Tolerability and Safety of Subcutaneous Administration of AFFITOPE AD02 in Mild to Moderate Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to assess the tolerability and safety of repeated subcutaneous
      injection of a single dose of AFFITOPE AD02 in patients with mild to moderate Alzheimer's
      Disease.
    

Detailed description: 
      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 AD02 alone or adsorbed to aluminium 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 AD02 alone or adsorbed to alumimium
      hydroxide. Each treatment group consists of 12 patients. For safety reasons, inclusion of
      patients will be done in a stepwise manner.
    

Intervention name(s): AFFITOPE AD02
Intervention type(s): Biological
Intervention description(s): 4 subcutaneous injections of IP in 4-week intervals
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Alzheimer; Morbus Alzheimer; Alzheimer Vaccine; Vaccine; AD; Aβ immunotherapy