Alzheimer Disease Proof of Concept Study with BI 409306 versus Placebo

Phase 1

Conditions: 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: 18.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2013-005031-24-GB

Lead Sponsor: Boehringer Ingelheim Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 504

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

-Patients who have not received prescribed drugs for treatment of AD (including acetyl cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, phenserine) and Memantine within three 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 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

-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 screening then a CCT or MRI needs to be performed at screening.

-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 mild cognitive impairment within three months prior to screening. Having received active treatment in any other study targeting disease modification like Aß 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 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

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. A combination of male condom with either cap, diaphram or sponge with spermicide (double barrier methods) are considered acceptable, but not highly effective, birth control methods. Note: sexual abstinence is considered a highly effective method only if defined as refraining from hetrosexual intercourse during the entire period of risk associated with the study treatments. Th

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);<br> 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> ;<br> Timepoint(s) of evaluation of this end point: 1: 12 weeks<br>

Secondary Outcome Measures

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

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