A Study on the Safety, Tolerability and Immunogenicity of ALZ-101 in Participants With Early Alzheimer's Disease

NCT05328115 | Completed Phase 1

• 2 other identifiers: ALZ-C-0012019-002277-62
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to evaluate safety, tolerability and immunogenicity of the vaccine ALZ-101 against Alzheimer's Disease. Patients diagnosed with early Alzheimer's will be included. The study have two parts. The Part A (including A1 and A2), includes four doses of ALZ-101 or corresponding placebo given over 16 weeks. Participant will be followed up to Week 30 in Part A1 and either continue in the extension part of the study, Part B, or complete Part A1. Participant not eligible to Part B will be followed up until Week 68 with no further dosing. Participant eligible for Part B will be treated with 2 doses of open-label ALZ-101, over 16 weeks and followed up during in total 68 weeks (Part A1 and B). Part A2 participants will be followed over 20 weeks.

Conditions

Alzheimer Disease; Dementia Alzheimers; Dementia, Mild

Outcome Measures

Primary Outcomes (4)

• Number of adverse events (AEs) and serious AEs (SAEs)

  Any adverse or serious adverse events that could be associated with the study procedure.

  From enrolment through study completion, an average 1 year

• Number of participants with treatment-emergent AEs and SAEs

  Any adverse or serious adverse events that could be associated with the treatment.

  From enrolment through study completion, an average 1 year

• Number of AEs of special interest (AESIs), including injection-related events (IREs)and amyloid-related imaging abnormalities (ARIAs)

  Any adverse or adverse events of special interest that could be associated with the treatment.

  From enrolment through study completion, an average 1 year

• Number of participants with clinically significant cognitive or functional worsening of Alzheimer's Disease(AD) according to Alzheimer's DiseaseCooperative Study -Clinician's Global Impression of Change (ADCS-CGIC)scores of 6 and 7

  Any clinically significant worsening of cognitive functions as assessed by Alzheimer's DiseaseCooperative Study -Clinician's Global Impression of Change \[ADCS-CGIC\]scores. Scores are graded from 1 to 7, where 1 means very much improved cognitive function and 7 very much worsening cognitive function.

  From first dose to study completion, an average 1 year

Secondary Outcomes (3)

• Aβ-specific antibody titre

  From first dose to study completion, an average 1 year

• Number of titre-based responders

  From first dose to study completion, an average 1 year

• Area under serum Aβ-specific antibody titre curve (AUC)

  From first dose to week 20

Study Arms (4)

ALZ-101 125 μg

ACTIVE COMPARATOR

Intramuscular injection of 125 μg of ALZ-101 adjuvanted vaccine dosed once a month at four doses

Biological: ALZ-101

ALZ-101 250 μg

ACTIVE COMPARATOR

Intramuscular injection of 250 μg of ALZ-101 adjuvanted vaccine dosed once a month at four doses

Biological: ALZ-101

Placebo

PLACEBO COMPARATOR

Intamuscular Saline solution mixed adjuvant and dosed once a month at four doses

Other: Placebo

ALZ-101 400 μg

ACTIVE COMPARATOR

Intramuscular injection of 400 μg of ALZ-101 adjuvanted vaccine dosed once a month at four doses

Biological: ALZ-101

Interventions

ALZ-101 BIOLOGICAL

Intramuscular injections of adjuvanted peptide vaccine against oligomeric Amyloid Beta.

ALZ-101 125 μg; ALZ-101 250 μg; ALZ-101 400 μg

Placebo OTHER

Intramuscular injections of adjuvanted placebo.

