Alzheimer DiseasePhase 1NCT01850238
Safety Study of AADvac1, a Tau Peptide-KLH-Conjugate Active Vaccine to Treat Alzheimer's Disease
A Phase 1 study testing AADvac1 in people with Alzheimer Disease, run by Axon Neuroscience SE at 3 sites in Austria.
Trial summary
This first-time-in-man study is mainly designed to assess the safety and tolerability of AADvac1 in the treatment of Alzheimer's disease. 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… Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- AADvac1
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 3 sitesAustria
- Study dates
- May 2013to Mar 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of probable Alzheimer's disease based on the NINCDS/ADRDA criteria.
- MMSE 15-26.
- stable dose of Alzheimer's Disease treatment since 3 months before screening visit or being untreated.
- Hachinski Ischemia Scale ≤ 4.
- MRI consistent with the diagnosis of AD.
- Informed consent capability
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- Written informed consent signed and dated by the patient \& caregiver.
- Age between 50 and 85 years.
- Availability of partner/caregiver.
- Adequate visual and auditory abilities and German language skills for neuropsychological testing.
- Females either surgically sterile or 2+ years postmenopausal.
- Participant on stable doses of all medications for concomitant illnesses according to medical history for at least 30 days prior to Visit 1 if considered relevant by the investigator.
- Sexually active males must be using reliable contraception methods or be surgically sterile.
Who cannot join
- Pregnant women.
- Participation in another clinical trial within 3 months before Visit 1.
- Patients not expected to complete the clinical trial.
- Presence or history of allergy to components of the vaccine, if considered relevant by the investigator.
- Contraindication for MRI imaging (e.g. metallic endoprosthesis, stent implantation in the last 6 months).
- Any of the following detected by brain MRI:
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- Thromboembolic infarction
- Other focal lesions which may be responsible for the cognitive status of the patient
- More than one lacunar infarct with a diameter of less than 1.5 cm in any dimension
- Any lacunar infarct in a strategically important location such as the thalamus, hippocampus of either hemisphere, head of the left caudate
- White matter lesions involving more than 25% of the hemispheric white matter
- Surgery (under general anaesthesia) within 3 months prior to study entry and scheduled surgery during the whole study period.
- History and/or presence of autoimmune disease, if considered relevant by the investigator.
- Recent (≤3 years since last specific treatment) history of cancer (Exceptions: basal cell carcinoma, intraepithelial cervical neoplasia).
- Active infectious disease (e.g., Hepatitis B, C).
- Presence and/or history of Immunodeficiency (e.g., HIV).
- Significant systemic illness, if considered relevant by the investigator.
- Hypothyroidism (patients with corrected hypothyroidism are eligible for the study if treatment has been stable for 3 months before study entry)
- History of significant psychiatric illness such as schizophrenia, bipolar affective disorder or major depression.
- Current depressive episode (Geriatric Depression Scale GDS >5 at Visit 1).
- Metabolic or toxic encephalopathy or dementia due to a general medical condition.
- Alcoholism or substance abuse within the past year (alcohol or drug intoxication).
- Wernicke's encephalopathy
- History or evidence of any other CNS disorder that could be the cause of dementia (infectious or inflammatory/demyelinating CNS conditions, Creutzfeldt-Jakob disease, Parkinson's disease, Huntington's disease, brain tumour, subdural haematoma, etc.)
- History or evidence of cerebrovascular disease (ischemic or haemorrhagic stroke, transient ischemic attack), or diagnosis of possible, probable or definite vascular dementia.
- Epilepsy.
- Prior and/or current treatment with experimental immunotherapeutics including IVIG or any vaccines for AD.
- Current treatment with immunosuppressive drugs.
- Change in dose of standard treatments for AD or hypothyroidism within 3 months prior to visit 1.
- Change in dose of previous and current medications which the patient is taking because of consisting illnesses according medical history within the last 30 days prior to visit 1, if considered clinically relevant by the investigator.
Trial locations and contacts
3 sites in 1 country.
Austria3 sites
Medizinische Universitat Graz
Graz, Styria, 8036
Univeristätsklinik für Neurologie, PMU, Christian-Doppler Klinik
Salzburg, State of Salzburg, 5020
Medizinische Universitat Wien
Vienna, State of Vienna, 1090
About this study
Official title: A 3-months Randomized, Placebo-controlled, Parallel Group, Double-blinded, Multi-centre, Phase I Study to Assess Tolerability & Safety of AADvac1 Applied to Patients With Mild-Moderate Alzheimer's Disease With 3-months Open Label Extension
This first-time-in-man study is mainly designed to assess the safety and tolerability of AADvac1 in the treatment of Alzheimer's disease.
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.
Read the 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). Patients will receive 3 - 6 immunization doses; 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.
- Conditions
- Alzheimer Disease
- Being tested
- AADvac1, Placebo
- Keywords
- Alzheimer disease, tau protein, neurofibrillary degeneration, disease-modifying
- Medical subject headings
- Alzheimer Disease, Frontotemporal Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AADvac1Biological
Also called (no commercial or INN name assigned yet)
AADvac1 is intended as an active vaccination for disease-modifying treatment of Alzheimer's disease.
PlaceboOther
Also called (no other names)
The placebo contains the same buffer and adjuvant as AADvac1, but lacks the API.
| Study group | Role | What they receive |
|---|---|---|
| Placebo (adjuvant in saline solution) | Placebo comparator | Placebo patients will receive 1 dose of placebo per month over 3 months, for a total of 3 administrations.
