Multiple Ascending Dose Safety, Tolerability, PK Study of AL001 in Alzheimer's Disease Patients & Healthy Adult Subjects

NCT05363293 | Completed Phase 1 Results FDA Drug

• 1 other identifier: AL001-ALZ02
• Study Type: interventional
• Target: 65
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a Phase 1/2a, multi-center, placebo-controlled, double-blinded, randomized, multiple ascending dose (MAD) clinical trial to determine the safety and maximum tolerated dose of AL001. Up to 72 participants will be randomly assigned to receive study drug (active AL001) or placebo. The study consists of a 4-week screening period, a 14-day treatment period, and a 42-day follow-up period.

Conditions

Alzheimer's Disease; Healthy Non-elderly and Elderly Adults

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Serious AEs, TEAEs That Lead to Premature Discontinuation, Abnormal Laboratory Test Results, Abnormal ECG Readings.

  To evaluate the safety and tolerability of AL001 in healthy subjects and patients with adverse event(s), AD, descriptive statistics will be presented by treatment group for each cohort and overall, for the following: Proportion of participants with treatment-emergent adverse events (TEAEs) * Proportion of participants with serious AEs * Proportion of participants with TEAEs that lead to premature discontinuation * Proportion of participants with abnormal values for each safety laboratory test (change from baseline) * Proportion of participants with abnormal values for each Electrocardiogram (ECG) parameter (change from baseline in standard 12-lead ECG parameters) For all analyses, placebo-treated subjects from each Cohort were combined (pooled) to provide a composite placebo group for all comparisons. Adverse event profiles for all treated subjects were benign as were placebo-treated subjects. No further statistical analyses were therefore appropriate.

  42 days with a 14-day treatment period

Secondary Outcomes (2)

• Maximum Tolerated Dose of AL001 (Lithium Component) in All Subjects Treated With AL001

  42 days with a 14-day treatment period

• Maximum Tolerated Dose of AL001 (Salicylate Component) in All AL001-treated Subjects

  42 days with a 14-day treatment period

Study Arms (9)

Multiple Ascending Doses of AL001 vs. Placebo - Cohort 1

EXPERIMENTAL

Participants will be randomized to receive AL001. When adequate safety data are available, a review will be done for all participants to make a dose-escalation or dose and/or regimen modification decision. This will be repeated for each cohort. A total of 9 cohorts will receive 5 different dose levels of AL001 in multiple ascending doses under fasted conditions up to tolerability/safety limits. Cohort 1 will include 8 AD subjects. In this cohort, 6 active and 2 placebo AD subjects (as per randomization code) will receive the following treatment or placebo: • Cohort 1: 60% of 450 mg lithium carbonate equivalent of AL001 (1890 mg AL001 daily ×14 days, given as 3 × 210 mg AL001 capsules TID)

Drug: AL001; Other: Placebo

Multiple Ascending Doses of AL001 vs. Placebo - Cohorts 2a

EXPERIMENTAL

The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated. Cohort 2a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults). Per randomization, there will be 6 active and 2 placebo subjects in each cohort: • Cohort 2a: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID).

Drug: AL001; Other: Placebo

Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3a

EXPERIMENTAL

The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated. Cohort 3 will be sub-divided into 2 cohorts: Cohort 3a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults) and Cohort 3b (8 AD subjects). Per randomization, there will be 6 active and 2 placebo subjects in each cohort: • Cohort 3a and 3b: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID)

Drug: AL001; Other: Placebo

Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4a

EXPERIMENTAL

The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated. Cohort 4a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults). Per randomization, there will be 6 active and 2 placebo subjects in each cohort: • Cohort 4a: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID)

Drug: AL001; Other: Placebo

Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5a

EXPERIMENTAL

The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated. Cohort 5a (8 healthy subjects - 4 non-elderly adults and 4 elderly adults). Per randomization, there will be 6 active and 2 placebo subjects in each cohort: • Cohort 5a: 200% of 450 mg lithium carbonate equivalent of AL001 (6300 mg AL001 daily × 14 days - lithium dose equivalent to that used for bipolar/affective disorders, given as 10 × 210 mg AL001 capsules TID)

Drug: AL001; Other: Placebo

Multiple Ascending Doses of AL001 vs. Placebo - Cohorts 2b

EXPERIMENTAL

The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated. Cohort 2b (8 AD subjects). Per randomization, there will be 6 active and 2 placebo subjects in each cohort: • Cohort 2b: 100% 450 mg lithium carbonate equivalent of AL001 (3150 mg AL001 daily × 14 days, given as 5 × 210 mg AL001 capsules TID).

Drug: AL001; Other: Placebo

Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3b

EXPERIMENTAL

The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated. Cohort 3b (8 AD subjects). Per randomization, there will be 6 active and 2 placebo subjects in each cohort: • Cohort 3b: 140% of 450 mg lithium carbonate equivalent of AL001 (4410 mg AL001 daily × 14 days, given as 7 × 210 mg AL001 capsules TID)

Drug: AL001; Other: Placebo

Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4b

EXPERIMENTAL

The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated. Cohort 4b (8 AD subjects). Per randomization, there will be 6 active and 2 placebo subjects in each cohort: • Cohort 4b: 160% of 450 mg lithium carbonate equivalent of AL001 (5040 mg AL001 daily × 14 days, given as 8 × 210 mg AL001 capsules TID)

Drug: AL001; Other: Placebo

Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5b

EXPERIMENTAL

The data from the previous cohort must be deemed safe before the next sequential cohort may be enrolled and dosing initiated. Cohort 5b (8 AD subjects). Per randomization, there will be 6 active and 2 placebo subjects in each cohort: • Cohort 5b: 200% of 450 mg lithium carbonate equivalent of AL001 (6300 mg AL001 daily × 14 days - lithium dose equivalent to that used for bipolar/affective disorders, given as 10 × 210 mg AL001 capsules TID).

