| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Cognitive impairment due to Alzheimer's Disease
Patients with diagnosis of mild-to moderate Alzheimer’s dementia according to the recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease.
Protocol date: 12 JUL 2018
Protocol Version: 5.0 |
|
| E.1.1.1 | Medical condition in easily understood language |
| Cognitive impairment due to Alzheimer's Disease |
|
| 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 | 10012271 |
| E.1.2 | Term | Dementia Alzheimer's type |
| E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
| 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 | 10029205 - Nervous system disorders |
|
| 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 safety, tolerability and efficacy of different doses of BI 425809 compared to placebo in treatment of cognitive impairment due to Alzheimer¿s Disease |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Sub-study Title: A multi-centre, double-blind, parallel-group, randomized controlled study to investigate efficacy and safety of orally administered BI 425809 during a 12-week treatment period compared to placebo in patients with cognitive impairment due to Alzheimer’s Disease.
Rationale and Objectives: The sub-study will be implemented in Germany, in the US, France, Japan and in Poland and it may be implemented within further countries participating in 1346.23. The sub-study intends to investigate the ocular safety of different doses of BI 425809 in patients with Alzheimer’s Disease Dementia. |
|
| E.3 | Principal inclusion criteria |
- Patients with signs of dementia of Alzheimer Type
- Male and female patients with an age of at least 55 years
- MMSE 15-26
- All patients must sign and date an Informed Consent Form personally
- Concomitant use of AChEIs is allowed but not required. Patients who are currently taking AChEIs are eligible as long as they have been using a stable dose for at least 3 months prior to screening and no change is foreseen for the duration of the study. This dose must be consistent with the product label in the concerned country. Patients who are not currently taking AChEIs but have taken them in the past are also eligible if AChEIs were stopped at least 3 months prior to screening.
- 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.
- Patients must have a reliable study partner (per investigator judgement, for instance a family member, partner etc., guardian or, if applicable, a legal representative)
Ophthalmological Sub-study inclusion criteria:
1.Patients who have given informed consent to participate in the 1346.23 and who (at the end of the screening visit procedures) can be foreseen to be randomised to active treatment in the discretion of the investigator.
2.Patients must have given written informed consent to the sub-study in accordance with
GCP and local legislation prior to any sub-study related procedures
|
|
| E.4 | Principal exclusion criteria |
- Dementia secondary to disorders other than Alzheimer's Disease Dementia. Lewy body dementia or vascular or multi-infarct dementia as
primary diagnosis is excluded.
performed at screening.
- Any central nervous system disease other than AD which according to the investigator
may be associated with worsening of cognition. Patients with epileptic seizure in last 2
years should be excluded.
- A disease or condition which in the opinion of the investigator are likely to interfere
with trial testing procedures or put the patient at risk when participating in this trial.
- Any documented active or suspected malignancy or history of malignancy with need of
concomitant treatment that interfere with the investigational product.
- Patients with life expectancy of less than 2 years are also excluded.
- Any other clinical condition that, in the opinion of the investigator, would jeopardize
patient safety while participating in this clinical trial.
- Severe renal impairment defined as a GFR < 30 mL/min/1.73 m2 in the screening central lab report.
- Haemoglobin less than 120 g/L (12g/dL) in men or 115g/L (11.5g/dL) in women in the
screening lab report.
- Clinically significant uncompensated hearing loss in the judgment of the investigator.
Use of hearing aids is allowed.
- Any suicidal behaviour in the past 2 years (i.e. actual attempt, interrupted attempt,
aborted attempt, or preparatory acts or behaviour).
- Any suicidal ideation of type 4 or 5 in the 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).
- Known history of HIV infection.
- Significant history of drug dependence or abuse (including alcohol, as defined in
Diagnostic and Statistical Manual of Mental Disorders [DSM-V] or in the opinion of the
investigator) within the last two years.
- Previous participation in investigational drug studies of dementia of Alzheimer’s Type
within three months prior to screening. Patients having received any active treatment in
studies targeting disease modification of AD are excluded.
Previous participation in studies with non-prescription medications, vitamins other
nutritional formulations or non-pharmacological treatments is allowed.
- Treatment with restricted medication.
- Planned elective surgery requiring general anaesthesia, or hospitalisation for more than
1 day (requiring an overnight stay) during the study period.
- For females: Women who are of child bearing potential. Women not of childbearing
potential are defined as: Women who are postmenopausal (12 months with no menses
without an alternative medical cause) or who are permanently sterilized (e.g.
hysterectomy, bilateral oophorectomy or bilateral salpingectomy).
For males: Men who are able to father a child, unwilling to be abstinent or to use an
adequate form of effective contraception for the duration of study participation and for
at least 28 days after treatment has ended.
- Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening.
Ophthalmological Sub-study Exclusion criteria:
1.Presence of any active ocular conditions with or without visual impairment due to any causes (e.g. wet-aged macular degeneration, pathologic myopia, cataract, chorioretinal macular lesion, amblyopia, active diabetic retinopathy, uncontrolled glaucoma, active inflammation or infection, etc.) in one eye or both eyes at the screening phase that may interfere with the ocular assessments or analyses and interpretation of the results from this study, in the clinical judgment of the investigator.
2.Planned ocular treatment (e.g. intravitreal antivascular growth factor, corticosteroids) or surgery during the study period.
3.Current or planned use of ocular or systemic corticosteroids
4.Current or planned use of medications known to be toxic to the retina, lens, optic nerve (e.g. choroquine/hydrochoroquine, chlorpromazine, tamoxifen, desferoximine, etc.). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. The change from baseline in ADAS-Cog11 (Alzheimer’s Disease Assessment Scale-
Cognitive subscale 11 item) total score after 12 weeks of treatment
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1. Change from baseline in the ADCS-ADL (Alzheimer’s Disease Cooperative Study/Activities of Daily Living) score after 12weeks of treatment
2. CIBIC+ (Clinician's Interview-Based Impression of Change) score after 12 weeks of treatment |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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 | 60 |
| 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 |
| Canada |
| Finland |
| France |
| Germany |
| Greece |
| Hungary |
| Italy |
| Japan |
| Norway |
| Spain |
| United Kingdom |
| United States |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 15 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
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