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

• ClinicalTrials.gov Identifier: NCT05328115
• Recruitment Status: Recruiting
• First Posted: April 14, 2022
• Last Update Posted: June 13, 2022
• Sponsor: Alzinova AB
• Collaborator: CRST Oy
• Information provided by (Responsible Party): Alzinova AB

Study Description

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 disease are randomised into two arms of active treatment and one of placebo. Patients are given four doses during 5 months and then followed up for 13 months.

Condition or disease	Intervention/treatment	Phase
Alzheimer Disease	Biological: ALZ-101; Other: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Randomized, Parallel-group Multiple Dose Study on the Safety, Tolerability and Immunogenicity of ALZ-101 in Participants With Early Alzheimer's Disease
• Actual Study Start Date: September 30, 2021
• Estimated Primary Completion Date: July 31, 2023
• Estimated Study Completion Date: July 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: ALZ-101 125 μg; Intra muscular injection of 125 μg of ALZ-101 adjuvanted vaccine dosed once a month at four doses	Biological: ALZ-101; Intramuscular injections of adjuvanted peptide vaccine against oligomeric Amyloid Beta.
Active Comparator: ALZ-101 250 μg; Intra muscular injection of 250 μg of ALZ-101 adjuvanted vaccine dosed once a month at four doses	Biological: ALZ-101; Intramuscular injections of adjuvanted peptide vaccine against oligomeric Amyloid Beta.
Placebo Comparator: Placebo; Saline solution mixed adjuvant and dosed once a month at four doses	Other: Placebo; Intramuscular injections of adjuvanted placebo.

Outcome Measures

Primary Outcome Measures :

1. Number of adverse events (AEs) and serious AEs (SAEs) [ Time Frame: From enrolment through study completion, an average 1 year ]
   Any adverse or serious adverse events that could be associated with the study procedure.
2. Number of participants with treatment-emergent AEs and SAEs [ Time Frame: From enrolment through study completion, an average 1 year ]
   Any adverse or serious adverse events that could be associated with the treatment.
3. Number of AEs of special interest (AESIs), including injection-related events (IREs)and amyloid-related imaging abnormalities (ARIAs) [ Time Frame: From enrolment through study completion, an average 1 year ]
   Any adverse or adverse events of special interest that could be associated with the treatment.
4. 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 [ Time Frame: From first dose to study completion, an average 1 year ]
   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.

Secondary Outcome Measures :

1. Aβ-specific antibody titre [ Time Frame: From first dose to study completion, an average 1 year ]
   Aβ-specific antibody titre of post-baseline samples (if baseline sample is negative) OR titre fold increase defined as the ratio of any post-baseline Aβ-specific antibody titre to baseline antibody titre in serum
2. Number of titre-based responders [ Time Frame: From first dose to study completion, an average 1 year ]
   Number of titre-based responders, defined as post-baseline sample becoming positive for Aβ-specific antibodies(if baseline sample is negative) OR post-baseline titre at least four times the baseline antibody titre in serum
3. Area under serum Aβ-specific antibody titre curve (AUC) [ Time Frame: From first dose to week 20 ]
   Area under serum Aβ-specific antibody titre curve (AUC) from Week 0 to Week 20.
4. Maximum titre level (Cmax) [ Time Frame: From first dose to week 20 ]
   Plasma concentration of Aβ-specific antibodies at their maximum titre level.
5. Time to Cmax(tmax) [ Time Frame: From first dose to week 20 ]
   Time to maximum titre levels of plasma Aβ-specific antibodies.

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male and female subjects between 50 and 80 years(inclusive) of age at the time of informed consent
2. 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)

3. Subjects with mild cognitive impairment(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:

   1. Clinical dementia rating(CDR) global score(GS) of 0.5 or 1
   2. CDR memory score of ≥0.5c. Mini mental state examination(MMSE) score of ≥20 points
4. Screening cerebro-spinal fluid (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 Aβ42/40ratio (cut-off level set by the laboratory)
5. 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 investigational medicinal product(IMP). Treatment-naïve subjects may also be entered into the study
6. 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)

Exclusion Criteria:

1. 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
2. Screening MRI(3T)results showing evidence of clinically significant pathological lesions that could indicate a dementia-associated diagnosis other than early AD or cause a safety risk for the participant(a list of possible exclusionary findings is included in the main protocol text)
3. Modified Hachinski Ischemia Score (mHIS) >4 at screening
4. History of a cerebrovascular incident, including transient ischemic attack(TIA) or stroke, within 12 months of screening
5. Subject with a history of seizures within 5 years of screening
6. 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 Diagnostic and Statistical Manual(DSM)-5 criteria for major depression at screening
7. 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
8. Disorder related to alcohol or drug abuse, as defined in DSM-5, within 5 years prior to screening
9. 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
10. 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
11. Evidence of current clinically significant and possibly unstable pulmonary, gastrointestinal, renal, hepatic, endocrine, hematological or cardiovascular system disease or metabolic disturbance
12. 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

13. 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:

    1. estimated glomerular filtration ratio (eGFR) <30 ml/min/1.73m2, based on the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI) equation
    2. plasma total bilirubin value >2 times the upper limit of the reference range
    3. plasma alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) value >2 times the upper limit of the reference range
    4. low vitamin B12 or folate values that are considered to be clinically significant in relation to cognitive impairment. In such cases, re-screening is permissible after supplementation therapy has been provided for a sufficient time
    5. prolonged QT corrected for heart rate by Fridericia's cube root formula(QTcF) interval of >470 ms
14. Clinically suspected active neuroborreliosis, confirmed by the presence of Borrelia antibodies in CSF

15. Contraindication to lumbar puncture (LP). These contraindications may include, but are not limited to, the following:

    1. increased intracranial pressure (ICP)
    2. skin infection at the LP site
    3. significant lumbar spine deformity
    4. bleeding diathesis (e.g., significant thrombocytopenia)
    5. taking anticoagulant therapy (e.g., warfarin, dabigatran, apixaban, or other blood factor or thrombin inhibitor). Use of anti-platelet therapy(e.g. low-dose aspirin) may be permitted if deemed appropriate in the Investigator's judgement
16. Current or anticipated use,or recent prior use (pre-study time limits specified in the main protocol text) of disallowed concomitant treatment
17. Any vaccination within 2weeks prior to screening
18. History of severe drug allergy (anaphylactic shock or drug-induced hypersensitivity syndrome), or known hypersensitivity to vaccines, including constituents of vaccines

19. Having received in another clinical trial

    1. any therapeutic monoclonal antibody, protein derived from a monoclonal antibody or immunoglobulin therapy within 6 months before screening
    2. active anti-amyloid immunization or other active immunization for the treatment of AD
    3. any other investigational medication (unless it can be documented that the subject received only placebo) or device within 3 months or 5 half-lives(which ever is longer) before screening
20. Any condition that may be contributing to cognitive impairment above and beyond that caused by the subject's early AD
21. Disease or medication that, in the opinion of the Investigator, could interfere with the assessments of safety, tolerability or immunogenicity
22. Planned surgery requiring general, spinal or epidural anaesthesia that would take place during the study. Planned surgery requiring only local anaesthesia need not result in exclusion, if in the opinion of the Investigator this operation does not interfere with study procedures and participant safety
23. Female subjects of childbearing potential(defined in detail in the main protocol text)

Contacts and Locations

Contacts

Contact: Stefan Pierrou, PhD; +46708123615; Stefan.Pierrou@alzinova.com

Contact: Kristina Torfgård, PhD; +46 708 467975; kristina.torfgard@alzinova.com

Locations

Finland

Clinical Research Services Turku -CRST Oy; Recruiting

Turku, Finland, FI-20520

Contact: Juha Rinne, MD +358 23131866 juha.rinne@crst.fi

Contact: Zsofia Lovro, MD +358 45 896 6565 zsofia.lovro@crst.fi

Sponsors and Collaborators

Alzinova AB

CRST Oy

Investigators

• Principal Investigator: Juha Rinne, MD; CRST Oy

More Information

• Responsible Party: Alzinova AB
• ClinicalTrials.gov Identifier: NCT05328115
• Other Study ID Numbers: ALZ-C-001; 2019-002277-62 ( EudraCT Number )
• First Posted: April 14, 2022
• Last Update Posted: June 13, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

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