A 90-week, multi-center, randomized, double-blind, placebo-controlled study in patients with mild Alzheimer s Disease (AD) to investigate the safety, tolerability and Abeta-specific antibody response following repeated i.m. injections of adjuvanted CAD106 - ND

• Register: EUCTR
• Last refreshed on: 7 January 2013
• Main ID: EUCTR2009-012394-35-IT
• Date of registration: 17/02/2010
• Prospective Registration: No
• Primary sponsor: NOVARTIS FARMA
• Public title: A 90-week, multi-center, randomized, double-blind, placebo-controlled study in patients with mild Alzheimer s Disease (AD) to investigate the safety, tolerability and Abeta-specific antibody response following repeated i.m. injections of adjuvanted CAD106 - ND
• Scientific title: A 90-week, multi-center, randomized, double-blind, placebo-controlled study in patients with mild Alzheimer s Disease (AD) to investigate the safety, tolerability and Abeta-specific antibody response following repeated i.m. injections of adjuvanted CAD106 - ND
• Date of first enrolment: 02/02/2010
• Target sample size: 120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012394-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: - same IMP used at different dosage

Countries of recruitment

Belgium, Germany, Italy, Netherlands, Spain, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
Patients have to meet all of the following criteria at Screening to enter into the study: 1. Written informed consent obtained before any assessment is performed according to local requirements for obtaining consent in mild AD patients (see Section 10.2). 2. Male and female patients below the age of 85 years. 3. Female patients must be without childbearing potential (post-menopausal or surgically sterilized). If sterilized, female patients must have been surgically sterilized at least 6 months prior to screening. Surgical sterilization procedures must be supported with clinical documentation made available to the Novartis Monitor and noted in the Relevant Medical History / Current Medical Conditions section of the eCRF. OR: Postmenopausal women must have no regular menstrual bleeding for at least 1 year prior to inclusion as documented in the patient s records. 4. Diagnosis of dementia of the Alzheimer s type according to the DSM-IV criteria (Diagnostic and Statistical Manual of Mental Disorders, 4th edition). 5. Patients who satisfy the criteria for a clinical diagnosis of probable AD established by a Work Group of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer s Disease and Related Disorders Association (NINCDSADRDA). 6. Mild AD as confirmed by a MMSE score of 20 to 26 (both inclusive) at screening, and either untreated or on stable dose of cholinesterase inhibitor and/or other AD treatment over the last 4 weeks prior to the clinical assessments. 7. Sufficient education to have been able to read, write, and communicate effectively during the pre-morbid state (e.g. completion of at least 6 years of regular schooling or sustained employment). 8. Cooperative, willing to complete all aspects and attend all visits of the study including lumbar puncture/CSF samplings (primarily for safety reasons), and capable of doing so, either alone or with the aid of a responsible caregiver. 9. Residing with someone in the community throughout the study or, if living alone, who have daily contact with a primary caregiver. 10. Primary caregiver is present and willing to assent in writing to taking the responsibility for assessing the condition of the patient throughout the study, and for providing input to safety and tolerability assessments in accordance with all protocol requirements.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients meeting any of the following criteria during Screening or Baseline evaluations (i.e. prior to the time of randomization) will be excluded from randomization into the study: NB. In case of assessments repeated during the Screening period the latest measurements will qualify for the criteria below. Exclusion criteria related to CNS 1. Any medical or neurological condition, other than AD, that contributes significantly to the patient s dementia (e.g., abnormal thyroid function tests, Vitamin B12 or folate deficiency, post-traumatic conditions, Huntington s disease, Parkinson s disease, Lyme s disease, syphilis, HIV dementia), including any CSF and/or brain MRI findings at screening. 2. History in the past two years or current diagnosis of CNS inflammation as indicated by: either MRI findings indicative of meningoencephalitis or another concurrent disease (according to central reader evaluation at screening and clinical judgment); or signs of inflammation in CSF as defined by clinical judgment. In most cases, in a CSF sample not contaminated by blood, this will be shown by >5 leukocytes/μl. 3. Evidence of vascular dementia or other cerebrovascular disease, assessed by investigator and/or MRI central reader, defined as any of the following: one or more large infarct (> 2 cm) or two or more lacunar infarcts (< 2 cm); or confluent white matter lesions, considered likely to contribute to patients dementia; or intracranial aneurysms or hemorrhages, except for up to two cerebral microhemorrhages, defined as a focal T2* hypointensity < 1 cm; or NB. If a MR machine with field strength > 1.5 T is used, higher number of microhemorrhages will be acceptable as defined by the MRI central reader. Hachinski score of > 4 at screening, or any transitory ischemic attack or unexplained loss of consciousness in the past year. 4. Current DSM-IV diagnosis of major depression and/or any other DSM-IV Axis 1 diagnosis that may interfere with the evaluation of the patient s response to study medication, including other primary neurodegenerative dementia, schizophrenia, or bipolar disorder. 5. History or current diagnosis of seizure disorder. Exclusion criteria related to other medical conditions 6. Any advanced, severe, progressive, or unstable disease that may interfere with the safety, tolerability and pharmacodynamic assessments and/or with the antibody titer response in the study or put the patient at special risk (e.g. indication for anticoagulant therapies, Hepatitis B or C, HIV). 7. History or current diagnosis of an active autoimmune disease (e.g. psoriasis, rheumatoid arthritis, Crohn s disease, systemic lupus erythematosus, Type I diabetes mellitus, Hashimoto tyroiditis). 8. Evidence of systemic inflammation as shown by e.g. an elevated CRP above normal range at Screening or fever (i.e. axillary body temperature ≥ 38C (100.4 F)) before dosing on the day of 1st injection, as measured at the site). (NB. In case of positive findings at Screening which are considered to be due to a known transient condition (e.g. common cold, urinary tract infection), the randomization can be postponed until findings have normalized.) 9. Coronary heart disease as shown by: history of myocardial infarction or coronary stent placement within the last year, or current diagnosis of unstable angina pectoris or atherosclerotic coronary artery disease of clinical significance. 10. Symptomatic heart f