Placebo

Eligibility Criteria

• Age: 50 Years - 83 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects between 50 and 83 years (inclusive) of age at the time of informed consent
• Subjects capable of providing valid independent informed consent and signing the informed consent form (the subjects' capacity to provide valid consent should be determined in accordance with applicable professional standards, and will be based on the Investigator's judgement)
• Subjects with MCI due to AD or mild AD according to National Institute of Aging - Alzheimer's Association (NIA-AA) core clinical criteria; subjects must have all of the following at screening:
• CDR global score (GS) of 0.5 or 1
• CDR memory score of ≥0.5
• MMSE score of ≥20 points
• Screening CSF results showing a pattern consistent with amyloid plaque load and indicative of AD pathology. The CSF results will be evaluated by the Investigator and will take into account the Aβ42/40 ratio (cut-off level set by the laboratory)
• If the subject is receiving an acetylcholine esterase inhibitor (AChEI) or memantine or both for the treatment of MCI or AD, this treatment must be on a stable dosage for at least 8 weeks prior to the first dosing of IMP. Treatment-naïve subjects may also be entered into the study
• Subjects must have an identified, reliable and knowledgeable study partner who is willing and able to support the participant and to provide follow-up information on the study participant throughout the course of the study. This person must, in the opinion of the Investigator, spend sufficient time with the study participant on a regular basis such that he or she can reliably fulfil the requirements of being a study partner (however, a study partner does not need to be living in the same household with the study participant)
• Male and female subjects who have completed Visit 15 of Part A and are willing to continue in Part B of the study
• Subjects providing informed consent and signing the informed consent form. In case a subject is considered not to be capable of providing valid independent informed consent, the subject's legally acceptable representative (LAR) should consent to the study on behalf of the subject. In such a case, the subject should provide informed assent to continue in the study
• Subjects must have an identified, reliable and knowledgeable study partner who is willing and able to support the participant and to provide follow-up information on the study participant throughout the course of the study. This person must, in the opinion of the Investigator, spend sufficient time with the study participant on a regular basis such that he or she can reliably fulfil the requirements of being a study partner.

You may not qualify if:

• Subjects having any contraindication to MRI scanning; or are unable to undergo brain MRI scanning according to the standard criteria of the MRI unit; or the Investigator believes that the subject will not be able to undergo further scans scheduled during the course of the study
• Modified Hachinski Ischemia Score (mHIS) \>4 at screening
• History of a cerebrovascular incident, including transient ischemic attack (TIA) or stroke, within 12 months of screening
• Subject with a history of seizures within 2 years of screening
• Any psychiatric diagnosis or symptoms (e.g. hallucinations, major depression, delusions, schizophrenia, bipolar disorder) that, in the opinion of the Investigator, could interfere with study procedures or assessments or participant safety. A subject with depression may, however, be included if treated with a stable dose of antidepressants for at least 8 weeks before screening and not fulfilling DSM-5 criteria for major depression at screening
• Significant risk of suicide (defined using the Columbia Suicide Severity Scale \[C-SSRS\], with the subject answering "yes" to suicidal ideation questions 4 or 5 or answering "yes" to suicidal behaviour) within 12 months of screening
• Disorder related to alcohol or drug abuse, as defined in DSM-5, within 2 years prior to screening
• Evidence of current or history of any significant autoimmune disease that, in the opinion of the Investigator, could interfere with evaluation of the study results or constitute a health hazard for the subject
• Evidence of an immune system that is compromised; including, but not limited to, a diagnosis of HIV (human immunodeficiency virus); or the subject has been splenectomised or has received an organ transplant (corneal transplants excluded), or is receiving chronic systemic immunosuppressive medication
• Evidence of current clinically significant and possibly unstable pulmonary, gastrointestinal, renal, hepatic, endocrine, hematological or cardiovascular system disease or metabolic disturbance
• Diagnosis of cancer (hematological or solid tumor) for which the subject is currently being treated, or for which there has been treatment within 5 years preceding screening, or for which there is still evidence of active disease. Subjects with local prostate cancer or local dermatological tumors, such as basal or squamous cell carcinoma, may be included
• Any clinically significant abnormalities in laboratory tests, vital signs, ECG or physical examination findings at screening that in the opinion of the Investigator require further investigation or treatment, or may interfere with study procedures or safety. These may include, but are not limited to, the following:
• estimated glomerular filtration ratio (eGFR) \<30 ml/min/1.73 m2, based on the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation
• plasma total bilirubin value \>2 times the upper limit of the reference range
• plasma alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) value \>2 times the upper limit of the reference range

Sponsors & Collaborators

• Alzinova AB: lead
• CRST Oy: collaborator

Study Sites (1)

Clinical Research Services Turku -CRST Oy

Turku, FI-20520, Finland

Location

MeSH Terms

Conditions

Alzheimer Disease; Dementia; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Juha Rinne, MD

  CRST Oy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The arm with ALZ-101 400 μg will be open-labelled treatment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2022
• First Posted: April 14, 2022
• Study Start: September 30, 2021
• Primary Completion: January 27, 2025
• Study Completion: January 27, 2025
• Last Updated: January 31, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1)