Primary Progressive Nonfluent AphasiaPhase 1AIDANCT03174886
A 24-month Phase 1 Pilot Study of AADvac1 in Patients With Non Fluent Primary Progressive Aphasia
A Phase 1 study testing AADvac1 40 µg and AADvac1 160 µg in people with Primary Progressive Nonfluent Aphasia, run by Axon Neuroscience SE at 3 sites in Germany.
Trial summary
This study is a pilot trial evaluating the safety and immunogenicity of AADvac1 in patients with the non-fluent variant of Primary Progressive Aphasia. 50% of participants will receive the 40 µg dosage of AADvac1 and 50% of participants will receive the 160 µg dosage of AADvac1. No placebo is used. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Primary Progressive Nonfluent Aphasia
- What is being tested?
- AADvac1 40 µg and AADvac1 160 µg
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 3 sitesGermany
- Study dates
- 31 Jul 2017to Nov 2020
- 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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient has a clinical diagnosis of non-fluent/agrammatic variant PPA according to the criteria by Gorno-Tempini et al. (2011) with evidence of left frontal brain hypometabolism. Patients with right-sided hypometabolism are eligible for the study only if they are left-handed.
- Patient has a FTLD-CDR language domain score of ≤ 2, and other individual FTLD-CDR domain scores ≤ 1.
- Patient's age is 18 - 85 years inclusive at the time of having provided informed consent.
- Patient has adequate visual and auditory abilities and premorbid local language skills to allow neuropsychological testing.
- Sexually active female patients must be using highly effective contraception methods, or be surgically sterile, or be at least 2 years post-menopausal.
- Sexually active male patients must be using highly effective contraception methods, or be surgically sterile.
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- Patient and caregiver have signed and dated written informed consent.
- Availability of a partner/caregiver knowing the patient and being able to accompany the patient to the visits.
- Patient is legally competent.
Who cannot join
- The patient's brain MRI is incompatible with a diagnosis of nfvPPA.
- Patient has a history or evidence of a central nervous system (CNS) disorder other than nfvPPA which may cause symptoms of aphasia or dementia (Alzheimer's disease, Dementia with Lewy Bodies, inflammatory/demyelinating CNS conditions, Creutzfeldt-Jakob disease, Huntington's disease, etc.)
- Patient has a history or currently suffers from a significant psychiatric illness such as schizophrenia, any type of psychotic disorder or bipolar affective disorder.
- Patient has a history or evidence of cerebrovascular disease (ischemic or haemorrhagic stroke), or diagnosis of possible, probable or definite vascular dementia.
- Patient has Wernicke's encephalopathy.
- Patient has metabolic or toxic encephalopathy or dementia due to a general medical condition.
Show all 32Show fewer
- Patient suffers from hypothyroidism, defined as thyroid-stimulating hormone elevation > 5.000 mcIU/mL, and/or fT4 levels < 0.7 ng/dL. Patients with corrected hypothyroidism are eligible for the study provided that treatment has been stable for 12 weeks before study entry.
- Patient has a known pathogenic mutation in GRN or C9orf72.
- Presence or history of allergy to components of the vaccine.
- Presence and/or history of immunodeficiency (e.g., HIV).
- Patient is currently being treated with immunosuppressive drugs.
- Patient has a history and/or currently suffers from a clinically significant autoimmune disease, or is expected to receive immunosuppressive or immunomodulatory treatment at the present or in the future.
- Patient has a recent (≤ 5 years since last specific treatment) history of cancer (Exceptions: basal cell carcinoma, intraepithelial cervical neoplasia).
- Patient has an active infectious disease (e.g., Hepatitis B, C).
- Patient had a myocardial infarction within the last 2 years.
- Patient has a current clinically important systemic illness that is likely to result in deterioration of the patient's condition or affect the subject's safety during the study:
- poorly controlled congestive heart failure (New York Heart Association [NYHA] score ≥ 3),
- poorly controlled diabetes,
- severe renal insufficiency (Estimated glomerular filtration rate < 30 mL/min),
- chronic liver disease - ALT (alanine aminotransferase) > 2x upper limit of normal range (ULN), AST (aspartate aminotransferase) > 2x ULN
- other clinically significant systemic illness, if considered relevant by the investigator.
