Alzheimer Disease Proof of Concept Study with BI 409306 versus Placebo

Phase 1

Conditions: Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
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
MedDRA version: 17.1Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 100000004852

Registration Number: EUCTR2013-005031-24-IT

Lead Sponsor: Boehringer Ingelheim Italia S.p.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1000

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
- Treatment naive patients or 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.
- Patients must have given written informed consent in accordance with Good Clinical Practice (GCP) and local legislation prior to any study procedures. 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, guardian, partner etc.)
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 700
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 300

Exclusion Criteria

-Cognitive impairment with any etiology other than AD (based on
clinical data and/or current laboratory findings and/or a pre-existing MRI or CT of the brain which is not older than 12 months prior to screening visit) for example: neurosyphilis, craniocerebral trauma, small vessel disease
-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 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 drug studies of cognitive
impairment. Currently ongoing treatment with non-prescription
medications, vitamins or other nutritional formulations is allowed
however these should be captured in the electronic case report form (e-CRF)
-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, or a positive urine drug screen for cocaine, heroin, or marijuana.
-Known history 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
-For male patients: 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.
-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
-Known hypersensitivity to the drug product excipients

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess efficacy of different doses of BI 409306 compared to placebo in treatment of Alzheimers' Disease (AD);Secondary Objective: To assess safety and tolerability of different doses of BI 409306 compared to placebo in treatment of Alzheimers' Disease (AD);Primary end point(s): 1: The primary endpoint is Neuropsychological Test Battery (NTB) response, defined as<br>change from baseline in total score after 12-week treatment.<br>;Timepoint(s) of evaluation of this end point: 1: 12 weeks<br>

Secondary Outcome Measures

Name	Time	Method
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.<br>2: Change from baseline in ADCS-ADL (Alzheimer's Disease Cooperative Study/Activities of Daily Living) total score after 12-week treatment.<br>3: Change from baseline CDR-SB (Clinical Dementia Rating, Sum of Boxes) after 12-week treatment<br>4: Change from baseline in ADAS-Cog11 (Alzheimers Disease Assessment Scale cognitive subscale) total score after 12-week treatment.;Timepoint(s) of evaluation of this end point: 1: 12 weeks<br>2: 12 weeks<br>3: 12 weeks<br>4: 12 weeks