Tolerability and Safety of Subcutaneous Administration of Affitope AD01 in Mild to Moderate Alzheimer's Disease
|ClinicalTrials.gov Identifier: NCT00495417|
Recruitment Status : Completed
First Posted : July 3, 2007
Last Update Posted : October 19, 2010
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer's Disease||Biological: AFFITOPE AD01 Biological: AFFITOPE AD01 adjuvanted||Phase 1|
Alzheimer's Disease (AD) is a devastating neurodegenerative disorder for which there is no cure.
Although the etiology of AD is not fully understood, recent research suggests that Aβ is central to the disease process. Consequently, approaches capable of removing Aβ from the brain, such as Aβ immunotherapy, are expected to possess disease-modifying potential. This view is supported by evidence gathered in mouse models of AD and studies involving AD patients.
Based on the view that active Aβ immunotherapy has disease-modifying potential both in animal models of AD and in patients, and on the knowledge gathered on the side-effects of Aβ-based immunotherapy encountered in humans, we designed a new generation of AD vaccines. Rather than using full length Aβ itself, we choose to use mimotopes of the N-terminal end of Aβ as the antigenic component of our vaccine (Mimotopes discovered by Affiris GmbH have been termed Affitopes). Mimotopes are peptides that functionally mimic the native antigenic epitope but do not show sequence identity to it. Thus, while being different from the original antigen, mimotopes are recognized by the same antibodies and, vice versa, are capable of inducing antibodies that cross-react with the original antigen itself. A major advantage offered by mimotopes is the lack of tolerance mechanisms that would prevent the induction of an immune response to it (as is the case with self peptides/proteins such as Aβ). To further increase the vaccine's safety profile, the length of the mimotope used was limited to preclude the elicitation of Aβ-specific T cells. Also, the mimotope used has been designed to generate antibodies directed exclusively to Aβ (i.e., they do not recognize parental APP itself). To provide helper epitopes for the generation of an antibody response, the mimotope is coupled to a carrier.
The trial is designed as a patient-blinded, single-center, randomized, controlled, parallel group, phase I clinical study of repeated once every 4 weeks administration by subcutaneous injection of Affitope AD01 alone or adsorbed to aluminum hydroxide in 24 patients with mild to moderate Alzheimer's Disease. In total, each patient will receive 4 immunizations. Patients will be randomized to receive Affitope AD01 alone or adsorbed to aluminum hydroxide. Each treatment group consists of 12 patients. For safety reasons, inclusion of patients will be done in a stepwise manner.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||Randomized, Controlled, Parallel Group, Patient-blinded, Single-center Phase I Pilot Study to Assess Tolerability and Safety of Repeated s.c. Administration of a Single-dose of Affitope AD01 Applied With or Without Adjuvant to Patients With Mild to Moderate Alzheimer's Disease|
|Study Start Date :||July 2007|
|Actual Primary Completion Date :||August 2009|
|Actual Study Completion Date :||August 2009|
|Active Comparator: 1||
Biological: AFFITOPE AD01
|Active Comparator: 2||
Biological: AFFITOPE AD01 adjuvanted
- Tolerability [ Time Frame: One year ]
- Immunological and clinical efficacy (evaluated in explorative manner) [ Time Frame: One year ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00495417
|Department of Clinical Pharmacology, Medical University of Vienna|
|Vienna, Austria, 1090|
|Principal Investigator:||Markus Müller, UnivProf.Dr.||Medical University of Vienna|