Mild Cognitive ImpairmentPhase 2NCT03461276
Safety and Immunogenicity of Repeated Doses of ABvac40 in Patients With a-MCI or Vm-AD
A Phase 2 study testing ABvac40 in people with Mild Cognitive Impairment and Alzheimer Disease, run by Araclon Biotech S.L. at 23 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 55 to 80 years
- Conditions the study is for
- Mild Cognitive Impairment, Alzheimer Disease
- What is being tested?
- ABvac40
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 134 participants
- Where
- 23 sitesin 4 countries
- Study dates
- 13 Dec 2017to 23 Mar 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 55 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A subject must meet all the following inclusion criteria:
- 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.
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- 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.
Who cannot join
- A subject meeting any of the following exclusion criteria is NOT eligible for participation in the study.
- 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.
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- 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.
- Patients being treated with anticoagulants or antiaggregant therapy (aspirin at a prophylactic dose ≤ 325 mg daily or clopidogrel at a dose ≤75 mg daily are allowed) should not be recruited in the study.
- Modified Hachinski Ischemic Scale, score higher than 4.
- Surgery (with general anaesthetic) within the previous three months to be included in the trial or programed during the study period.
- Treatment within 30 days prior to visit 0 with systemic corticosteroids or other immunosuppressant's.
- Vaccination against influenza or any other vaccination within 2 months before first IMP dose.
- Patients, who have previously been randomized in this trial.
- Participation in another clinical trial within the previous 1 month to screening visit, or within the previous 12 months after the last dose to the screening visit in the case of subjects who participated in trials with a study drug whose intention was to modify the progression AD unless documentation of receipt of placebo is available. The patient cannot be included in the study if the experimental drug was an immunotherapeutic drug, including IVIG or a vaccine against Alzheimer's disease unless documentation of receipt of placebo is available.
- Patients with alcohol or drug abuse or dependence.
- Absolute (having a pacemaker or implantable defibrillator) or relative (bare metal stent or stent implanted in the last six months) contraindications to MRI examination. Feeling of claustrophobic do not let perform MRI or PET scan.
- Patients unlikely to comply with the protocol (e.g., unable to return for follow-up visits).
- Women of childbearing potential, pregnant or nursing.
- Significant alterations in the EKG that are associated with an added risk for the patient.
Trial locations and contacts
23 sites in 4 countries.
23 sites in 4 countries
Spain18 sites
Cae Oroitu
Algorta, Vizcaya, 48993
Hospital General Universitario de Alicante
Alicante, Alicante, 03010
Barcelona Beta Brain Research Center (BBRC)
Barcelona, Barcelona, 08005
Hospital de la Santa Creu i Sant Pau
Barcelona, Barcelona, 08025
Fundació ACE
Barcelona, Barcelona, 08028
Hospital Vall d'Hebron
Barcelona, Barcelona, 08035
Hospital del Mar
Barcelona, Barcelona
Hospital U. de Burgos
Burgos, Burgos, 09006
Hospital Ramón y Cajal
Colmenar Viejo, Madrid, 28034
Hospital Universitario Donosti
Donostia / San Sebastian, Guipuzcoa, 20014
Hospital Santa Maria de Lleida
Lleida, Lleida, 25198
Hospital San Pedro
Logroño, La Rioja, 26006
Complejo Hospitalario Ruber Juan Bravo
Madrid, Madrid, 28006
Hospital Universitario 12 Octubre
Madrid, Madrid, 28010
Hospital Clínico San Carlos
Madrid, Madrid, 28040
CUN - Clínica Universidad de Navarra
Pamplona, Navarre, 31008
Hospital Mútua de Terrasa
Terrassa, Barcelona, 08221
Hospital Clínico Universitario Lozano Blesa
Zaragoza, Zaragoza, 50009
France3 sites
Hôpital François Mitterrand
Dijon, Bourgogne-Franche-Comté, 21000
CHU de Montpellier
Montpellier, 34295
Centre de Recherche Clinique du Gérontopôle
Toulouse, 31059
About this study
Official title: A Multi-center, Randomized, Double-blind, Placebo-controlled, 24 Months Study in Patients With Amnestic Mild Cognitive Impairment or Very Mild Alzheimer's Disease to Investigate the Safety, Tolerability and Immune Response of Repeated Subcutaneous Injections of ABvac40
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.
Read more
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
- Being tested
- ABvac40, Placebo
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABvac40Biological
ABvac40 consists in a conjugate of Aβx-40 with a carrier protein (KLH) vehiculated in phosphate buffer containing 0.35% aluminum hydroxide as adjuvant.
