A Study to Evaluate the Effects of RO6889450 (Ralmitaront) in Patients with Schizophrenia or Schizoaffective Disorder and Negative Symptoms

Phase 1

• Conditions: Schizophrenia or schizoaffective disorder; MedDRA version: 21.1Level: PTClassification code 10039621Term: Schizoaffective disorderSystem Organ Class: 10037175 - Psychiatric disorders; MedDRA version: 20.0Level: PTClassification code 10039626Term: SchizophreniaSystem Organ Class: 10037175 - Psychiatric disorders; Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

• Registration Number: EUCTR2020-004752-16-ES
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-02-09
• Last Update Posted: 10 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

• Male or female participants aged 18-55 years (inclusive)
• Patients 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)
• Part B only: Stable treatment with a dopamine 2 receptor (D2)/serotonin 2A receptor (5HT2A) antagonists or pure D2 antagonist(s), or a D2 partial agonist for a minimum of six months and receiving no more than two antipsychotics (if no blood concentration of the prescribed antipsychotic medication [or active metabolites] is detected, the participant should not be enrolled). Antipsychotic regimen: participants must be on a primary antipsychotic and may be on a secondary antipsychotic. The secondary antipsychotic dose must be equal to or less than the equivalent dose of the primary antipsychotic. The sum of the primary and secondary antipsychotics must be <=6 mg of risperidone equivalents
• Medically stable during the prior three months. Medication changes (other than antipsychotics) in the three months prior to screening may be acceptable after discussion with and approval by the Medical Monitor
• Participant is outpatient with no psychiatric hospitalizations within the prior six months (hospitalization for social management within this time is acceptable)
• PANSS-negative symptom factor score (PANSS-NSFS) score of 18 or higher
• Rating on items of the PANSS: less than 5 on G8 (uncooperativeness), P1 (delusions), P3 (hallucinations), P4 (excitement/hyperactivity), and P6 (suspiciousness/persecution); and less than 4 on P7 (hostility) and G14 (poor impulse control)
• Has an informant who is considered reliable by the Investigator to provide support to the participant and to help ensure compliance with study visits and protocol procedures; who preferably is also able to provide input helpful for completing study rating scales and is in regular contact with the participant in order to be able to alert the Investigator of worsening signs and symptoms for the participant
• Body mass index (BMI) between 18 and 35 kilograms per square metre (kg/m^2) inclusive
• A woman is eligible to participate if she is not pregnant (negative serum pregnancy test at screening and negative urine pregnancy test at baseline), not breastfeeding, not a woman of childbearing potential (WOCBP), or WOCBP who agrees 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 220
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• Part A only: Confirmed suicidal behavior based on Investigator judgment or violent behavior resulting in injury or property damage in the prior five years. A history prior to the last five years requires approval by the patient review committee (PRC) on a case-by-case basis
• Part A only: Lifetime history of homicidal behavior
• Moderate to severe substance use disorder within six months (excluding nicotine) as defined by DSM-5
• Extrapyramidal symptom rating scale (ESRS) total score greater 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 (e.g., migraine headaches requiring prophylactic treatment, head trauma, dementia, seizure disorder, stroke; or neurodegenerative, inflammatory, infectious, neoplastic, toxic, metabolic, endocrine conditions)
• Positive result at screening for hepatitis B surface antigen (HBsAg), hepatitis C (hepatitis C antibody), or human immunodeficiency virus (HIV)-1 and -2. hepatitis C (HCV) antibody positive patients are eligible if HCV ribonucleic acid (RNA) is negative
• Tardive dyskinesia that is moderate to severe or requires treatment
• History of neuroleptic malignant syndrome
• Average triplicate QTcF interval greater than 450 millisecond (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 (including hepatic and renal panels, complete blood count, chemistry panel, coagulation, and urinalysis)
o Aspartate transaminase (AST), alanine transaminase (ALT) >2 X upper limit of normal (ULN)
o Total bilirubin >1.5 ULN with the exception of Gilbert syndrome
o Serum creatinine >1.5 ULN
• Significant or unstable physical condition that in the Investigator’s judgment might require a change in medication or hospitalization during the study
• On more than one antidepressant (trazodone used at a dose up to and including 50 mg at bedtime is considered a hypnotic agent), or if on one antidepressant, a change in dose within 28 days prior to screening
• Any history of clozapine treatment
• History of treatment with electroconvulsive therapy (ECT)
• Concomitant use of prohibited medications
• Positive urine drug screen for amphetamines, methamphetamines, opiates, buprenorphine, methadone, cannabinoids, cocaine and barbiturates. In case of uncertain or questionable results, the urine drug screen may be repeated once during the screening period to confirm eligibility
• 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 milliliter (mL) within three months prior to screening
• Diagnosis of corona virus (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
• Part A only: Participant will be excluded if unable to taper off an antipsychotic in the one week prior to baseline (e.g., in the case of symptom exacerbation or ant

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified