Alzheimer Disease
Conditions
Brief summary
ALZN002-01 is a first-in-human, randomized, double-blind, placebo-controlled, parallel-group, phase 1/2a study of autologous amyloid beta mutant peptide-pulsed dendritic cells (ALZN002) in subjects with mild-to-moderate dementia of the Alzheimer's type.
Detailed description
ALZN002-01 is a first-in-human, randomized, double-blind, placebo-controlled, parallel-group, phase 1/2a study. The primary purpose of this study is to assess the safety and tolerability of multiple ascending doses of ALZN002 compared with that of placebo in subjects with mild to moderate dementia of the Alzheimer's type (AD) and to determine the optimal dosage of ALZN002 that allows for induction of anti-amyloid-beta (Aβ) antibody responses while maintaining safety. The overall goal of this study is to determine an appropriate dose to use in a larger phase 2b study (ALZN002-02) where efficacy is the primary study purpose.
Interventions
BIOLOGICALALZN002 (autologous DCs pulsed with E22W mutant peptide).
The cellular immunotherapy product consists of autologous dendritic cells (DCs) pulsed with a novel amyloid-beta peptide (Aβ1 42) containing a mutation at position 22 from glutamic acid to tryptophan (E22W). This mutation produces novel CD4+ T cell epitopes specific for the mutant E22W peptide that can facilitate an anti-Aβ1-42 antibody response. The activated E22W peptide specific CD4+ T cells license Aβ1-42-specific B cells to secrete anti Aβ1-42 antibodies, resulting in systemic reduction of amyloid and reduction or slowed accumulation of amyloid plaques in the brain.
DRUGPlacebo
Saline
Sponsors
bioRASI, LLC
Alzamend Neuro, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Each cohort will have 10 total subjects randomized in a 7:3 ratio (active:placebo). Subjects will be randomly allocated to treatment groups based on a central computer-generated randomization scheme.
Eligibility
Sex/Gender
ALL
Age
60 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Potential study subjects must satisfy the following criteria to be randomized in the study: 1. Age ≥60 and ≤85 years with no restrictions on gender, race, or ethnicity. 2. Able and willing to give informed consent and adhere to study requirements, including testing for cognitive and functional abilities. 3. Confirmation of AD at Screening based either on a positive amyloid PET obtained at Screening or based on historical positive amyloid PET taken within 6 months prior to the screening visit consistent with AD. If historical amyloid PET imaging is used for inclusion 1. there should be no clinically significant change in the subject's symptoms and cognitive abilities within the 6 months prior to Screening. 2. The quality and accuracy of the historical positive amyloid PET needs to be confirmed by the central imaging center 4. Willing and able to have amyloid PET taken at Screening (if no historical adequate amyloid PET within 6 months of Screening is available) to confirm AD and at Week 31 and Week 143 as a potential efficacy measure. 5. Willing and able to have magnetic resonance imaging (MRI) taken at Screening, at 1 year (Week 55) and 2 years (Week 101) after the 3rd dose, and at 1 year after the 10th dose (Week 143/EOS) as potential safety measures. 6. Males (non-vasectomized and vasectomized) must agree to use barrier contraception during the study until 30 days after the last dose of the study investigational treatment. 7. Females must meet one the of the following criteria: a. Either is of childbearing potential and agrees to use an acceptable contraceptive method. Acceptable contraceptive methods include: i. Abstinence from heterosexual intercourse from the Screening visit through to at least 30 days after the last dose of the study investigational treatment ii. One of the following highly-effective contraceptive methods, used from at least 28 days prior to the Screening visit through to at least 30 days after the last dose of the study investigational treatment: * Systemic contraceptive (combined birth control pills, injectable/implant/insertable hormonal birth control products, or transdermal patch) * Intrauterine device (with or without hormones) * Male condom used with male partner vasectomized at least 6 months prior to the Screening visit iii. One of the following double-barrier contraceptive methods, used from the Screening visit through to at least 30 days after the last dose of the study investigational treatment: * Male condom used simultaneously with diaphragm plus spermicide * Male condom used simultaneously with cervical cap plus spermicide Or b. Is of non-childbearing potential, defined as surgically sterile (ie, has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation), or is in a postmenopausal state (ie, at least 1 year without menses, not attributable to another cause, prior to the Screening visit) 8. In the event that the subject requires a study partner, he/she must be reliable and will provide written informed consent to participate and be in frequent contact with the participant. The study partner must be familiar with the subject's overall function and behavior, such as day-to-day activities and cognitive abilities. 9. Able to speak, read, and write (for cognitive testing). 10. Clinical diagnosis of probable or possible AD based on National Institute on Aging - Alzheimer's Association (NIA-AA) criteria by a qualified clinician. 11. Clinical diagnosis of at least mild dementia according to the CDR Global Score of 0.5 to 2 at screening and Baseline 12. Mini-Mental State Examination (MMSE) score of 14 - 26 and ADAS-cog11 score greater than 12 at screening and Baseline. 13. Willing and able to undergo leukapheresis as needed. 14. Consent to undergo d HLA geno-typing and PaxGene RNA.
Exclusion criteria
Subjects who meet any of the following criteria will be excluded from participating in the study: 1. Prior immunotherapies and specifically therapies that may elicit T cell or antibody responses to Aβ, whether investigational or approved by the FDA, for AD or other conditions. 2. Central nervous system-related exclusions: 1. Delirium, non-AD dementia or cognitive impairment, or other encephalopathies. 2. Subjects with major psychiatric disorder such as schizophrenia, bipolar disorder or major depressive disorder, or has current alcohol or substance abuse based on psychiatric consultation at Screening visit. 3. Neuropsychiatric Inventory (NPI-Q) total score ≥14 or score ≥4 in any NPI domain (clinically significant neuropsychiatric symptoms). Apathy score ≥4 acceptable. 4. At risk for suicide in the opinion of the investigator or the subject answers yes to Suicidal Ideation Item 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) (at the time of evaluation) at the screening visit or attempted suicide within the last 2 years. 5. Modified Hachinski Scale10 score \>4 or evidence of stroke within the past 5 years. 6. Neuroimaging exclusions by history or entry criteria: Arteriovenous malformation, brain mass, suggestive changes of cerebral amyloid angiopathy (CAA), aneurysms, or other changes that increase risk of hemorrhage, multiple cerebral macrohemorrhages, or other cerebrovascular complications as deemed by the Principal Investigator and/or the Safety Adjudication Committee that might account for cognitive symptoms. 7. MRI-related
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TEAEs | Through study completion, up to 33 months | Frequency and severity of TEAEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study Completion | Through study completion, up to 33 months | Proportion of subjects completing the study |
| Number of Participants with changes from baseline in safety laboratory values. | Through study completion, up to 33 months | The number of participants with changes from baseline in the following safety laboratory values: CMP, Hematology (CBC with differential), TSH, Vitamin B12, CRP, Liver Function Test, and Urinalysis will be presented. |
| Number of Participants with changes from baseline in blood pressure. | Through study completion, up to 33 months | The number of participants with clinically significant abnormalities in blood pressure from baseline will be presented. |
| Number of Participants with changes from baseline in heart rate. | Through study completion, up to 33 months | The number of participants with clinically significant abnormalities in heart rate from baseline will be presented. |
| Number of Participants with changes from baseline in oxygen saturation. | Through study completion, up to 33 months | The number of participants with clinically significant abnormalities in oxygen saturation from baseline will be presented. |
| Number of Participants with changes from baseline in oral temperature. | Through study completion, up to 33 months | The number of participants with clinically significant abnormalities in oral temperature from baseline will be presented. |
| SAEs | Through study completion, up to 33 months | Frequency and severity of serious adverse events (SAEs) |
| DTH Response | Through study completion, up to 21 months | Frequency of a delayed-type hypersensitivity (DTH) response at the ID injection site. |
| Infusion Reactions | Through study completion, up to 21 months | Frequency of acute infusion reactions. |
| Anti-Aβ1-42 antibody titer | Through study completion, up to 33 months | Evaluation of the anti-Aβ1-42 antibody titer at all collection visits during the study. |
| Proportion of subjects with anti-Aβ antibodies | Through study completion, up to 33 months | Proportion of subjects with anti-Aβ antibodies at all collection visits during the study and by visit. |
| Proportion of subjects with isotype of anti-Aβ antibodies | Through study completion, up to 33 months | Proportion of subjects with isotype of anti-Aβ antibodies by visit. |
| Number of Participants with changes from baseline in 12-lead ECG findings. | Through study completion, up to 33 months | The number of participants with clinically significant abnormalities in 12-lead ECG will be presented. Individual parameters that will be collected include heart rate, PR, QT, QTcF, QRS, and PR intervals. |
Countries
United States
Outcome results
None listed