PlaceboBiological
Placebo consists in the vaccine's vehicle (phosphate buffer containing 0.35% aluminum hydroxide) without the conjugate.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Number of withdrawn subjects due to treatment-emergent adverse events (TEAEs) during the whole study.
Measured: 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
Clinically significant (CS) abnormalities in physical examination reported during the study.
Measured: 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
Clinically significant (CS) abnormalities in neurological examination reported during the study.
Measured: 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
Clinically significant (CS) abnormalities in hematology parameters reported during the study.
Measured: 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
Clinically significant (CS) abnormalities in biochemistry parameters reported during the study.
Measured: 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 Coagulation
Clinically significant (CS) abnormalities in coagulation parameters reported during the study.
Measured: Entire study duration (Week 0 to Week 104 in Part A, and Week 0 to Week 77 in Part B)
Level of Anti-Aβ40 Antibodies in CSF
The change in levels of anti-Aβ40 antibodies in cerebrospinal fluid (CSF) from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included the recorded outcome value as the dependent variable; treatment, protocol specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 50A and Week 104A)
Level of Anti-Aβ40 Antibodies in Plasma
The change in levels of anti-Aβ40 antibodies in plasma from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included the recorded outcome value as the dependent variable; treatment, protocol specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline age as covariates; and measures within-patient at each visit as a repeated measure. A compound symmetric variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)
Level of Antibody-secreting Cells
The change in levels of antibody-secreting cells from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included the recorded outcome value as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)
Level of Aβ40 Peptides in Plasma - ABtest-IA
The change in levels of anti-Aβ40 peptides in plasma (ABtest-IA) from baseline to each applicable postbaseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)
Level of Aβ42 Peptides in Plasma - ABtest-IA
The change in levels of anti-Aβ42 peptides in plasma (ABtest-IA) from baseline to each applicable postbaseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)
Level of Aβ40 Peptides in Plasma - ABtest-MS
The change in levels of anti-Aβ40 peptides in plasma (ABtest-MS) from baseline to each applicable postbaseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. A compound symmetric variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)
Level of Aβ42 Peptides in Plasma - ABtest-MS
The change in levels of anti-Aβ42 peptides in plasma (ABtest-MS) from baseline to each applicable postbaseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)
Cortical Fibrillary Amyloid Deposition Assessed by a-PET Scans
The change in amyloid-PET (a-PET) standard centiloid global cortical area (reference Pons) from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 50A and Week 104A)
Percentage of Change in Brain Volume
The percent change in brain volume from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 24A, Week 50A, and Week 104A)
Percentage of Change in Hippocampal Volume
The percent change in right and left hippocampal volume from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 24A, Week 50A, Week 104A)
Percentage of Change in Ventricular Volume
The percent change in ventricular volume from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 24A, Week 50A, and Week 104A)
Level of Aβ42 Peptides in CSF
The change in levels of Aβ42 peptides in cerebrospinal fluid (CSF) from baseline to each applicable postbaseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 50A and Week 104A)
Level of Aβ40 Peptides in CSF
The change in levels of Aβ40 peptides in cerebrospinal fluid (CSF) from baseline to each applicable postbaseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 50A and Week 104A)
Aβ42/Aβ40 Ratio in CSF
The change in Aβ42/Aβ40 ratio in cerebrospinal fluid (CSF) from baseline to each applicable postbaseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 50A and Week 104A)
Level of Total Tau in CSF
The change in levels of total Tau in cerebrospinal fluid (CSF) from baseline to each applicable postbaseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 50A and Week 104A)
Level of p-Tau 181 in CSF
The change in levels of p-Tau 181 in cerebrospinal fluid (CSF) from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 50A and Week 104A)
Level of Neurofilament Light in CSF
The change in levels of neurofilament light in cerebrospinal fluid (CSF) from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 50A and Week 104A)
Level of Neurogranin in CSF
The change in levels of neurogranin in cerebrospinal fluid (CSF) from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 50A and Week 104A)
Mini Mental State Examination (MMSE) Score
The change in MMSE score from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a MMRM and the ITT analysis set.
MMSE is an 11-question measure that tests 5 areas of cognitive function: orientation, registration, attention and calculation, recall, and language. MMSE score ranges: 0-30, with lower scores indicating worst cognition.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (baseline, and post-baseline at Week 24A, Week 50A, Week 77A, and Week 104A)
Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score
The change in CDR-SB score from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a MMRM and the ITT analysis set.
