Clinical trial NCT00411580: Safety and Tolerability Study in Patients With Mild to Moderate Alzheimer's Disease (AD)
Official title: A 52-week, Multi-center, Randomized, Double-blind, Placebo-controlled, Time-lagged, Parallel Group Study in Patients With Mild to Moderate Alzheimer's Disease (AD) to Investigate the Safety, Tolerability and Aß-specific Antibody Response Following Three Subcutaneous Injections of CAD106
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Keywords: Mild, moderate Alzheimer's Disease (AD), Aß-specific antibody, CAD106
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2006-12-14
Enrollment: 58
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety and tolerability and Aß-specific antibody response of CAD106 in patients with mild to moderate Alzheimer's Disease.

Patients also had a 2 year follow-up to assess disease progression where no drug was administered.


Eligibility criteria: Inclusion Criteria:

* males and/or females patients between 50 to 80 years of age (both inclusive).
* female patients must be without childbearing potential (post-menopausal or surgically sterilized).
* diagnosis of dementia of the Alzheimer's type according to the DSM-IV criteria (Diagnostic and Statistical Manual of Mental Disorders, 4th edition).
* mild to moderate AD as confirmed by Mini-Mental State Exam score of 16 to 26 (both inclusive) at screening.
* able to provide written informed consent and having a responsible caregiver that can provide written assent prior to study participation. For patients who have been declared mentally incompetent, a legal representative will need to provide informed consent on their behalf.

Exclusion Criteria:

* previously participated in an AD vaccine study and received active treatment
* history or presence of an active autoimmune and/or cerebrovascular disease
* history or presence of seizures, with an acute or chronic inflammation
* clinically relevant atopic condition, who suffer from an other neurodegenerative disease and/or psychiatric disorders (with the exception of successfully treated depression)
* immunosuppressive treatment including systemic steroids
* obtained a vaccination (e.g. against influenza) within 4 weeks before the first study drug injection
* advanced, severe, progressive or unstable disease that might interfere with the safety of the patient
* started treatment with psychotropic medication within 3 months (4 weeks for SSRIs and other newer antidepressants without anticholinergic properties) prior to randomization with the exception of mild hypnotic drugs (e.g. zolpidem, zopiclone, oxazepam) and low doses of neuroleptic drugs (e.g. up to 2 mg risperidone).

Patients, who are on stable treatment with cholinesterase-inhibitors (ChEIs) and/or memantine for at least 3 months, and/or with SSRIs and/or other newer antidepressants (without anticholinergic properties) for at least 4 weeks before randomization, can be included into the study.

Primary outcomes:
measure: Tolerability/safety assessments (physical/neurol.exam., ECG, vital signs, standard and special immunological laboratory evaluations, MRIs, EEGs, AE/SAE monitoring).
timeFrame: at multiple timepoints including but not limited to screening, baseline, and through the end of the study to Week 52.
measure: Antibody titers (IgM and IgM titers against amyloid and carrier protein).
timeFrame: at multiple timepoints including but not limited to baseline and through the end of the study to Week 52
Secondary outcomes:
measure: Immune response, cognitive and functional assessments
timeFrame: at multiple timepoints including but not limited to baseline and through the end of the study to Week 52
Other outcomes:
Locations:
city: Malmo
country: Sweden
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
affiliation: Investigator site
name: Novartis
role: PRINCIPAL_INVESTIGATOR
References:
citation: Winblad B, Andreasen N, Minthon L, Floesser A, Imbert G, Dumortier T, Maguire RP, Blennow K, Lundmark J, Staufenbiel M, Orgogozo JM, Graf A. Safety, tolerability, and antibody response of active Abeta immunotherapy with CAD106 in patients with Alzheimer's disease: randomised, double-blind, placebo-controlled, first-in-human study. Lancet Neurol. 2012 Jul;11(7):597-604. doi: 10.1016/S1474-4422(12)70140-0. Epub 2012 Jun 6.