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18-months Safety Follow-up Study of AADvac1, an Active Tau Vaccine for Alzheimer's Disease (FUNDAMANT)

Primary Purpose

Alzheimer's Disease

Status

Completed

Phase

Phase 1

Locations

Austria

Study Type

Interventional

Intervention

AADvac1

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring Alzheimer's disease, tau, dementia, elderly, cognitive, disease modifying, treatment, immunization, vaccine

Eligibility Criteria

50 Years - 86 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Completion of visit V8 of the AADvac1 phase I study AXON CO 18700 (EUDRACT 2012-003916-29).
Informed consent capability (as determined by an independent neurologist/psychiatrist).
Written informed consent signed and dated by the patient and the caregiver.
Availability of a partner/caregiver knowing the patient and being able to accompany the patient to the visits
Adequate visual and auditory abilities and language skills to allow neuropsychological testing.
Female patients are only eligible for the study if they are either surgically sterile or at least 2 years postmenopausal.
Sexually active males must be using reliable contraception methods (i.e. condoms) or be surgically sterile.

Exclusion Criteria:

Pregnant women.
Participation in another clinical trial during the course of this study.
Contraindication for MRI imaging such as MRI-incompatible metallic endoprosthesis or MRI-incompatible stent implantation
History and/or presence of autoimmune disease, if considered relevant by the investigator.
Significant systemic illness (e.g., chronic renal failure, chronic liver disease, poorly controlled diabetes, poorly controlled congestive heart failure, congenital long QT syndrome, other deficiencies), if considered relevant by the investigator.
Current treatment with immunosuppressive drugs.

Sites / Locations

Medizinische Universitat Graz
Univeristätsklinik für Neurologie, PMU, Christian-Doppler Klinik
Medizinische Universitat Wien
Sozialmedizinisches Zentrum Ost (SMZ Ost) /Donauspital, Memory Clinic and Karl Landsteiner Institut for Amnestic disorders

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AADvac1

Arm Description

Patients who have received 6 doses in the previous trial will be administered 1-2 booster doses of AADvac1 (2 if their antibody titers decline below those achieved in the previous trial). Patients who have received 3 doses in the previous trial will be administered another 3 doses, then vaccinated with booster doses as above.

Outcomes

Primary Outcome Measures

Tolerability and safety profile of AADvac1 in patients with mild-to-moderate Alzheimer's disease

Safety is assessed via recording of all Adverse Events and Adverse Events Patients are observed via: MRI Clinical & neuro-psychiatric observation Cognitive testing ECG Blood biochemistry, hematology, coagulation measurement Urine analysis

Secondary Outcome Measures

Immunogenicity of AADvac1

Measurement of: Titres of antibodies reactive with AADvac1 Titres of antibodies reactive with Alzheimer tau protein Antibody isotype profiles

Patient cognition

Tests used: ADAS-Cog (Alzheimer's Disease Assessment Scale-cognitive subscale) COWAT (Controlled oral word association test) Category fluency

Full Information

NCT ID

NCT02031198

First Posted

January 7, 2014

Last Updated

March 15, 2017

Sponsor

Axon Neuroscience SE

1. Study Identification

Unique Protocol Identification Number

NCT02031198

Brief Title

18-months Safety Follow-up Study of AADvac1, an Active Tau Vaccine for Alzheimer's Disease

Acronym

FUNDAMANT

Official Title

An 18-months Open Label Phase I Follow-up Study on Patients With Alzheimer's Disease Who Have Completed the AADvac1 Phase I Study "AXON CO 18700"

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Completed

Study Start Date

January 2014 (undefined)

Primary Completion Date

August 2016 (Actual)

Study Completion Date

December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Axon Neuroscience SE

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This follow-up study continues to observe patients who have completed the phase 1 trial of AADvac1, for another 18 months. Long-term safety and behavior of the immune response to AADvac1 over time are the main points of interest. AADvac1 is a vaccine directed against pathologically modified Alzheimer tau protein that is the main constituent of neurofibrillary tangles (NFTs), and is intended to be a disease-modifying treatment for Alzheimer's disease, i.e. to halt its progress. As this study is a Phase I study focused on tolerability and safety, efficacy will be assessed in an exploratory manner.