CDR-SB assesses 6 cognitive and functional domains: Memory, Orientation, Judgment \& Problem Solving, Community Affairs, Home \& Hobbies, Personal Care. CDR-SB score ranges: 0-18. The higher scores mean a worst outcome.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 24A, Week 50A, Week 77A, and Week 104A)
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score
The change in RBANS total score from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a MMRM and the ITT analysis set.
RBANS assesses 5 cognitive domains: Immediate Memory, Visuospatial/constructional, Language, Attention, Delayed Memory. Total score (range 40-160) sums the 5 domain scores. The higher scores mean a better outcome.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 24A, Week 50A, Week 77A, and Week 104A)
Alzheimer's Disease Cooperative Study - Activities of Daily Living, Mild Cognitive Impairment (ADCS-ADL MCI) Score
The change in ADCS-ADL MCI total score from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a MMRM and the ITT analysis set.
ADCS-ADL MCI is a 24-item scale that includes 6 basic activities of daily living (ADL) items and 16 instrumental ADL items that provide a total score: 0-78, with a lower score indicating greater severity.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 24A, Week 50A, Week 77A, and Week 104A)
Trail Making Test (TMT) Scores
Change in TMT score from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a MMRM and the ITT analysis set.
TMT has 2 parts in which the patient connects 25 dots in order as quickly as possible. In TMT-A, targets are numbers 1-25; in TMT-B, targets are numbers 1-13 interleaved with letters A-L. Lower timings indicate better outcome.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 24A, Week 50A, Week 77A, and Week 104A)
Investigator Global Evaluation (IGE) Score
Change in IGE from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using MMRM and ITT analysis set.
IGE at baseline:1-Good general status;2-Slight deterioration;3-Moderate deterioration;4-Bad general status.
IGE after baseline:1-Marked improvement;2-Moderate improvement;3-Slight improvement;4-No change;5-Slight worsening;6-Moderate worsening;7-Marked worsening.
MMRM included IGE after baseline as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix is used. Following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly significantly associated with response measure (p < 0.15).
Measured: Part A (Week 24A, Week 50A, and Week 104A)
Columbia Suicide Severity Rating Scale
Subjects with suicidal ideation or suicidal behavior since last visit.
Measured: Part A (Week 24A, Week 50A, Week 77A, and Week 104A)
EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Overall Severity Index Score
Change in EQ-5D-5L overall severity index from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using MMRM and ITT analysis set.
EQ-5D-5L has 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression; rated: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 50A and Week 104A)
EuroQol 5 Dimensions 5 Levels - Visual Analogue Scale (EQ-5D-5L - VAS) Score
The change in EQ-5D-5L - VAS score from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.
VAS records the patient's self-rated health on a vertical scale, ranging from 100 = 'Best imaginable health state' down to 0 = 'Worst imaginable health state'.
The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have been included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).
Measured: Part A (Week 50A and Week 104A)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2018
- Study start13 Dec 2017
- Primary completion23 Mar 2023
- Study completion23 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- Araclon Biotech S.L.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03461276
- Sponsor's protocol ID
- AB1601
- Status last verified
- Apr 2026
- First submitted
- 2 Mar 2018
- Last updated
- 5 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41058018Pascual-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. Long-term safety and immunogenicity of ABvac40 active immunotherapy in mild cognitive impairment and very mild Alzheimer's disease: Results from AB1601 phase 2 extension study. Alzheimers Dement. 2026 Aug;22(8):e71746. doi: 10.1002/alz.71746.
PubMed 42590850
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Randomized, Double-blind, Placebo-controlled, 24 Months Study in Patients With Amnestic Mild Cognitive Impairment or Very Mild Alzheimer's Disease to Investigate the Safety, Tolerability and Immune Response of Repeated Subcutaneous Injections of ABvac40
- ClinicalTrials.gov ID
- NCT03461276
- Acronym / sponsor ID
- AB1601
- Conditions
- Mild Cognitive Impairment, Alzheimer Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 134 participants (actual)
- Lead sponsor
- Araclon Biotech S.L.Industry (pharma, biotech, devices)
- Study start
- 13 Dec 2017 (actual)
- Primary completion
- 23 Mar 2023 (actual)
- Study completion
- 23 Mar 2023 (actual)
- First posted
- 12 Mar 2018 (actual)
- Results
- Posted 3 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ABvac40 | Experimental | Biological: ABvac40Six 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. |
| Placebo | Placebo comparator | Biological: PlaceboSix 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. |
Who may qualify
- Ages
- 55 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (28 listed)
- A subject meeting any of the following exclusion criteria is NOT eligible for participation in the study.
- 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).
