Safety and Immunogenicity of Repeated Doses of ABvac40 in Patients With a-MCI or Vm-AD

NCT03461276 | Completed Phase 2 Results DMC

• 1 other identifier: AB1601
• Study Type: interventional
• Target: 134
• Locations: 4 countries
• Sites: 23

Brief Summary

Alzheimer's disease (AD) is the most common type of dementia, accounting for 50-75% of the estimated 47 million people with dementia worldwide. The amyloid cascade hypothesis of AD proposes that amyloid-β (Aβ) peptide accumulation in the brain, caused by an imbalance between Aβ production and clearance, is the initiating factor of a cascade ultimately leading to dementia. Aβ peptides are generated from sequential cleavage of the amyloid precursor protein (APP), including Aβ40 and Aβ42. Aβ40 is the predominant variant (90%) among the secreted Aβ forms and although Aβ42 is more hydrophobic and prone to aggregate, and Aβ42 oligomers are regarded to be the most neurotoxic species, Aβ40 can also produce highly toxic diffusible aggregates, which can be prevented in vitro by specific anti-Aβ40 antibodies. Several studies have proposed that a high concentration of Aβ40 in the brain distinguishes patients with AD from those who have senile plaques but are cognitively normal, pointing to the importance of Aβ40 in the onset of dementia. In keeping with this, previous studies have demonstrated that specific anti-Aβ40 antibodies label NFTs in the entorhinal cortex and the hippocampus of AD brains, and that these do not co-localize with tau NFTs, suggesting the presence of degenerating neuronal populations filled with C-terminal fragments of Aβx-40. In addition, Aβ40 is the main component of amyloid deposition around cerebral arteries causing cerebral amyloid angiopathy (CAA), which has a prevalence of about 80-90% in patients with AD (for more information see Lacosta et al. Alzheimer's Research \& Therapy (2018) 10:12 DOI 10.1186/s13195-018-0340-8). Considering those previous results suggesting that strategies targeting Aβ40 could represent novel disease-modifying therapies, we have developed ABvac40, the first active vaccine targeting the C-terminal end of the Aβ40 peptide. The purpose of this Phase II study is to confirm in patients with a-MCI or vm-AD the level of safety and tolerability obtained in the ABvac40 Phase I clinical trial in patients with mm-AD. In addition, the study is aimed to better characterize the immune response elicited by ABvac40 and to explore its effects on AD biomarkers.

Conditions

Mild Cognitive Impairment; Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• Average Maximal Increment of Anti-Aβ40 Antibody Signal (Optical Density [OD] in ELISA)

  Average maximal increment (MΔ) of plasma anti-Aβ40 antibody signal (optical density \[OD\] in ELISA) in each subject with regard to Baseline visit.

  Part A (Baseline, and post-Baseline visits at Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)

Secondary Outcomes (33)

• Subject Discontinuations Due to TEAEs

  Entire study duration (Week 0 to Week 104 in Part A, and Week 0 to Week 77 in Part B)

• Number of Subjects With Clinically Significant Abnormalities in Physical Examination

  Entire study duration (Week 0 to Week 104 in Part A, and Week 0 to Week 77 in Part B)

• Number of Subjects With Clinically Significant Abnormalities in Neurological Examination

  Entire study duration (Week 0 to Week 104 in Part A, and Week 0 to Week 77 in Part B)

• Number of Subjects With Clinically Significant Abnormalities in Analytical Hematology

  Entire study duration (Week 0 to Week 104 in Part A, and Week 0 to Week 77 in Part B)

• Number of Subjects With Clinically Significant Abnormalities in Analytical Biochemistry

  Entire study duration (Week 0 to Week 104 in Part A, and Week 0 to Week 77 in Part B)

Other Outcomes (1)

• Average Maximal Increment of Anti-Aβ40 Antibody Signal (Optical Density [OD] in ELISA) - Sensitivity

  Part A (Baseline, and post-Baseline visits at Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)

Study Arms (2)

ABvac40

EXPERIMENTAL

Six administrations of ABvac40; the first five administered once every 4 weeks and the sixth at week 42. Each administration consists of 1mL subcutaneous injection of ABvac40.

Biological: ABvac40

Placebo

PLACEBO COMPARATOR

Six administrations of Placebo; the first five administered once every 4 weeks and the sixth at week 42. Each administration consists of 1mL subcutaneous injection of the vaccine's vehicle buffer without the active component.

Biological: Placebo

Interventions

ABvac40 BIOLOGICAL

ABvac40 consists in a conjugate of Aβx-40 with a carrier protein (KLH) vehiculated in phosphate buffer containing 0.35% aluminum hydroxide as adjuvant.

ABvac40

Placebo BIOLOGICAL

Placebo consists in the vaccine's vehicle (phosphate buffer containing 0.35% aluminum hydroxide) without the conjugate.

Placebo

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between 55 and 80 years of age, both inclusive, at the time of signing informed consent.
• The patient (or legal representative, if applicable) and a close relative/caregiver must read the subject information sheet, agree to participate in the clinical trial and sign the informed consent form (the patient and a close relative/caregiver).
• Presence of a stable caregiver to attend the patient study visits.
• Mini-Mental Status Examination (MMSE) score between 24 and 30 points (inclusive), according to age and education level.
• Clinical Dementia Rating (CDR) scale scoring 0.5.
• Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score on the Delayed Memory Index (DMI) of 85 or lower.
• The results of the patient's MRI brain scan must be concordant with the diagnosis of clinical a-MCI or vm-AD according to the following criteria: Scheltens scale, and measurement of white matter and past haemorrhages.
• If the patient is receiving treatment for AD, must have been stable during the two months before the selection visit.
• Treatment for concomitant diseases must be stable during the previous month before the treatment of the study.
• Positive assessment of the candidate by the investigator for complying with the requirements and procedures of the study.

