A 24-month Phase 1 Pilot Study of AADvac1 in Patients With Non Fluent Primary Progressive Aphasia

NCT03174886 | Unknown Phase 1 DMC

• 2 other identifiers: AC-TP-0012017-000643-41
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Primary Progressive Nonfluent Aphasia

Keywords

tau; neurofibrillary; degeneration; primary progressive aphasia; agrammatic; tauopathy; immunotherapy; immunization

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  The safety assessment is based on the number, type and severity of adverse events (AEs).

  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.

  24 months

Other Outcomes (12)

• Cerebrospinal fluid (CSF) biomarkers

  24 months

• Serum neurofilament light chain protein (and other blood biomarkers of nfvPPA)

  24 months

• Magnetic resonance imaging (MRI) volumetry

  24 months

Study Arms (2)

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.

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.

Drug: AADvac1 160 µg

Interventions

AADvac1 40 µg DRUG

Active immunotherapy against neurofibrillary pathology.

AADvac1 40 µg

AADvac1 160 µg DRUG

Active immunotherapy against neurofibrillary pathology.

AADvac1 160 µg

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Axon Neuroscience SE: lead

Study Sites (3)

Universitätsmedizin Göttingen, Klinik für Psychiatrie und Psychotherapie

Göttingen, 37075, Germany

Location

Klinikum Rechts der Isar der TU München, Klinik und Poliklinik für Psychiatrie und Psychotherapie

München, 81675, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Related Publications (3)

• 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.

  PMID: 25478018 BACKGROUND

• Kontsekova 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.

  PMID: 25478017 BACKGROUND

• 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.

  PMID: 27955995 BACKGROUND

MeSH Terms

Conditions

Primary Progressive Nonfluent Aphasia; Pick Disease of the Brain; Aphasia, Primary Progressive; Tauopathies

Interventions

AADvac1

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Neurodegenerative Diseases; Aphasia; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Frontotemporal Dementia

Study Officials

• Markus Otto, Prof

  Universitat Ulm

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Patients are unaware of the dosage strength they are receiving. The AADvac1 vials are numbered, and the coding unknown to the patient. The investigator handles the vaccine vials and administers the IMP.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will be allocated to one of two dosage strengths of AADvac1. No placebo is used. No active comparator is used.

Study Record Dates

• First Submitted: May 29, 2017
• First Posted: June 5, 2017
• Study Start: July 31, 2017
• Primary Completion: November 1, 2020
• Study Completion: November 1, 2020
• Last Updated: November 14, 2019

Record last verified: 2019-11

Locations

DE (3)