Repeated Subcutaneous Administration of ABvac40 in Mild to Moderate Alzheimer's Disease Patients
Primary Purpose
Alzheimer's Disease
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
ABvac40
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer's Disease
Eligibility Criteria
Inclusion Criteria:
- Clinical diagnosis suggesting Alzheimer's disease (AD) based on the criteria of the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA).
- The results of the patient's MRI brain scan had to be concordant with the diagnosis of AD according to the following criteria: Scheltens scale, and quantitative measurement of white matter and past hemorrhages.
- Severity of Alzheimer's disease (AD) assessed as mild or moderate using the Mini Mental State Examination (MMSE) scale. Mild or moderate AD was confirmed if the MMSE score varied between 15 and 26.
- The Hachinski ischemic scale was used to distinguish AD from multi-infarct dementia. A score of ≤4 suggested AD.
- Score on the Clinical Dementia Rating Scale (CDR) of 0.5 or 1.0.
- Be receiving a stable dose of treatment for AD for three months before the selection visit, and expecting to continue treatment for the duration of the study (if appropriate).
- Stable treatment for other illnesses may be administered 30 days prior to V0 (selection).
- Males or females from 50 to 85 years of age, inclusive (at the time of signing informed consent).
- The patient (or a close relative or legal representative) should read the patient information sheet, agreed to participate in the clinical trial and signed Inform consent (IC) (the patient and a close relative or legal representative).
- Presence of a stable caregiver willing to attend patient visits during the study.
- Sufficient visual and auditory capacity to undertake the neuropsychological tests.
- Positive assessment of the candidate by the investigator for complying with the requirements and procedures of the study.
Exclusion Criteria:
- Pregnant women or women of child-bearing age.
- Patients whose general state of health was such that it did not allow completion of the trial or that made taking part in the trial difficult, as judged by the investigator.
- Participation in another clinical trial in the 3 months prior to visit 0 or during the 12 months prior to the selection visit in the case of patients who had participated in trials where the study drug was aimed at modifying the progression of AD.
Known allergy to the vaccine components or history of anaphylaxis, severe allergic reaction or history of hypersensitivity to any of the components of the formulation.
Allergy to fish or shellfish.
- Absolute (having a pacemaker or implantable defibrillator) or relative (bare metal stent or stent implanted in the last 6 months) contraindications to MRI examination.
- Surgery (with general anesthetic) during the 3 months prior to admission into the study and/or surgery planned at any point during the study period.
- History or presence of autoimmune disease.
- Presence or history of immunodeficiency (e.g. HIV).
Recent history of cancer (≤3 years since the last specific treatment). (Exceptions:
basal-cell carcinoma, intraepithelial cervical neoplasia).
- Active infectious disease (e.g. hepatitis B, C) or history of chronic viral hepatitis or other chronic hepatic disorders.
- Major systemic condition (e.g. chronic renal failure, chronic hepatopathy, uncontrolled diabetes, uncontrolled congestive heart failure, other deficiencies).
- History of asthma or reactive airway disease presenting as bronchospasm in the last 6 months or currently on a regular anti-asthmatic drug treatment.
- Poorly controlled diseases like poorly controlled hypertension (systolic arterial tension >160 mmHg or diastolic arterial tension >100 mmHg, as an average of 3 measurements) or poorly controlled diabetes according to the investigator's opinion (HbA1c > 12.0).
- Significant alterations in hematological, biochemical or urine analytical parameters, particularly those relating to levels of vitamin B12, folic acid or thyroid tests, and including the possibility of clinically significant anemia.
- Hypothyroidism, defined as any major alteration in thyrotropin (TSH). Patients with corrected hypothyroidism could participate in the study providing that treatment had remained stable for three months immediately prior to admission to the study, and provided that it was ruled out as the cause of or as contributing to the severity of the subject's dementia.
- Positive serology for syphilis (except where neurosyphilis had previously been ruled out).
- History of major psychiatric illness such as schizophrenia, bipolar disorder or major depressive disorder during the last year [according to Diagnostic and Statistical Manual of Mental Disorders (DSM) -IV criteria)].
- Metabolic or toxic encephalopathy or dementia due to a general medical illness.
- Abuse or excessive consumption of alcohol or drugs according to the DSM-IV criteria.
- Wernicke's encephalopathy.
