E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with schizophrenia who are experiencing an acute exacerbation of psychosis |
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E.1.1.1 | Medical condition in easily understood language |
Schizophrenia is mental disorder that exhibits problems with positive symptoms (e.g. hallucinations), negative symptoms (e.g. lack of motivation) and cognitive deficits (e.g. information processing). |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10039628 |
E.1.2 | Term | Schizophrenia and other psychotic disorders |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039626 |
E.1.2 | Term | Schizophrenia |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of 2 fixed oral doses (15 mg QD and 30 mg QD) of emraclidine in adult participants with schizophrenia experiencing an acute exacerbation of psychosis |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of 2 fixed oral doses (15 mg QD and 30 mg QD) of emraclidine in adult participants with schizophrenia experiencing an acute exacerbation of psychosis |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female participants, ages 18 to 65 years, inclusive, at the time of signing the ICF 2. Primary diagnosis of schizophrenia per DSM-5, as confirmed by the MINI for Psychotic Disorders version 7.0.2 3. CGI-S ≥4 (moderately to severely ill) at the time of signing the ICF and Baseline 4. PANSS Total Score between 85 and 120, inclusive, at the time of signing the ICF and at Baseline. Additionally, participants must meet a score of ≥4 (moderate or greater) for ≥2 of the following Positive Scale items at the time of signing the ICF and at Baseline: • Positive Scale Item 1 (delusions) • Positive Scale Item 2 (conceptual disorganization) • Positive Scale Item 3 (hallucinatory behavior) • Positive Scale Item 6 (suspiciousness/persecution) 5. Experiencing an acute exacerbation or relapse of psychotic symptoms, with onset less than 60 days prior to signing the ICF. • Participant requires hospitalization for this acute exacerbation or relapse of symptoms • If participant is already an inpatient at the time of signing the ICF, has been hospitalized for ≤14 days for the current episode of psychosis at the time of signing the ICF, excluding hospitalization for psychosocial reasons 6. Scores as follows (normal to mild symptoms) at the time of signing the ICF and Baseline (Day 1): • All individual items of the SAS <2 • All individual items (Items 1-7) of the AIMS <2 • Clinical global assessment item of the BARS <3 7.Willing to discontinue all prohibited medications to meet protocol-required washouts prior to and during the trial period. 8.Resides in a stable living environment as demonstrated by the ability to provide contact information for themselves and/or family/friend/caregiver. |
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E.4 | Principal exclusion criteria |
1.Current DSM-5 diagnosis other than schizophrenia including, but not limited to, intellectual disability; schizoaffective disorder; major depressive disorder; schizophreniform disorder; psychotic depression; bipolar disorder; post-traumatic stress disorder; generalized anxiety disorder, obsessive compulsive disorder, eating disorders (bulimia, anorexia), or other anxiety disorders as a primary diagnosis (note: anxiety symptoms secondary to schizophrenia are allowed); delirium, dementia, amnestic, or other cognitive disorders. Acute depressive symptoms within 30 days prior to signing the ICF that require treatment with an antidepressant are exclusory. Acute manic symptoms within 30 days prior to signing the ICF that require treatment with a mood stabilizer are exclusory. Additional excluded conditions include borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder. 2.Any of the following: • Schizophrenia considered resistant/refractory to antipsychotic treatment by history (failure to respond to 2 or more courses of adequate pharmacological treatment defined as an adequate dose per label and a treatment duration of at least 4 weeks) • History of response to clozapine treatment only or failure to respond to clozapine treatment for schizophrenia 3.Any of the following regarding history of schizophrenia: • Time from initial onset of schizophrenia <2 years based on prior records or participant self-report • Presenting with an initial diagnosis of schizophrenia • Presenting for the first time with an acute psychotic episode requiring treatment 4.Reduction (improvement) in PANSS total score of ≥20% between Screening and Baseline. 5.Either of the following: • History of tardive dyskinesia • Extrapyramidal symptoms that required medication within 6 months prior to signing the ICF |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from Baseline at Week 6 in the PANSS total score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Change from Baseline at Week 6 in the CGI-S score |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
Bulgaria |
Hungary |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is defined as the date of the last visit (including follow-up safety contact) of the last participant in the trial globally |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |