E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
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 |
The primary objective of this phase III pivotal trial in CIAS is to assess the efficacy in improving cognitive impairment using MCCB in patients with schizophrenia treated for 26 weeks with Iclepertin 10mg as compared with placebo. |
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E.2.2 | Secondary objectives of the trial |
The key secondary objective is to assess the efficacy in daily functioning of 26-week treatment with Iclepertin 10mg as compared with placebo in terms of Schizophrenia Cognition Rating Scale (SCoRS) and Virtual Reality Functional Capacity Assessment Tool (VRFCAT).
The secondary objectives are to assess the efficacy in improving reasoning and problem solving and patients’ experience of cognitive impairment associated with their disease. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated written informed consent in accordance with International Council on Harmonisation for Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial. 2. Male or female patients who are 18-50 years (inclusive) of age at time of consent. 3. Diagnosis of schizophrenia utilizing DSM-5 with the following clinical features: -- Outpatient, clinically stable and in the residual (non-acute) phase of their illness. -- No hospitalization or increase in level of psychiatric care due to worsening of schizophrenia within 12 weeks prior to randomization. -- PANSS score: items P1, P3-P6 ≤ 5 and item P2 and P7 ≤ 4 at Visit 1, and confirmed at Visit 2. 4. Patients should have functional impairment in day-to-day activities such as difficulties following conversation or expressing themselves, difficulties staying focused, difficulties remembering instructions, what to say or how to get to places, per investigator judgement. 5. Patients maintained on current antipsychotic treatment (minimum 1 and maximum 2 antipsychotics, but clozapine is not allowed) for at least 12 weeks and on current dose for at least 35 days prior to randomization. -- For patients on two antipsychotics, at least one antipsychotic must be within the approved label dose range. The second antipsychotic must not exceed the maximum daily dose per local label. 6. Patients with any other concomitant psychoactive medications (except for anticholinergics) need to be maintained on same drug for at least 12 weeks and on current dose/ regimen for at least 35 days prior to randomization. Maximum daily benzodiazepine load of up to 1 mg lorazepam-equivalent and hypnotic load up to 0.25 mg brotizolam-equivalent as needed (pro re nata, prn). Table of relevant medications and their equivalencies will be provided as a part of ISF -- For any other psychoactive medications cannot exceed the maximum daily dose per local label of the country where the study is being conducted.
Further criteria apply. |
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E.4 | Principal exclusion criteria |
1. Participant with current DSM-5 diagnosis other than Schizophrenia, including but not limited to bipolar, schizoaffective, major depressive disorder etc. M.I.N.I. for Psychotic disorders should be used for guidance. 2. Cognitive impairment due to developmental, neurological (e.g., epilepsy, stroke) or other disorders including head trauma, or patients with dementia or epilepsy. 3. Severe movement disorders -- Leading to cognitive impairment (e.g. Parkinson dementia), or -- Interfering with the efficacy assessments, or -- Due to antipsychotic treatment that cannot be controlled with low dose anticholinergic treatment (equal to maximum 1 mg benztropine twice daily). Table of relevant medications and their equivalencies will be provided as a part of ISF 4. Any suicidal behavior in the past 1-year prior to screening and during the screening period. 5. Suicidal ideation of type 5 in the C-SSRS (ie. active suicidal thought with plan and intent) in the past 3 months prior to screening and up to and including Visit 2. -- Patients with Suicidal Ideation type 4 in the C-SSRS (i.e. active suicidal thought with intent but without specific plan), within 3 months prior to screening and up to and including visit 2, can be randomized in the study, if assessed and documented by a licensed mental health professional that there is no immediate risk of suicide. 6. History of moderate or severe substance use disorder (other than caffeine and nicotine), as defined in DSM-5 within the last 12 months prior to informed consent. 7. Positive urine drug screen at Visit 1 based on central lab test. 8. Patients who were treated with any of the following within 6 months prior to randomization: -- Clozapine -- Stimulants (e.g. methylphenidate, dextroamphetamine, modafinil) -- Ketamine or esketamine -- Electroconvulsive therapy (ECT) or modified ECT
Further criteria apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Change from baseline in overall composite T-score of the MCCB after 26 weeks of treatment. |
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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) |
1) Change from baseline in the SCoRS interviewer total score after 26 weeks of treatment 2) Change from baseline to Week 26 in the adjusted total time T-score in the VRFCAT 3) Change from baseline to Week 26 in the T-score of the number of correct responses on ToL. 4) Change from screening visit 1a to Week 24 in Patient Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS) total score |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) week 26 2) week 26 3) week 26 4) week 24
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 |
Argentina |
Chile |
Malaysia |
Singapore |
Ukraine |
Brazil |
Japan |
Korea, Republic of |
Serbia |
United States |
Croatia |
France |
Hungary |
Netherlands |
Poland |
Romania |
Slovakia |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 24 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 24 |