- History or indications of any other Central Nervous System (CNS) disorder that could be the cause of the dementia (demyelinating, or infectious or inflammatory CNS disease, Creutzfeldt- Jakob disease, Parkinson's disease, Huntington's disease, brain tumor, subdural hematoma, etc.).
- History or indications of cerebrovascular disease (ischemic or hemorrhagic ictus, transient ischemic attack), or diagnosis of possible, probable or definite vascular dementia according to NINDS- Association Internationale pour la Recherché et l'Enseignement en Neurosciences (AIREN) criteria.
- History of intracerebral hemorrhage caused by any of the following: cerebral amyloid angiopathy, uncontrolled hypertension, cerebral arteriovenous malformation, coagulopathy, CNS vasculitis or any other pathology considered by the investigator and/or medical monitor to be a risk factor for intracerebral hemorrhage.
- Prior or current treatment with experimental immunotherapies, including Intravenous Immunoglobulin (IVIG) or vaccines against AD.
- Treatment with systemic corticosteroids or other immunosuppressants during the 30 days prior to visit 0.
- Change in treatments doses for AD or hypothyroidism during the 3 months prior to visit 0.
- Change in dose of drugs for concurrent illnesses appearing in the patient's clinical history during the 30 days prior to visit 1, if they were clinically relevant.
- Patients who had been previously included in the trial, except those patients who failed the screening for reasons that had since been resolved, and so their re-entry into the trial could be considered. Those who received their randomization number and then left the trial remained excluded.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ABvac40
Placebo
Arm Description
Outcomes
Primary Outcome Measures
number of participants with adverse events
frequency of adverse events; overall and grouped as neurological, psychiatric and cardiovascular.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03113812
Brief Title
Repeated Subcutaneous Administration of ABvac40 in Mild to Moderate Alzheimer's Disease Patients
Official Title
A Randomized, Placebo-controlled, Parallel Group, Double-blinded, Single-center Phase-I, Pilot Study to Assess Tolerability and Safety of Repeated Subcutaneous Administration of ABvac40 in Patients With Mild to Moderate Alzheimer's Disease.
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
January 1, 2014 (Actual)
Primary Completion Date
July 30, 2015 (Actual)
Study Completion Date
July 30, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Araclon Biotech S.L.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This first time study in humans was designed to assess tolerability and safety of repeated subcutaneous injections of ABvac40, an active immunization against the C-terminal end of Abeta1-40.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ABvac40
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
ABvac40
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
number of participants with adverse events
Description
frequency of adverse events; overall and grouped as neurological, psychiatric and cardiovascular.
Time Frame
up to week 16
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Clinical diagnosis suggesting Alzheimer's disease (AD) based on the criteria of the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA).
The results of the patient's MRI brain scan had to be concordant with the diagnosis of AD according to the following criteria: Scheltens scale, and quantitative measurement of white matter and past hemorrhages.
Severity of Alzheimer's disease (AD) assessed as mild or moderate using the Mini Mental State Examination (MMSE) scale. Mild or moderate AD was confirmed if the MMSE score varied between 15 and 26.
The Hachinski ischemic scale was used to distinguish AD from multi-infarct dementia. A score of ≤4 suggested AD.
Score on the Clinical Dementia Rating Scale (CDR) of 0.5 or 1.0.
Be receiving a stable dose of treatment for AD for three months before the selection visit, and expecting to continue treatment for the duration of the study (if appropriate).
Stable treatment for other illnesses may be administered 30 days prior to V0 (selection).
Males or females from 50 to 85 years of age, inclusive (at the time of signing informed consent).
The patient (or a close relative or legal representative) should read the patient information sheet, agreed to participate in the clinical trial and signed Inform consent (IC) (the patient and a close relative or legal representative).
Presence of a stable caregiver willing to attend patient visits during the study.
Sufficient visual and auditory capacity to undertake the neuropsychological tests.
Positive assessment of the candidate by the investigator for complying with the requirements and procedures of the study.
Exclusion Criteria:
Pregnant women or women of child-bearing age.
Patients whose general state of health was such that it did not allow completion of the trial or that made taking part in the trial difficult, as judged by the investigator.
Participation in another clinical trial in the 3 months prior to visit 0 or during the 12 months prior to the selection visit in the case of patients who had participated in trials where the study drug was aimed at modifying the progression of AD.
Known allergy to the vaccine components or history of anaphylaxis, severe allergic reaction or history of hypersensitivity to any of the components of the formulation.