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 |
|---|---|---|
| ABvac40ABvac40 consists in a conjugate of Aβx-40 with a carrier protein (KLH) vehiculated in phosphate buffer containing 0.35% aluminum hydroxide as adjuvant. | Biological | ABvac40 |
| PlaceboPlacebo consists in the vaccine's vehicle (phosphate buffer containing 0.35% aluminum hydroxide) without the conjugate. | Biological | Placebo |
Primary outcome
Average Maximal Increment of Anti-Aβ40 Antibody Signal (Optical Density [OD] in ELISA)
Time frame: 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)
Average maximal increment (MΔ) of plasma anti-Aβ40 antibody signal (optical density [OD] in ELISA) in each subject with regard to Baseline visit.
33 secondary outcomes
Subject Discontinuations Due to TEAEs
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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 Coagulation
Time frame: Entire study duration (Week 0 to Week 104 in Part A, and Week 0 to Week 77 in Part B)
Level of Anti-Aβ40 Antibodies in CSF
Time frame: Part A (Week 50A and Week 104A)
Level of Anti-Aβ40 Antibodies in Plasma
Time frame: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)
Level of Antibody-secreting Cells
Time frame: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)
Level of Aβ40 Peptides in Plasma - ABtest-IA
Time frame: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)
Level of Aβ42 Peptides in Plasma - ABtest-IA
Time frame: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)
Level of Aβ40 Peptides in Plasma - ABtest-MS
Time frame: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)
Level of Aβ42 Peptides in Plasma - ABtest-MS
Time frame: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)
Cortical Fibrillary Amyloid Deposition Assessed by a-PET Scans
Time frame: Part A (Week 50A and Week 104A)
Percentage of Change in Brain Volume
Time frame: Part A (Week 24A, Week 50A, and Week 104A)
Percentage of Change in Hippocampal Volume
Time frame: Part A (Week 24A, Week 50A, Week 104A)
Percentage of Change in Ventricular Volume
Time frame: Part A (Week 24A, Week 50A, and Week 104A)
Level of Aβ42 Peptides in CSF
Time frame: Part A (Week 50A and Week 104A)
Level of Aβ40 Peptides in CSF
Time frame: Part A (Week 50A and Week 104A)
Aβ42/Aβ40 Ratio in CSF
Time frame: Part A (Week 50A and Week 104A)
Level of Total Tau in CSF
Time frame: Part A (Week 50A and Week 104A)
Level of p-Tau 181 in CSF
Time frame: Part A (Week 50A and Week 104A)
Level of Neurofilament Light in CSF
Time frame: Part A (Week 50A and Week 104A)
Level of Neurogranin in CSF
Time frame: Part A (Week 50A and Week 104A)
Mini Mental State Examination (MMSE) Score
Time frame: Part A (baseline, and post-baseline at Week 24A, Week 50A, Week 77A, and Week 104A)
Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score
Time frame: Part A (Week 24A, Week 50A, Week 77A, and Week 104A)
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score
Time frame: Part A (Week 24A, Week 50A, Week 77A, and Week 104A)
Alzheimer's Disease Cooperative Study - Activities of Daily Living, Mild Cognitive Impairment (ADCS-ADL MCI) Score
Time frame: Part A (Week 24A, Week 50A, Week 77A, and Week 104A)
Trail Making Test (TMT) Scores
Time frame: Part A (Week 24A, Week 50A, Week 77A, and Week 104A)
Investigator Global Evaluation (IGE) Score
Time frame: Part A (Week 24A, Week 50A, and Week 104A)
Columbia Suicide Severity Rating Scale
Time frame: Part A (Week 24A, Week 50A, Week 77A, and Week 104A)
EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Overall Severity Index Score
Time frame: Part A (Week 50A and Week 104A)
EuroQol 5 Dimensions 5 Levels - Visual Analogue Scale (EQ-5D-5L - VAS) Score
Time frame: Part A (Week 50A and Week 104A)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 41058018Pascual-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.
- Derived from this study: PubMed 42590850Pascual-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. Long-term safety and immunogenicity of ABvac40 active immunotherapy in mild cognitive impairment and very mild Alzheimer's disease: Results from AB1601 phase 2 extension study. Alzheimers Dement. 2026 Aug;22(8):e71746. doi: 10.1002/alz.71746.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
23 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ABvac40 in people with Mild Cognitive Impairment and Alzheimer Disease, run by Araclon Biotech S.L. at 23 sites in 4 countries.
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 11 inclusion and 28 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 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Spain, France, Italy, Sweden. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Average Maximal Increment of Anti-Aβ40 Antibody Signal (Optical Density [OD] in ELISA) (time frame: 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)). 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 NCT03461276, which also lists 2 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 5 May 2026.