Tolerability and Safety of Subcutaneous Administration of AFFITOPE AD02 in Mild to Moderate Alzheimer's Disease

October 18, 2010 updated by: Affiris AG

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 AD02 Applied With or Without Adjuvant to Patients With Mild to Moderate Alzheimer's Disease

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Vienna, Austria, A-1010
        • Ordination Univ. Doz. Dr. Margot Schmitz

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

48 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Main Inclusion Criteria:

  • Diagnosis of probable Alzheimer's disease based on the NINCDS/ADRDA criteria.
  • Alzheimer's disease of mild to moderate degree (MMSE 16-26)
  • Magnetic Resonance Imaging scan (MRI) of brain consistent with diagnosis of AD.
  • Written informed consent signed and dated by the patient and the caregiver.
  • Age 50-80 years.
  • Availability of a partner/caregiver

Other Inclusion Criteria apply.

Main Exclusion Criteria:

  • Presence or history of allergy to components of the vaccine.
  • Contraindication for MRI imaging.
  • Participation in another clinical trial.
  • Prior and/or current treatment with experimental immunotherapeutics including IVIG or vaccines for AD.
  • Prior and/or current treatment with immunosuppressive drugs
  • History and/or presence of autoimmune disease.

Other Exclusion Criteria apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
AFFITOPE AD02 without adjuvant
4 subcutaneous injections of IP in 4-week intervals
Active Comparator: 2
AFFITOPE AD02 with adjuvant
4 subcutaneous injections of IP in 4-week intervals

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Tolerability
Time Frame: 1 year
1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
Immunological and clinical efficacy (evaluated in explorative manner)
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Margot Schmitz, Univ. Doz. Dr., Ordination Univ. Doz. Dr. Margot Schmitz

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2008

Primary Completion (Actual)

September 1, 2009

Study Completion (Actual)

September 1, 2009

Study Registration Dates

First Submitted

March 5, 2008

First Submitted That Met QC Criteria

March 5, 2008

First Posted (Estimate)

March 12, 2008

Study Record Updates

Last Update Posted (Estimate)

October 19, 2010

Last Update Submitted That Met QC Criteria

October 18, 2010

Last Verified

October 1, 2010

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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