed]
Gaithersburg, Maryland, United States, 20877
United States, New Jersey
Hassman Research Institute - ClinEdge - PPDS
[Withdrawn]
Berlin, New Jersey, United States, 08009
United States, New York
New York State Psychiatric Institute
[Active, not recruiting]
New York, New York, United States, 10032
United States, Ohio
Neuro-Behavioral Clinical Research, Inc.
[Completed]
Canton, Ohio, United States, 44718
Midwest Clinical Research Center - ERG - PPDS
[Completed]
Dayton, Ohio, United States, 45415
United States, Texas
Community Clinical Research Inc.
[Completed]
Austin, Texas, United States, 78754
Pillar Clinical Research LLC
[Active, not recruiting]
Garland, Texas, United States, 75042
Pillar Clinical Research LLC
[Completed]
Garland, Texas, United States, 75042
Japan
Kohnodai Hp., National Center for Global Health and Medicine
[Recruiting]
Chiba, Japan, 272-8516
Kusatsu Hospital; Psychiatry
[Recruiting]
Hiroshima, Japan, 733-0864
Narimasu Kosei Hospital
[Recruiting]
Itabashi, Japan, 175-0091
Nishigahara Hospital
[Recruiting]
Kita-ku, Japan, 114-0024
National Hospital Organization Ryukyu Hospital
[Recruiting]
Kunigami, Japan, 904-1201
Shironishi Medical Foundation Shironishi Hospital
[Recruiting]
Matsumoto, Japan, 390-8648
National Hospital Organization Hizen Psychiatric Center; Psychiatry
[Recruiting]
Saga, Japan, 842-0192
National Center of Neurology and Psychiatry
[Recruiting]
Tokyo, Japan, 187-8551
Seishinkai Okehazama Hospital Fujita Kokoro Care Center
[Recruiting]
Toyoake, Japan, 470-1168
Russian Federation
Saratov regional clinical psychoneurological hospital St Sofii
[Active, not recruiting]
Saratov, Russian Federation, 410060
Stavropol Regional Psychiatry Hospital #2
[Active, not recruiting]
Stavropol, Russian Federation, 357034
Tomsk National Scientific Medical Center of Russian Academy of Sciences
[Active, not recruiting]
Tomsk, Russian Federation, 634009
Russian Federation, Moskovskaja Oblast
Mental Health Research Center of RAMN
[Withdrawn]
Moscow, Moskovskaja Oblast, Russian Federation, 115522
Russian Federation, Sankt Petersburg
Leningradskiy Regional Psychoneurologic Dispensary
[Active, not recruiting]
St-Petersburg, Sankt Petersburg, Russian Federation, 188820
Psychiatry Hospital #1 n.a. P.P.Kashchenko
[Active, not recruiting]
St. Petersburg, Sankt Petersburg, Russian Federation, 188357
Psychiatric Hospital St Nicholas the Wonderworker
[Active, not recruiting]
St. Petersburg, Sankt Petersburg, Russian Federation, 190121
City Psychiatry Hospital #3 n.a. I.I. Skvortsov-Stepanov
[Active, not recruiting]
St. Petersburg, Sankt Petersburg, Russian Federation, 197341
Russian Federation, Vladimir
FSBI National Medical Research Centre of Psychiatry and Neurology n.a. V.M. Bekhterev of MoH of RF
[Active, not recruiting]
Sankt-peterburg, Vladimir, Russian Federation, 192019
Ukraine, KIEV Governorate
Kyiv Medical Regional Union Psychiatry
[Completed]
Kylv, KIEV Governorate, Ukraine, 04080
Communal Non-Commercial Enterprise Cherkasy Regional Psychiatric Hospital of Cherkasy RC
[Active, not recruiting]
Smila, KIEV Governorate, Ukraine, 20708
Ukraine, Kharkiv Governorate
Communal Non-Commercial Enterprise of Kharkiv RC Regional clinical psychiatric hospital #3
[Active, not recruiting]
Kharkiv, Kharkiv Governorate, Ukraine, 61068
Ukraine, Kherson Governorate
Public NPE Kherson Regional Institution of Mental Care of Kherson RC
[Active, not recruiting]
Kherson, Kherson Governorate, Ukraine, 73488
Municipal Non-Commercial Enterprise Odesa RMC for Mental Health of Odessa Regional Council
[Active, not recruiting]
Odesa, Kherson Governorate, Ukraine, 65006
Ukraine, Podolia Governorate
Communal NPE Vinnytsia Reg. Clin. Psychoneurolog. Hosp. n.a. O.I. Yushchenko of Vinnytsia RC
[Withdrawn]
Vinnytsia, Podolia Governorate, Ukraine, 21037
Communal NPE Vinnytsia Reg. Clin. Psychoneurolog. Hosp. n.a. O.I. Yushchenko of Vinnytsia RC
[Completed]
Vinnytsia, Podolia Governorate, Ukraine, 21037
Ukraine, Poltava Governorate
Poltava Regional Psychiatry Hospital
[Completed]
Poltava, Poltava Governorate, Ukraine, 36030
Ukraine, Volhynian Governorate
Communal Nonprofit enterprise Ternopil Regional Clinical Psychoneurological Hospital of TRC
[Active, not recruiting]
Ternopil, Volhynian Governorate, Ukraine, 46027
Open or close this module IPDSharing
Plan to Share IPD: Yes
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Supporting Information:
Time Frame:
Access Criteria:
URL:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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