A study comparing the safety and effects of a compound ACI-91 with placebo in patients with mild to moderate Alzhiemer's disease

• Conditions: Mild to moderate Alzheimer’s Disease; MedDRA version: 14.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

• Registration Number: EUCTR2008-005260-14-DE
• Lead Sponsor: AC Immune SA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-09-15
• Last Update Posted: 24 July 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

- Patients with a documented diagnosis of probable Alzheimer’s Disease” according to NINDS-ADRDA criteria supported by the results of a brain MRI scan made within one year of screening
- Patients with MMSE 18 – 26 at screening
- Male and female patients of age 40-85 years
- Patients cared for by a reliable caregiver either living-in or visiting on a daily basis to assure compliance, assist with clinical assessments to make sure that safety issues are reported
- Women must be post-menopausal for at least one year, surgically sterilised or using reliable contraceptive measures, eg. oral contraceptive or double-barrier method
- Patients who in the opinion of the investigator are likely to cooperate with the requirements of the study, able to hear, see and speak adequately to conduct the assessments and able to swallow the study medication
- Patients receiving stable dose of acetylcholinesterase inhibitors for at least 4 months prior to screening.
- Patients and caregivers must be fluent in German and able to comply with all study procedures
- Patients giving written informed consent (ability to give consent).

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 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 46

Exclusion Criteria

- Clinically significant abnormalities of clinical haematology or biochemistry including, but not limited to, elevations greater than 1.5 times the upper limit of normal of SGOT, SGPT or creatinine
- Patients with elevated prothrombin or partial thromboplastin time
- Patients with a major depressive episode within the past 2 years or a history of recurrent major depression or a history of bipolar disorders according to DSM-IV criteria
- Patients with a Hamilton Depression (17 Item) Scale total score of 14 or greater or an individual item score of 3 or greater on Depressed Mood, Feelings of Guilt or Suicide at screening.
- Past or present history of abuse of drugs or alcohol
- Patients with stroke or myocardial infarction within the past year
- Participation in a trial of another investigational drug within the last three months prior to screening
- Patients with other medical conditions which may influence cognitive performance e.g. Parkinson’s disease, normal pressure hydrocephalus, progressive supranuclear palsy brain tumor, recurrent seizures, subdural hematoma, multiple sclerosis, severe head injury with coma lasting for more than a day
- Patients with an alternative cause for dementia as determined by MRI scan within 1 year prior to the study, at a time when the patient was known to be demented. Diffuse periventricular white matter changes need not result in exclusion.
- Patients with vascular dementia according to NINDS-AIREN criteria
- Patients with Vitamin B12 or folate deficiency or hypothyroidism unless on replacement therapy for at least three months.
- Patients with a positive HIV and/or syphilis test at screening
- Patients with closed angle glaucoma
- Patients with symptomatic prostatic hypertrophy
- Patients with any unstable medical condition which might alter the ability to complete the clinical study.
- Patients with moderate or severe renal or hepatic impairment
- Patients unable to undergo MRI examination for any reason, including claustrophobia
- Patients who are lactating, pregnant or planning to be pregnant, or who have a positive pregnancy test at screening (women of childbearing potential)
- Patients receiving anticoagulant drugs
- Patients receiving anticholinergic drugs, eg oxybutinin, tolteridone, tricyclic antidepressants
- Patients receiving neuroleptic drugs other than atypical antipsychotics
- Patients receiving pirenzepine
- Patients receiving antioxidants including Coenzyme Q10 or high dose vitamins (5 times the recommended dose of Vitamin E or Vitamin C)
- Patients receiving MAO-A or MAO-B inhibitors eg selegiline, rasagiline
- Patients receiving putative cognitive enhancers other than acetylcholinesterase inhibitors (eg ergoloid mesylates, nimodipine, piracetam, gingko biloba).
- Patients receiving memantine currently or previously
- Patients with a major psychiatric illness within the past 5 years
- Patients who have been hospitalized involuntarily or at the request of the caregiver

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess safety, tolerability including examination for potential negative effects on cognition of 12-month treatment with ACI-91 in patients with mild to moderate AD receiving a stable dose of an acetylcholinesterase inhibitor;Secondary Objective: - To assess the biochemical effects of ACI-91 on biomarkers of Alzheimer’s disease including, amyloid ß (Aß1-42 and Aß1-40), F2-isoprostanes, total tau and phosphotau, and BACE-1,<br>- To explore the effects of ACI-91 on cognition, global function, activities of daily living and neuropsychiatric symptoms<br>- To assess the plasma levels of ACI-91<br>;Primary end point(s): Safety/tolerability:<br>General: Adverse events, physical (including vital signs) and neurological examination, ECG, routine blood and urine analyses, global assessment of tolerability as well as cognitive assessment.;Timepoint(s) of evaluation of this end point: Timepoints Safety: 0, 4, 12, 24, 36, 52 and 56 weeks.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Efficacy (Biochemical):<br>- Plasma levels of Aß1-42 and Aß1-40<br>- CSF levels of Aß1-42 and Aß1-40<br>- CSF levels of F2-isoprostane<br>- CSF levels of tau and phosphotau<br>- CSF levels of BACE-1<br><br>Efficacy (Clinical):<br>- Change from baseline in cognition assessed by the MMSE, the Neuropsychological Test Battery (NTB) and Alzheimer's Disease Assessment Scale cognitive subpart (ADAS-cog)<br>- Change from baseline in global function assessed by the Clinical Dementia Rating Scale (CDR) sum of boxes<br>- Change from baseline in Activities of Daily Living (ADL) assessed by the Disability Assessment in Dementia Scale (DAD)<br>- Change from baseline in neuropsychiatric symptoms assessed by the Neuropsychiatric Inventory Scale (NPI)<br><br>Pharmacokinetics:<br>- Plasma levels of ACI-91: sparse sampling at week 0, 12 and 52 in all subjects;Timepoint(s) of evaluation of this end point: Timepoints Efficacy: 0, 12, 24, 36, 52 and 56 weeks.