- Patient had alcohol or drug dependence within the past year.
- Patient has a current diagnosis of epilepsy.
- Pregnant or breastfeeding women.
- Patient has participated in another interventional clinical trial within 12 weeks before Visit 01.
- Patient has contraindication for MRI imaging such as metallic endoprosthesis or MRI-incompatible stent implantation.
- Patient has contraindications for other study procedures, such as CSF sampling.
- Patient had surgery (under general anaesthesia) within 12 weeks prior to Visit 01 and/or scheduled surgery (under general anaesthesia) during the whole study period.
- Patient is currently being treated or was treated in the past with any active vaccines for a neurodegenerative disorder.
- Patients not expected to complete the clinical trial.
- Patient, in the opinion of the investigator, is unlikely to comply with the clinical study protocol, or is unsuitable for other reasons.
- Patient is dependent from Sponsor or investigator (e.g. as an employee or as a relative).
Trial locations and contacts
3 sites in 1 country.
Germany3 sites
Universitätsmedizin Göttingen, Klinik für Psychiatrie und Psychotherapie
Göttingen, 37075
Klinikum Rechts der Isar der TU München, Klinik und Poliklinik für Psychiatrie und Psychotherapie
München, 81675
Universitätsklinikum Ulm
Ulm, 89081
About this study
Official title: A 24-month Randomised Parallel Group Single-blinded Multi-centre Phase 1 Pilot Study of AADvac1 in Patients With Non Fluent Primary Progressive Aphasia
This study is a pilot trial evaluating the safety and immunogenicity of AADvac1 in patients with the non-fluent variant of Primary Progressive Aphasia.
50% of participants will receive the 40 µg dosage of AADvac1 and 50% of participants will receive the 160 µg dosage of AADvac1. No placebo is used.
Read the detailed description
The non-fluent variant of Primary progressive Aphasia (nfvPPA) is a chronic progressive neurodegenerative disorder of the brain. Over the course of the disease, pathological proteins accumulate in the brain, damaging neurons, thus causing them to lose their connections and die.
No treatments are currently available; symptomatic medications are used off-label in nfvPPA.
AADvac1 is designed to raise antibodies against pathological tau protein (the primary constituent of neurofibrillary pathology, which is the underlying cause of disease in ~80% of nfvPPA cases). These antibodies are expected to prevent tau protein from aggregating, to facilitate the removal of tau protein aggregates and prevent the spreading of pathology, slowing or halting the progress of the disease.
- Conditions
- Primary Progressive Nonfluent Aphasia
- Being tested
- AADvac1 40 µg, AADvac1 160 µg
- Keywords
- tau, neurofibrillary, degeneration, primary progressive aphasia, agrammatic, tauopathy, immunotherapy, immunization
- Medical subject headings
- Primary Progressive Nonfluent Aphasia, Pick Disease of the Brain, Aphasia, Primary Progressive, Tauopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AADvac1 40 µgDrug
Active immunotherapy against neurofibrillary pathology.
AADvac1 160 µgDrug
Active immunotherapy against neurofibrillary pathology.
| Study group | Role | What they receive |
|---|---|---|
| AADvac1 40 µg | Experimental | The intervention consists of Axon Peptide 108 coupled to keyhole limpet haemocyanin (KLH) 40 µg/0.30 mL suspension for injection; and aluminium hydroxide Al(OH)3 (containing approx. 0.5 mg Al3+/0.30 mL), administered subcutaneously. The basic immunisation regimen consists of 6 doses administered subcutaneously in 6-week intervals. Subsequently, 5 booster doses are applied in 13-week intervals, for a total of 11 administrations. Receives: Drug: AADvac1 40 µg |
| AADvac1 160 µg | Experimental | The intervention consists of Axon Peptide 108 coupled to KLH 160 µg/0.30 mL suspension for injection; and aluminium hydroxide Al(OH)3 (containing approx. 0.5 mg Al3+/0.30 mL), administered subcutaneously. The basic immunisation regimen consists of 6 doses administered subcutaneously in 6-week intervals. Subsequently, 5 booster doses are applied in 13-week intervals, for a total of 11 administrations. Receives: Drug: AADvac1 160 µg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
The safety assessment is based on the number, type and severity of adverse events (AEs).