Detailed Description

AADvac1 is a candidate therapeutic vaccine for Alzheimer's disease that targets misfolded tau protein, a common denominator of neurofibrillary pathology. Based on preclinical results, the intervention is expected to reduce the number of neurofibrillary tangles, remove hyperphosphorylated tau protein and reduce the amount of oligomerized and insoluble pathological tau in the brain, to halt the spread of neurofibrillary pathology through the brain, and thus prevent associated cognitive decline. The vaccine's antigenic determinant is a synthetic peptide derived from a tau protein sequence, which is coupled to keyhole limpet hemocyanin (KLH) and uses aluminum hydroxide (Alhydrogel) as an adjuvant. At present AADvac1 is intended as an active immunotherapy for patients with diagnosed Alzheimer's disease (AD). According to need, patients will receive additional immunization doses beyond those administered in the preceding pase 1 trial; the raised titers of therapeutic antibodies and possible benefits of the treatment can extend beyond the duration of the study. Because of the central role of pathological misfolded tau protein in the etiology of AD, the vaccine is expected to be more effective than active or passive immunotherapies aiming to eliminate the amyloid β plaques that have been clinically investigated so far.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer's Disease

Keywords

Alzheimer's disease, tau, dementia, elderly, cognitive, disease modifying, treatment, immunization, vaccine

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AADvac1

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

AADvac1

Other Intervention Name(s)

Axon peptide 108 (coupled to KLH), 40ug/0.3mL, Axon peptide 108 conjugated to KLH

Intervention Description

Active immunization against pathological Alzheimer's disease tau protein

Primary Outcome Measure Information:

Title

Tolerability and safety profile of AADvac1 in patients with mild-to-moderate Alzheimer's disease

Description

Time Frame

Tolerability & safety are assessed over a period of 18+ months

Secondary Outcome Measure Information:

Title

Immunogenicity of AADvac1

Description

Measurement of: Titres of antibodies reactive with AADvac1 Titres of antibodies reactive with Alzheimer tau protein Antibody isotype profiles

Time Frame

Immune response to the vaccine will be assessed over 18 month

Title

Patient cognition

Description

Tests used: ADAS-Cog (Alzheimer's Disease Assessment Scale-cognitive subscale) COWAT (Controlled oral word association test) Category fluency

Time Frame

18+ months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

86 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Completion of visit V8 of the AADvac1 phase I study AXON CO 18700 (EUDRACT 2012-003916-29). Informed consent capability (as determined by an independent neurologist/psychiatrist). Written informed consent signed and dated by the patient and the caregiver. Availability of a partner/caregiver knowing the patient and being able to accompany the patient to the visits Adequate visual and auditory abilities and language skills to allow neuropsychological testing. Female patients are only eligible for the study if they are either surgically sterile or at least 2 years postmenopausal. Sexually active males must be using reliable contraception methods (i.e. condoms) or be surgically sterile. Exclusion Criteria: Pregnant women. Participation in another clinical trial during the course of this study. Contraindication for MRI imaging such as MRI-incompatible metallic endoprosthesis or MRI-incompatible stent implantation History and/or presence of autoimmune disease, if considered relevant by the investigator. Significant systemic illness (e.g., chronic renal failure, chronic liver disease, poorly controlled diabetes, poorly controlled congestive heart failure, congenital long QT syndrome, other deficiencies), if considered relevant by the investigator. Current treatment with immunosuppressive drugs.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Reinhold Schmidt, Professor

Organizational Affiliation

Medizinische Universität Graz

Official's Role

Principal Investigator

Facility Information:

Facility Name

Medizinische Universitat Graz

City

Graz

State/Province

Steiermark

ZIP/Postal Code

8036

Country

Austria

Facility Name

Univeristätsklinik für Neurologie, PMU, Christian-Doppler Klinik

City

Salzburg

ZIP/Postal Code

5020

Country

Austria

Facility Name

Medizinische Universitat Wien

City

Wien

ZIP/Postal Code

1090

Country

Austria

Facility Name

Sozialmedizinisches Zentrum Ost (SMZ Ost) /Donauspital, Memory Clinic and Karl Landsteiner Institut for Amnestic disorders

City

Wien

ZIP/Postal Code

A-1220

Country

Austria

12. IPD Sharing Statement

Citations:

PubMed Identifier

30355322

Citation

Novak P, Schmidt R, Kontsekova E, Kovacech B, Smolek T, Katina S, Fialova L, Prcina M, Parrak V, Dal-Bianco P, Brunner M, Staffen W, Rainer M, Ondrus M, Ropele S, Smisek M, Sivak R, Zilka N, Winblad B, Novak M. FUNDAMANT: an interventional 72-week phase 1 follow-up study of AADvac1, an active immunotherapy against tau protein pathology in Alzheimer's disease. Alzheimers Res Ther. 2018 Oct 24;10(1):108. doi: 10.1186/s13195-018-0436-1.

Results Reference

derived

PubMed Identifier

27955995

Citation

Novak P, Schmidt R, Kontsekova E, Zilka N, Kovacech B, Skrabana R, Vince-Kazmerova Z, Katina S, Fialova L, Prcina M, Parrak V, Dal-Bianco P, Brunner M, Staffen W, Rainer M, Ondrus M, Ropele S, Smisek M, Sivak R, Winblad B, Novak M. Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Neurol. 2017 Feb;16(2):123-134. doi: 10.1016/S1474-4422(16)30331-3. Epub 2016 Dec 10.

Results Reference

derived

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18-months Safety Follow-up Study of AADvac1, an Active Tau Vaccine for Alzheimer's Disease

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