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Mild Alzheimer s Disease (AD)
MedDRA version: 12.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease

Intervention(s)

Product Name: Not available yet
Product Code: CAD106A
Pharmaceutical Form: Powder and solvent for solution for injection
Current Sponsor code: CAD106A
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 450-
Pharmaceutical form of the placebo: Powder and solvent for solution for injection
Route of administration of the placebo: Intramuscular use

Primary Outcome(s)

Secondary Objective: To characterize the Aβ- and Qβ-specific antibody response to CAD106 (with Alum or MF59) in serum and CSF, e.g. by measuring Aβ-specific IgMs and Qβ-specific IgGs in serum, and markers of the quality of the immune response. To characterize Aβ-specific and Qβ-specific T-cell response to CAD106 (with Alum or MF59) using PBMCs. To evaluate changes over time of the concentrations of disease related markers (Aβ1-40 and Aβ1-42 in plasma; Aβ1-40, Aβ1-42, total-tau, phospho-tau in CSF, or other markers) in patients with mild AD receiving CAD106 (with Alum or MF59) compared to placebo.

Main Objective: To assess the safety and tolerability of up to 7 repeated injections of CAD106 with Alum or MF59 in patients with mild Alzheimer s Disease (AD) over 90 weeks. To compare the immunogenicity of CAD106 with Alum vs MF59 after up to 7 injections in patients with mild Alzheimer s Disease (AD) as measured by the titers of Aβ-specific IgG in serum across regimens and in reference to non-adjuvanted CAD106.

Primary end point(s): The first primary objective of the study is the assessment of safety and tolerability of CAD106 with Alum or MF59.

Secondary ID(s)

CAD106A2203

2009-012394-35-NL