Measured: 25 months
Immunogenicity (Percentage of patients who develop an IgG immune response, geometric mean titre of titre of antibodies against Axon Peptide 108, IgG to IgM ratio of antibodies against Axon Peptide 108)
AADvac1 depends on raising antibodies that mediate its treatment effects. Immunogenicity assessment includes: Percentage of AADvac1-treated patients who develop an immune response (responder rate), geometric mean titre of antibodies against Axon Peptide 108, IgG to IgM ratio of antibodies against Axon Peptide 108.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2017
- Study start31 Jul 2017
- Primary completionNov 2020 (estimated)
- Study completionNov 2020 (estimated)
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 Primary Progressive Nonfluent AphasiaStudies 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
- Model description
- Patients will be allocated to one of two dosage strengths of AADvac1. No placebo is used. No active comparator is used.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Axon Neuroscience SE
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Markus Otto, Prof, Principal investigator, Universitat Ulm
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03174886
- Sponsor's protocol ID
- AC-TP-001
- Other IDs
- 2017-000643-41, 2017
- Acronym
- AIDA
- Status last verified
- Nov 2019
- First submitted
- 29 May 2017
- Last updated
- 14 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Kontsekova E, Zilka N, Kovacech B, Skrabana R, Novak M. Identification of structural determinants on tau protein essential for its pathological function: novel therapeutic target for tau immunotherapy in Alzheimer's disease. Alzheimers Res Ther. 2014 Aug 1;6(4):45. doi: 10.1186/alzrt277. eCollection 2014.
PubMed 25478018Kontsekova 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 25478017Novak 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 27955995
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 24-month Randomised Parallel Group Single-blinded Multi-centre Phase 1 Pilot Study of AADvac1 in Patients With Non Fluent Primary Progressive Aphasia
- ClinicalTrials.gov ID
- NCT03174886
- Acronym / sponsor ID
- AIDA / AC-TP-001
- Conditions
- Primary Progressive Nonfluent Aphasia
- Keywords
- tau, neurofibrillary, degeneration, primary progressive aphasia, agrammatic, tauopathy, immunotherapy, immunization
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Axon Neuroscience SEIndustry (pharma, biotech, devices)
- Study start
- 31 Jul 2017 (actual)
- Primary completion
- Nov 2020 (estimated)
- Study completion
- Nov 2020 (estimated)
- First posted
- 5 Jun 2017 (actual)
- 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 study is a pilot trial evaluating the safety and immunogenicity of AADvac1 in patients with the non-fluent variant of Primary Progressive Aphasia.
50% of participants will receive the 40 µg dosage of AADvac1 and 50% of participants will receive the 160 µg dosage of AADvac1. No placebo is used.
Detailed description
The non-fluent variant of Primary progressive Aphasia (nfvPPA) is a chronic progressive neurodegenerative disorder of the brain. Over the course of the disease, pathological proteins accumulate in the brain, damaging neurons, thus causing them to lose their connections and die.
No treatments are currently available; symptomatic medications are used off-label in nfvPPA.
AADvac1 is designed to raise antibodies against pathological tau protein (the primary constituent of neurofibrillary pathology, which is the underlying cause of disease in ~80% of nfvPPA cases). These antibodies are expected to prevent tau protein from aggregating, to facilitate the removal of tau protein aggregates and prevent the spreading of pathology, slowing or halting the progress of the disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Patients will be allocated to one of two dosage strengths of AADvac1. No placebo is used. No active comparator is used.