Drug: AL001; Other: Placebo

Interventions

AL001 DRUG

a crystal engineered lithium-salicylate-proline lithium delivery product

Also known as: Alzamend AL001

Multiple Ascending Doses of AL001 vs. Placebo - Cohort 1; Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3a; Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3b; Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4a; Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4b; Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5a; Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5b; Multiple Ascending Doses of AL001 vs. Placebo - Cohorts 2a; Multiple Ascending Doses of AL001 vs. Placebo - Cohorts 2b

Placebo OTHER

matching placebo formulation

Multiple Ascending Doses of AL001 vs. Placebo - Cohort 1; Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3a; Multiple Ascending Doses of AL001 vs. Placebo - Cohort 3b; Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4a; Multiple Ascending Doses of AL001 vs. Placebo - Cohort 4b; Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5a; Multiple Ascending Doses of AL001 vs. Placebo - Cohort 5b; Multiple Ascending Doses of AL001 vs. Placebo - Cohorts 2a; Multiple Ascending Doses of AL001 vs. Placebo - Cohorts 2b

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Mild to moderate Alzheimer's disease (reasonably good physical health per Investigator's review of medical \& surgical history, physical examination incl. neurological examination, 12-lead ECG, vital signs, and clinical laboratory tests)
• Able to understand and provide written informed consent and able to understand and follow instructions during study as determined by Investigator
• Subject and caregiver (if accompanying subject on site) willing to follow study procedures, willing \& able to adhere to study restrictions and to be confined at the clinical research center for 16 days
• Fluent in English speaking, reading, and writing (for cognitive testing)
• Availability of medical history to provide information about the cognitive and functional level of the participant and of a qualified source such as the caregiver willing and able to provide information about the cognitive and functional level of the participant
• Males (non-vasectomized and vasectomized) must agree to use barrier contraception during the study until after Study Day 42
• Females must meet criteria if childbearing for contraception or be non-childbearing
• Clinical diagnosis of dementia (neurocognitive disorder) by a qualified clinician based on the DSM-V criteria
• Considered AD Stage 2, 3, or 4 based on the FDA classification
• Mini-Mental State Examination (MMSE) score between 16 and 26, inclusive, at Screening
• Negative result to COVID-19 test at Screening and admission (performed on Day -1)

You may not qualify if:

• Clinically significant abnormalities (as determined by investigator based on medical history, physical examination, vital sign measurements, ECG findings, or clinical laboratory findings) that may affect subject safety or successful study participation
• Presence or history of any disorder that may prevent the successful completion of the study
• Other severe acute, chronic, or historical medical or psychiatric condition or laboratory abnormality or social circumstance that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in judgment of the Investigator, would make the subject inappropriate for entry into this study
• Evidence of clinically significant hematological, renal, endocrine, pulmonary, cardiovascular, dermatologic, muscular, or allergic disease or disorder (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) that may affect the safety or successful participant of the subject
• Any history or presence of gastrointestinal disease including chronic gastritis, hemorrhagic gastritis, peptic ulcers, duodenitis, diarrhea, or inflammatory bowel disease
• Any presence or history of acute or chronic liver diseases
• Any post-surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the study treatment
• Any history of frequent headache or migraine
• Kidney disease (eGFR \<60 mL/minute/1.73 m2)
• Uncontrolled tachy/brady arrhythmias, atrial fibrillation, or coronary heart failure
• Psychiatric or neurological illnesses (other than Alzheimer's disease), e.g., schizophrenia or other psychotic syndromes, Parkinson's disease and related movement disorders, myasthenia gravis, and seizure disorder/history of seizure disorder and/or severe head trauma (other than a single childhood febrile seizure)
• Presence of depression, except for mild depression with no acute episodes and stable condition, as determined by the Investigator
• History of untreated thyroid dysfunction that may be independently associated with cognitive impairment
• any medical condition that (per investigator's judgement) would affect subject safety and scientific integrity of the study, e.g., untreated hypothyroidism (TSH \>10 mIU/L) or vitamin B12 deficiency (\<300 pg/mL) which may contribute to cognitive impairment, delirium, non-AD dementia and other encephalopathies
• Hachinski scale score \>4 or evidence of stroke within the past 5 years

Sponsors & Collaborators

• Alzamend Neuro, Inc.: lead

Study Sites (2)

CenExel iResearch, LLC

Decatur, Georgia, 30030, United States

Location

Altasciences

Mount Royal, Quebec, H3P 3P1, Canada

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Eve Del Rio, MD, PhD
• Organization: Alzamend Inc.

Eve@RioPharma.com

9736993847

Study Officials

• Eric Sicard, MD

  Alzamend

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multi-center, placebo-controlled, double-blind, randomized, multiple ascending dose clinical trial to determine the safety and maximum tolerated dose of AL001.

Study Record Dates

• First Submitted: April 27, 2022
• First Posted: May 5, 2022
• Study Start: May 4, 2022
• Primary Completion: April 14, 2023
• Study Completion: May 15, 2023
• Last Updated: May 14, 2025
• Results First Posted: May 14, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); CA (1)