E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
schizophrenia with persistent prominent negative symptoms |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 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 |
A study to evaluate the efficacy of 2 fixed-flexible doses of Lu AF11167 on negative symptoms in patients with schizophrenia |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• The patient has schizophrenia, diagnosed according to DSM-5® as confirmed by the Mini-International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorders Studies (MINI-Schz). • The patient has been known to the site and treated by the site for at least the last 12 months prior to Screening Visit 1. • The patient has suffered from persistent prominent negative symptoms for the last 6 months prior to the Screening Visit 1, in the opinion of the investigator and recorded in medical records. • The patient has been treated for schizophrenia with stable doses of an oral antipsychotic within the approved dose range and without any dose increase during the last 6 months prior to Screening Visit 1 (dose reductions are acceptable). • The patient has had no psychiatric admissions/hospitalization due to a clinical deterioration during the last 6 months prior to Screening Visit 1, this excludes ambulatory visits to ask for advice from the psychiatry team. • The patient is in a clinically stable phase of schizophrenia and has not more than moderate severity on relevant positive symptoms, that is a score of ≤4 (moderate) out of score of 7 on each of the following PANSS items: Delusions (P1), Hallucinatory behaviour (P3), Suspiciousness / persecution (P6), Uncooperativeness (G8), Unusual thought content (G9) at Screening Visit 1, Washout Visit(s), Screening Visit 2, and Baseline Visit and a score ≤5 on Conceptual disorganization (P2). • The patient currently has no clinically significant acute extrapyramidal side effects (acute EPS) or tardive dyskinesia (TD) based upon the protocol specified clinical examination. • The patient has prominent negative symptoms as demonstrated by a PANSS Marder Negative Symptom Factor Score (NSFS) ≥20 at Screening Visit 1, Washout Visit(s), Screening Visit 2, and Baseline Visit. NSFS is the sum of scores of the following PANSS items: Blunted affect (N1),Emotional withdrawal (N2), Poor rapport (N3), Passive/apathetic social withdrawal (N4), Lack of spontaneity & flow of conversation (N6), Motor retardation (G7) and Active social avoidance (G16). • The patient has a Clinical Global Impression-Schizophrenia Severity of Illness (CGI-SCH-S) overall severity score ≤4 at Screening Visit 1 and at the Baseline Visit. • The patient does not currently have a diagnosis of Major Depressive Disorder or have depressive symptoms rated with a total score ≥5 on the Calgary Depression Scale for Schizophrenia (CDSS). • The patient has no history of suicidal behaviour or violence for the last 12 months prior to Screening Visit 1. • The patient has a caregiver or an identified responsible person (for example, partner, family member, social worker, case worker, or nurse) considered reliable by the investigator in providing support to the patient to ensure compliance with study treatment, outpatient visits, and protocol procedures. |
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E.4 | Principal exclusion criteria |
• The patient has had an acute exacerbation requiring hospitalization within the last 6 months prior to Screening Visit 1. • The patient has had an acute exacerbation requiring change in antipsychotic medication (with reference to drug or dose) within the last 6 months prior to Screening Visit 1. • The patient has a current diagnosis or a history of substance use disorder according to DSM-5® criteria within 6 months prior to Screening Visit 1 with the exception of tobacco, or mild cannabis or mild alcohol use disorder (occasional – but not weekly recreational cannabis use is acceptable). Patients with a positive drug screen test for opiates, methadone, cocaine, amphetamines [including ecstasy], barbiturates, verified by repeated testing, are excluded from the study. • The patient is at significant risk of harming himself/herself or others in the investigator’s opinion. • The patient has tested positive for hepatitis A virus antibody (anti-HAV IgM), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (anti-HCV). If the anti-HCV test result is positive, but acute/chronic infection is excluded with a negative HCV RNA test patient can be included in the study. • The patient has tested positive for human immunodeficiency virus (HIV). • The patient has a present condition that might compromise liver function (for example, alcohol abuse, hepatitis, hepatic insufficiency, cholestasis, haemachromatosis, deficit in alpha 1 antitrypsine, Wilson’s Disease, autoimmune diseases, cirrhosis). • The patient has any other disorder for which the treatment takes priority over treatment of schizophrenia or is likely to interfere with the study treatment or impair treatment compliance. Other in- and exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change in Negative Symptom Scale (BNSS) total score
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
[1.Time Frame: from baseline to Week 12] |
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E.5.2 | Secondary end point(s) |
2. Change in Personal and Social Performance (PSP) score 3. Change in Positive and Negative Syndrome Scale (PANSS) total score 4. Change in PANSS Marder Negative Symptom Factor score: negative symptoms 5. Change in PANSS Negative subscale score 6. Change in Clinical Global Impression - Schizophrenia (CGI-SCH-S) negative symptoms score 7. Clinical Global Impression - Schizophrenia (CGI-SCH-DC) negative symptoms score 8.CGI-SCH-DC negative symptoms response 9.BNSS response 10.Change in PANSS -Positive subscale score 11.Change in Clinical Global Impression - Schizophrenia (CGI-SCH-S) severity of illness overall severity score 12.Clinical Global Impression - Schizophrenia (CGI-SCH-DC) degree of change in overall severity score 13.Change in Calgary Depression Scale for Schizophrenia (CDSS) total score
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
2.[Time Frame: from baseline to Week 12] 3.[Time Frame: from baseline to Week 12] 4.[Time Frame: from baseline to Week 12], 5.[Time Frame: from baseline to Week 12] 6.[Time Frame: from baseline to Week 12] 7.[Time Frame: at Week 12] 8.[Time Frame: at Week 12] 9.[Time Frame: at Week 12] 10.[Time Frame: from baseline to Week 12] 11.[Time Frame: from baseline to Week 12] 12.[Time Frame: at Week 12] 13.[Time Frame: from baseline to Week 12]
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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 | 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) | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
Bulgaria |
Estonia |
Germany |
Hungary |
Latvia |
Russian Federation |
Ukraine |
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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 overall end of the study is defined as the last protocol-specified contact with the last patient ongoing in the study. |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | 21 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 21 |