| Arm | Type | Receives |
|---|---|---|
| AADvac1 40 µg | Experimental | Drug: AADvac1 40 µgThe intervention consists of Axon Peptide 108 coupled to keyhole limpet haemocyanin (KLH) 40 µg/0.30 mL suspension for injection; and aluminium hydroxide Al(OH)3 (containing approx. 0.5 mg Al3+/0.30 mL), administered subcutaneously. The basic immunisation regimen consists of 6 doses administered subcutaneously in 6-week intervals. Subsequently, 5 booster doses are applied in 13-week intervals, for a total of 11 administrations. |
| AADvac1 160 µg | Experimental | Drug: AADvac1 160 µgThe intervention consists of Axon Peptide 108 coupled to KLH 160 µg/0.30 mL suspension for injection; and aluminium hydroxide Al(OH)3 (containing approx. 0.5 mg Al3+/0.30 mL), administered subcutaneously. The basic immunisation regimen consists of 6 doses administered subcutaneously in 6-week intervals. Subsequently, 5 booster doses are applied in 13-week intervals, for a total of 11 administrations. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patient has a clinical diagnosis of non-fluent/agrammatic variant PPA according to the criteria by Gorno-Tempini et al. (2011) with evidence of left frontal brain hypometabolism. Patients with right-sided hypometabolism are eligible for the study only if they are left-handed.
- Patient has a FTLD-CDR language domain score of ≤ 2, and other individual FTLD-CDR domain scores ≤ 1.
- Patient's age is 18 - 85 years inclusive at the time of having provided informed consent.
- Patient has adequate visual and auditory abilities and premorbid local language skills to allow neuropsychological testing.
- Sexually active female patients must be using highly effective contraception methods, or be surgically sterile, or be at least 2 years post-menopausal.
Key exclusion criteria (32 listed)
- The patient's brain MRI is incompatible with a diagnosis of nfvPPA.
- Patient has a history or evidence of a central nervous system (CNS) disorder other than nfvPPA which may cause symptoms of aphasia or dementia (Alzheimer's disease, Dementia with Lewy Bodies, inflammatory/demyelinating CNS conditions, Creutzfeldt-Jakob disease, Huntington's disease, etc.)
- Patient has a history or currently suffers from a significant psychiatric illness such as schizophrenia, any type of psychotic disorder or bipolar affective disorder.
- Patient has a history or evidence of cerebrovascular disease (ischemic or haemorrhagic stroke), or diagnosis of possible, probable or definite vascular dementia.
- Patient has Wernicke's encephalopathy.
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 |
|---|---|---|
| AADvac1 40 µgActive immunotherapy against neurofibrillary pathology. | Drug | AADvac1 40 µg |
| AADvac1 160 µgActive immunotherapy against neurofibrillary pathology. | Drug | AADvac1 160 µg |
Primary outcome
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: 25 months
The safety assessment is based on the number, type and severity of adverse events (AEs).
Immunogenicity (Percentage of patients who develop an IgG immune response, geometric mean titre of titre of antibodies against Axon Peptide 108, IgG to IgM ratio of antibodies against Axon Peptide 108)
Time frame: 24 months
AADvac1 depends on raising antibodies that mediate its treatment effects. Immunogenicity assessment includes: Percentage of AADvac1-treated patients who develop an immune response (responder rate), geometric mean titre of antibodies against Axon Peptide 108, IgG to IgM ratio of antibodies against Axon Peptide 108.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2019.
- Background: PubMed 25478018Kontsekova E, Zilka N, Kovacech B, Skrabana R, Novak M. Identification of structural determinants on tau protein essential for its pathological function: novel therapeutic target for tau immunotherapy in Alzheimer's disease. Alzheimers Res Ther. 2014 Aug 1;6(4):45. doi: 10.1186/alzrt277. eCollection 2014.
- Background: 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.
- Background: 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.
- Individual participant dataSharing planned: Undecided
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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.
Markus Otto, Prof principal investigator
Universitat Ulm
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 40 µg and AADvac1 160 µg in people with Primary Progressive Nonfluent Aphasia, run by Axon Neuroscience SE at 3 sites in Germany.
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 9 inclusion and 32 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: status not confirmed, as of the sponsor's last update on 14 Nov 2019. 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 Germany. 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. 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?
Results are not available in the source record.
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?
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (time frame: 25 months). The study lists 2 primary outcomes in all. 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 NCT03174886, 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 14 Nov 2019.