Allergy to fish or shellfish.
Absolute (having a pacemaker or implantable defibrillator) or relative (bare metal stent or stent implanted in the last 6 months) contraindications to MRI examination.
Surgery (with general anesthetic) during the 3 months prior to admission into the study and/or surgery planned at any point during the study period.
History or presence of autoimmune disease.
Presence or history of immunodeficiency (e.g. HIV).
Recent history of cancer (≤3 years since the last specific treatment). (Exceptions:
basal-cell carcinoma, intraepithelial cervical neoplasia).
Active infectious disease (e.g. hepatitis B, C) or history of chronic viral hepatitis or other chronic hepatic disorders.
Major systemic condition (e.g. chronic renal failure, chronic hepatopathy, uncontrolled diabetes, uncontrolled congestive heart failure, other deficiencies).
History of asthma or reactive airway disease presenting as bronchospasm in the last 6 months or currently on a regular anti-asthmatic drug treatment.
Poorly controlled diseases like poorly controlled hypertension (systolic arterial tension >160 mmHg or diastolic arterial tension >100 mmHg, as an average of 3 measurements) or poorly controlled diabetes according to the investigator's opinion (HbA1c > 12.0).
Significant alterations in hematological, biochemical or urine analytical parameters, particularly those relating to levels of vitamin B12, folic acid or thyroid tests, and including the possibility of clinically significant anemia.
Hypothyroidism, defined as any major alteration in thyrotropin (TSH). Patients with corrected hypothyroidism could participate in the study providing that treatment had remained stable for three months immediately prior to admission to the study, and provided that it was ruled out as the cause of or as contributing to the severity of the subject's dementia.
Positive serology for syphilis (except where neurosyphilis had previously been ruled out).
History of major psychiatric illness such as schizophrenia, bipolar disorder or major depressive disorder during the last year [according to Diagnostic and Statistical Manual of Mental Disorders (DSM) -IV criteria)].
Metabolic or toxic encephalopathy or dementia due to a general medical illness.
Abuse or excessive consumption of alcohol or drugs according to the DSM-IV criteria.
Wernicke's encephalopathy.
History or indications of any other Central Nervous System (CNS) disorder that could be the cause of the dementia (demyelinating, or infectious or inflammatory CNS disease, Creutzfeldt- Jakob disease, Parkinson's disease, Huntington's disease, brain tumor, subdural hematoma, etc.).
History or indications of cerebrovascular disease (ischemic or hemorrhagic ictus, transient ischemic attack), or diagnosis of possible, probable or definite vascular dementia according to NINDS- Association Internationale pour la Recherché et l'Enseignement en Neurosciences (AIREN) criteria.
History of intracerebral hemorrhage caused by any of the following: cerebral amyloid angiopathy, uncontrolled hypertension, cerebral arteriovenous malformation, coagulopathy, CNS vasculitis or any other pathology considered by the investigator and/or medical monitor to be a risk factor for intracerebral hemorrhage.
Prior or current treatment with experimental immunotherapies, including Intravenous Immunoglobulin (IVIG) or vaccines against AD.
Treatment with systemic corticosteroids or other immunosuppressants during the 30 days prior to visit 0.
Change in treatments doses for AD or hypothyroidism during the 3 months prior to visit 0.
Change in dose of drugs for concurrent illnesses appearing in the patient's clinical history during the 30 days prior to visit 1, if they were clinically relevant.
Patients who had been previously included in the trial, except those patients who failed the screening for reasons that had since been resolved, and so their re-entry into the trial could be considered. Those who received their randomization number and then left the trial remained excluded.
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
29378651
Citation
Lacosta AM, Pascual-Lucas M, Pesini P, Casabona D, Perez-Grijalba V, Marcos-Campos I, Sarasa L, Canudas J, Badi H, Monleon I, San-Jose I, Munuera J, Rodriguez-Gomez O, Abdelnour C, Lafuente A, Buendia M, Boada M, Tarraga L, Ruiz A, Sarasa M. Safety, tolerability and immunogenicity of an active anti-Abeta40 vaccine (ABvac40) in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase I trial. Alzheimers Res Ther. 2018 Jan 29;10(1):12. doi: 10.1186/s13195-018-0340-8.
Results Reference
derived
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Repeated Subcutaneous Administration of ABvac40 in Mild to Moderate Alzheimer's Disease Patients
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