You may not qualify if:

• Known allergy to components of the vaccine or prior history of anaphylaxis, a severe allergic reaction or a history of hypersensitivity to any component of the formulation. Allergy to fish or shellfish.
• Active infectious disease (i.e. hepatitis B, C). Positive syphilis serology.
• History or presence of autoimmune disease, except mild eczema, rhinitis or psoriasis.
• Presence or history of immunodeficiency (i.e. HIV).
• Significant kidney and/or liver disease.
• History of asthma or reactive airway disease with bronchospasm in the last 6 months, or currently on regular treatment.
• Major uncontrolled systemic condition (e.g. diabetes, congestive heart failure, hypertension).
• History of cancer (≤5 years since the last specific treatment). Exceptions: basocellular carcinoma.
• Significant alterations in hematological, biochemical or urine analytical parameters, particularly those relating to levels of vitamin B12, folic acid or thyroid tests.
• History of any other central nervous system disorder, degenerative or non-degenerative neurological or psychiatric condition that, in the investigator's opinion could be the cause of the dementia, or could explain the cognitive impairment, or that might interfere with cognitive function directly or by its treatment.
• Geriatric Depression Scale (GDS; abbreviated version), score \>5
• Has a "yes" answer to C-SSRS suicidal ideation items 4 or 5, or any suicidal behavior within 6 months before Screening, or has been hospitalized or treated for suicidal behavior in the past 5 years before Screening.
• History or signs of cerebrovascular disease (ischemic or haemorrhagic stroke, transient ischemic attack), or diagnosis of possible, probable or clear vascular dementia according to NINDS-AIREN criteria.
• Presence on MRI of a relevant pattern of microvascular disease (Leukoaraiosis, Fazekas score ≥2 in the deep white matter scale or ≥4 in the global score) or more than one lacunar or territorial infarcts. Any other MRI finding that, in the opinion of the investigator, might be a relevant contributing cause of subject´s cognitive impairment. Presence of up to 3 microhemorrhages will be acceptable.
• History of bleeding disorder or predisposing conditions, blood clotting or clinically significant abnormal results on coagulation profile at Screening, as determined by the Investigator.

Sponsors & Collaborators

• Araclon Biotech S.L.: lead

Study Sites (23)

Hôpital François Mitterrand

Dijon, Bourgogne-Franche-Comté, 21000, France

Location

CHU de Montpellier

Montpellier, 34295, France

Location

Centre de Recherche Clinique du Gérontopôle

Toulouse, 31059, France

Location

San Giovanni di Dio - Fatebenefratelli

Brescia, 25125, Italy

Location

Hospital General Universitario de Alicante

Alicante, Alicante, 03010, Spain

Location

Barcelona Beta Brain Research Center (BBRC)

Barcelona, Barcelona, 08005, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Barcelona, 08025, Spain

Location

Fundació ACE

Barcelona, Barcelona, 08028, Spain

Location

Hospital Vall d'Hebron

Barcelona, Barcelona, 08035, Spain

Location

Hospital del Mar

Barcelona, Barcelona, Spain

Location

Hospital Mútua de Terrasa

Terrassa, Barcelona, 08221, Spain

Location

Hospital U. de Burgos

Burgos, Burgos, 09006, Spain

Location

Hospital Universitario Donosti

Donostia / San Sebastian, Guipuzcoa, 20014, Spain

Location

Hospital San Pedro

Logroño, La Rioja, 26006, Spain

Location

Hospital Santa Maria de Lleida

Lleida, Lleida, 25198, Spain

Location

Hospital Ramón y Cajal

Colmenar Viejo, Madrid, 28034, Spain

Location

Complejo Hospitalario Ruber Juan Bravo

Madrid, Madrid, 28006, Spain

Location

Hospital Universitario 12 Octubre

Madrid, Madrid, 28010, Spain

Location

Hospital Clínico San Carlos

Madrid, Madrid, 28040, Spain

Location

CUN - Clínica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Cae Oroitu

Algorta, Vizcaya, 48993, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Zaragoza, 50009, Spain

Location

Karolinska Universitetssjukhuset

Stockholm, 141 86, Sweden

Location

Related Publications (1)

• Pascual-Lucas M, Lacosta AM, Montanes M, Canudas J, Loscos J, Monleon I, Allue JA, Sarasa L, Fandos N, Romero J, Sarasa M, Torres M, Whyms D, Terencio J, Pinol-Ripoll G, Boada M. Safety, tolerability, immunogenicity, and efficacy of ABvac40 active immunotherapy against Abeta40 in patients with mild cognitive impairment or very mild Alzheimer's disease: A randomized, double-blind, placebo-controlled phase 2 study. Alzheimers Dement. 2025 Oct;21(10):e70776. doi: 10.1002/alz.70776.

  PMID: 41058018 RESULT

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: Maria Pascual Lucas
• Organization: Araclon Biotech, S.L.

mpascual@araclon.com

+34976796562

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2018
• First Posted: March 12, 2018
• Study Start: December 13, 2017
• Primary Completion: March 23, 2023
• Study Completion: March 23, 2023
• Last Updated: May 5, 2026
• Results First Posted: February 3, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); IT (1); FR (3); ES (18)