Clinical trial 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia, Schizoaffective Disorder
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-08-13
Enrollment: 287
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4
timeFrame: Week 4 (Day 28)
Secondary outcomes:
measure: Change From Baseline in PANSS Factor Scores at Week 4
timeFrame: Week 4 (Day 28)
measure: Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score
timeFrame: Baseline to Week 12
measure: Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores
timeFrame: Week 4 (Day 28)
measure: Clinical Global Impression - Improvement (CGI-I) Scores
timeFrame: Week 4 (Day 28)
measure: PANSS Total Score at Week 12
timeFrame: Week 12
measure: Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12
timeFrame: Weeks 4, 8, and 12
measure: CGI-S up to Week 12
timeFrame: Up to Week 12
measure: CGI-I up to Week 12
timeFrame: Up to Week 12
measure: Participants Ready for Discharge From First Randomized Treatment Intake to Readiness for Discharge as Assessed by the Readiness for Discharge Questionnaire (RDQ) at 4-Week Treatment
timeFrame: after 4-week treatment
measure: Plasma Concentration of RO6889450
timeFrame: Day 7 - Day 336
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Woodland International Research Group Inc.
state: Arkansas
city: Bellflower
country: United States
facility: CITrials, Inc.
state: California
city: Culver City
country: United States
facility: ProScience Research Group
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, Inc.
state: California
city: Glendale
country: United States
facility: California Clinical Trials Medical Group managed by Parexel
state: California
city: Lemon Grove
country: United States
facility: Synergy San Diego
state: California
city: Orange
country: United States
facility: NRC Research Institute
state: California
city: Panorama City
country: United States
facility: ASCLEPES Research Centers
state: California
city: Pico Rivera
country: United States
facility: CNRI - Los Angeles, LLC
state: California
city: Riverside
country: United States
facility: CITrials, Inc.
state: California
city: San Diego
country: United States
facility: California Neuropsychopharmacology Clinical Research Institute, LLC
state: California
city: San Diego
country: United States
facility: Artemis Institute For Clinical Research LLC - San Diego - ClinEdge - PPDS
state: California
city: Sherman Oaks
country: United States
facility: Schuster Medical Research Institute
state: California
city: Hialeah
country: United States
facility: Galiz Research, LLC
state: Florida
city: Lauderhill
country: United States
facility: Innovative Clinical Research, Inc.
state: Florida
city: Miami
country: United States
facility: Premier Clinical Research Institute - Miami - BTC - PPDS
state: Florida
city: Oakland Park
country: United States
facility: Research Centers of America - ERG
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center For Medical Research
state: Georgia
city: Chicago
country: United States
facility: Uptown Research Institute
state: Illinois
city: Gaithersburg
country: United States
facility: CBH Health LLC
state: Maryland
city: Canton
country: United States
facility: Neuro-Behavioral Clinical Research, Inc.
state: Ohio
city: Dayton
country: United States
facility: Midwest Clinical Research Center - ERG - PPDS
state: Ohio
city: Austin
country: United States
facility: Community Clinical Research Inc.
state: Texas
city: Garland
country: United States
facility: Pillar Clinical Research LLC
state: Texas
city: Tokyo
country: Japan
facility: National Center of Neurology and Psychiatry
city: Toyoake
country: Japan
facility: Seishinkai Okehazama Hospital Fujita Kokoro Care Center
city: St-Petersburg
country: Russian Federation
facility: Leningradskiy Regional Psychoneurologic Dispensary
state: Sankt Petersburg
city: St. Petersburg
country: Russian Federation
facility: Psychiatry Hospital #1 n.a. P.P.Kashchenko
state: Sankt Petersburg
city: St. Petersburg
country: Russian Federation
facility: Psychiatric Hospital St Nicholas the Wonderworker
state: Sankt Petersburg
city: St. Petersburg
country: Russian Federation
facility: City Psychiatry Hospital #3 n.a. I.I. Skvortsov-Stepanov
state: Sankt Petersburg
city: Sankt-peterburg
country: Russian Federation
facility: FSBI National Medical Research Centre of Psychiatry and Neurology n.a. V.M. Bekhterev of MoH of RF
state: Vladimir
city: Saratov
country: Russian Federation
facility: Saratov regional clinical psychoneurological hospital St Sofii
city: Stavropol
country: Russian Federation
facility: Stavropol Regional Psychiatry Hospital #2
city: Tomsk
country: Russian Federation
facility: Tomsk National Scientific Medical Center of Russian Academy of Sciences
city: Kharkiv
country: Ukraine
facility: Communal Non-Commercial Enterprise of Kharkiv RC Regional clinical psychiatric hospital #3
state: Kharkiv Governorate
city: Kherson
country: Ukraine
facility: Public NPE Kherson Regional Institution of Mental Care of Kherson RC
state: Kherson Governorate
city: Kylv
country: Ukraine
facility: Kyiv Medical Regional Union Psychiatry
state: KIEV Governorate
city: Smila
country: Ukraine
facility: Communal Non-Commercial Enterprise Cherkasy Regional Psychiatric Hospital of Cherkasy RC
state: KIEV Governorate
city: Vinnytsia
country: Ukraine
facility: Communal NPE Vinnytsia Reg. Clin. Psychoneurolog. Hosp. n.a. O.I. Yushchenko of Vinnytsia RC
state: Podolia Governorate
city: Poltava
country: Ukraine
facility: Poltava Regional Psychiatry Hospital
state: Poltava Governorate
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: