E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with diagnosis of AD according to the following criteria:
• Symptoms noticed by the patients and/or informant
• Cognitive testing confirming symptoms
• Biomarker evidence of AD pathology
• No evidence of other forms of dementia
• No other concomitant illness or medication which could confound or prohibit completion in the trial by the patient
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E.1.1.1 | Medical condition in easily understood language |
Patients who suffer by mental disorders which are caused by symptoms of the Alzheimer's Disease |
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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 | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
E.1.2 | System Organ Class | 100000004852 |
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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 assess efficacy of different doses of BI 409306 compared to placebo in treatment of Alzheimers' Disease (AD) |
Avaliar a eficácia, segurança e tolerabilidade de diferentes doses de BI 409306 em comparação com placebo no tratamento da Doença de Alzheimer prodrómica |
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E.2.2 | Secondary objectives of the trial |
To assess safety and tolerability of different doses of BI 409306 compared to placebo in treatment of Alzheimers' Disease (AD) |
Avaliar a eficácia, segurança e tolerabilidade de diferentes doses de BI 409306 em comparação com placebo no tratamento da Doença de Alzheimer prodrómica |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male and female patients with an age of at least 55 years
- Body weight not lower than 50 kgs
- Patients with early signs of Alzheimer Disease
- Within three months prior to screening patients who have not received prescribed drugs for treatment of AD (including acetyl cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, phenserine) and Memantine
- Patients must have at least 6 years of formal education and fluency in the test language as verbally confirmed by the patient and documented by the study investigator.
- All patients must be able to give informed consent personally and have capacity for such consent. An informed consent given by a legal representative will not be accepted.
- Patients must have a reliable study partner (per investigator judgement, for instance a family member, partner etc., guardian)
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E.4 | Principal exclusion criteria |
- Mild cognitive impairment with any etiology other than prodromal AD (for example: neurosyphilis, craniocerebral trauma, small vessel disease) based on clinical data and/or current laboratory findings and/or a pre-existing MRI or CT of the brain (CCT). If previous cranial imaging is not available or older than 12 months prior to sreening then a CCT or MRI needs to be performed and sreening.
- Substantial concomitant cerebrovascular disease (defined by a history of a stroke / intracranial haemorrhagia) temporally related to the onset of worsening of cognitive impairment per investigator judgement
- Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
- Medical history or diagnosis of any of symptomatic and unstable/uncontrolled conditions per investigator judgement
-Severe renal impairment defined with a glomerular filtration rate (GFR) < 30ml/min/1.73m2 in the screening the central lab report
-Any other psychiatric disorders such as schizophrenia, or mental retardation
-Any suicidal actions in the past 2 years (per investigator judgement i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour)
-Any suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale (C-SSRS) in the past 3 months (i.e. active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent)
-Previous participation in investigational drugs studies of mild cognitive impairment within three months prior to sreening. Having received active treatment in any other study targeting disease modification like AB immunization and tau therapies. Previous participation in studies with non-prescription medications, vitamins or other nutritional formulations is allowed.
-Significant history of drug dependence or abuse (including alcohol, as defined in Diagnostic ans Statistical Manual or Mental Disorders [DSM-V] or in the opinion of the investigator) within the last two years, or a positive urine drug scree for cocaine, heroin or marijuana.
-Known hystory of HIV infection
-Any planned surgeries requiring general anaesthesia, or hospitalisation for more than 1 day during the study period
-Pre-menopausal women (last menstruation = 1 year prior to informed consent) who are nursing or pregnant or are of child-bearing potential and are not practicing an acceptable method of birth control
- Form male patients: Men who are able to father a child, unwilling to be abstinent or to use two different forms of effective contraception fopr the duration of study participation and for at least 28 days after treatment has ended.
-Use of any investigational drug or procedure for other indications within 3 months or 6 half-lives (whichever is longer) prior to randomization.
-Intake of medications which might interfere with the study drug within 3 months prior to randomization and intended to be initiated during the duration of the trial
-Clinically significant uncompensated hearing loss in the judgment of the investigator. Use of hearing aids is allowed.
- Known hypersensitivity to the drug product excipients |
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E.5 End points |
E.5.1 | Primary end point(s) |
1: The primary endpoint is Neuropsychological Test Battery (NTB) response, defined as
change from baseline in total score after 12-week 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 ADCS-MCI-ADL (Alzheimer's Disease Cooperative Study/Activities of Daily Living scale adapted for MCI patients) total score after 12-week treatment.
2: Change from baseline CDR-SB (Clinical Dementia Rating, Sum of Boxes) after 12-week treatment
3: Change from baseline in ADAS-Cog11 (Alzheimers Disease Assessment Scale cognitive subscale) total score after 12-week treatment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: 12 weeks
2: 12 weeks
3: 12 weeks
4: 12 weeks |
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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 | 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) | 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 | 5 |
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 | 44 |
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 |
Austria |
Belgium |
Canada |
France |
Germany |
Italy |
Netherlands |
Poland |
Portugal |
Spain |
United Kingdom |
United States |
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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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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 | 9 |
E.8.9.1 | In the Member State concerned days | 26 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 11 |