Placebo consists of vaccine adjuvant in saline solution. Placebo is administered subcutaneously. Receives: Other: Placebo |
| AADvac1 | Experimental | AADvac1 patients will receive 1 dose of AADvac1 per month over 3 months, for a total of 3 administrations.
AADvac1 is a vaccine (single-use vials with solution ready for injection) AADvac1 is administered subcutaneously. Receives: Biological: AADvac1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Tolerability & safety are assessed over a period of 3 months / 3 administrations
Secondary outcomes (1)
Immunogenicity of AADvac1
Measurement of:
- Titres of antibodies reactive with AADvac1
- Titres of antibodies reactive with Alzheimer tau protein
- Antibody isotype profiles
Measured: Immune response to the vaccine will be assessed over 3 months / 3 administrations
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2013 (estimated)
- Study startMay 2013
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Axon Neuroscience SE
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Reinhold Schmidt, Professor, Principal investigator, Medizinische Universität Graz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01850238
- Sponsor's protocol ID
- AXON CO 18700
- Other IDs
- 2012-003916-29
- Status last verified
- Oct 2015
- First submitted
- 7 May 2013
- Last updated
- 12 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 30355322Novak 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.
PubMed 27955995Kontsekova E, Zilka N, Kovacech B, Novak P, Novak M. First-in-man tau vaccine targeting structural determinants essential for pathological tau-tau interaction reduces tau oligomerisation and neurofibrillary degeneration in an Alzheimer's disease model. Alzheimers Res Ther. 2014 Aug 1;6(4):44. doi: 10.1186/alzrt278. eCollection 2014.
PubMed 25478017
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 3-months Randomized, Placebo-controlled, Parallel Group, Double-blinded, Multi-centre, Phase I Study to Assess Tolerability & Safety of AADvac1 Applied to Patients With Mild-Moderate Alzheimer's Disease With 3-months Open Label Extension
- ClinicalTrials.gov ID
- NCT01850238
- Acronym / sponsor ID
- AXON CO 18700
- Conditions
- Alzheimer Disease
- Keywords
- Alzheimer disease, tau protein, neurofibrillary degeneration, disease-modifying
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Axon Neuroscience SEIndustry (pharma, biotech, devices)
- Study start
- May 2013
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 9 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This first-time-in-man study is mainly designed to assess the safety and tolerability of AADvac1 in the treatment of Alzheimer's disease.
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). Patients will receive 3 - 6 immunization doses; 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo (adjuvant in saline solution) | Placebo comparator | Other: PlaceboPlacebo patients will receive 1 dose of placebo per month over 3 months, for a total of 3 administrations. Placebo consists of vaccine adjuvant in saline solution. Placebo is administered subcutaneously. |
| AADvac1 | Experimental | Biological: AADvac1AADvac1 patients will receive 1 dose of AADvac1 per month over 3 months, for a total of 3 administrations. AADvac1 is a vaccine (single-use vials with solution ready for injection) AADvac1 is administered subcutaneously. |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Diagnosis of probable Alzheimer's disease based on the NINCDS/ADRDA criteria.
- MMSE 15-26.
- stable dose of Alzheimer's Disease treatment since 3 months before screening visit or being untreated.
- Hachinski Ischemia Scale ≤ 4.
- MRI consistent with the diagnosis of AD.
Key exclusion criteria (30 listed)
- Pregnant women.
- Participation in another clinical trial within 3 months before Visit 1.
- Patients not expected to complete the clinical trial.
- Presence or history of allergy to components of the vaccine, if considered relevant by the investigator.
- Contraindication for MRI imaging (e.g. metallic endoprosthesis, stent implantation in the last 6 months).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AADvac1Also: (no commercial or INN name assigned yet)AADvac1 is intended as an active vaccination for disease-modifying treatment of Alzheimer's disease. | Biological | AADvac1 |
| PlaceboAlso: (no other names)The placebo contains the same buffer and adjuvant as AADvac1, but lacks the API. | Other | Placebo (adjuvant in saline solution) |
Primary outcome
Tolerability and safety profile of AADvac1 in patients with mild-to-moderate Alzheimer's disease
Time frame: Tolerability & safety are assessed over a period of 3 months / 3 administrations
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
1 secondary outcome
Immunogenicity of AADvac1
Time frame: Immune response to the vaccine will be assessed over 3 months / 3 administrations
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2015.
- Derived from this study: PubMed 30355322Novak 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.
- Derived from this study: PubMed 27955995Novak 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.
- Derived from this study: PubMed 25478017Kontsekova E, Zilka N, Kovacech B, Novak P, Novak M. First-in-man tau vaccine targeting structural determinants essential for pathological tau-tau interaction reduces tau oligomerisation and neurofibrillary degeneration in an Alzheimer's disease model. Alzheimers Res Ther. 2014 Aug 1;6(4):44. doi: 10.1186/alzrt278. eCollection 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Reinhold Schmidt, Professor principal investigator
Medizinische Universität Graz
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AADvac1 in people with Alzheimer Disease, run by Axon Neuroscience SE at 3 sites in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tolerability and safety profile of AADvac1 in patients with mild-to-moderate Alzheimer's disease (time frame: Tolerability & safety are assessed over a period of 3 months / 3 administrations). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01850238, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2015.