First in Human Study for Safety and Tolerability of AL003.

NCT03822208 | Completed Phase 1 FDA Drug

• 1 other identifier: AL003-1
• Study Type: interventional
• Target: 54
• Locations: 2 countries
• Sites: 6

Brief Summary

This is a multi-center, randomized, double-blind, placebo-controlled, dose escalation first in human (FIH) study in healthy adults and in patients with mild to moderate Alzheimer's disease. The study is designed to systematically assess the safety (including immunogenicity) and tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AL003.

Conditions

Healthy; Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• Evaluation of safety and tolerability of AL003 measured by number of subjects with adverse events and dose limiting adverse events (DLAE)

  Incidence of adverse events during the treatment and follow up periods through out the study.

  141 days

Secondary Outcomes (3)

• Pharmacokinetics (PK) of AL003

  85 days

• Maximum concentration (Cmax) for AL003

  85 days

• Area under the curve concentration (AUC) for AL003

  85 days

Study Arms (2)

AL003 by intravenous (IV) infusion

ACTIVE COMPARATOR

Single-doses of AL003 in dose-escalating cohorts Multiple doses of AL003 in single cohort

Biological: AL003

Placebo by intravenous (IV) infusion

PLACEBO COMPARATOR

Matching saline solution will be administered for placebo subjects

Other: Saline Solution

Interventions

AL003 BIOLOGICAL

Single-doses of AL003 in dose-escalating cohorts Multiple doses of AL003 in a single cohort

AL003 by intravenous (IV) infusion

Saline Solution OTHER

Saline Solution will be administered as a single infusion for each dose escalation cohort in a ratio of 6 active and 2 placebo and as multiple infusions in the single cohort in a ratio of 10 active and 2 placebo

Placebo by intravenous (IV) infusion

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Total body weight between 50 and 120 kg, inclusive
• Clinical laboratory evaluations (including chemistry panel fasted \[at least 8 hours\], complete blood count (CBC), and urine analysis) within the reference range for the test laboratory, unless deemed not clinically significant by the Investigator. A count of the segmented neutrophils and bands should be performed when results from the white blood cells (WBCs) are not within the reference range.
• Negative test for selected drugs of abuse at screening (dose not include alcohol) and at admission (does include alcohol breath test). A positive result may be verified by re-testing (up to one false positive result permitted) and may be followed up at the discretion of the Investigator.
• Females must be non-pregnant and non-lactating, and either surgically sterile, using double barrier method or abstinence.
• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), laboratory tests, and vital signs.
• For MD cohort
• Ages 50-85 years, inclusive.
• The participant should be capable of completing assessments alone, per local guidelines.
• Availability of a person ("study partner") who, in the Investigator's judgment, has frequent and sufficient contact with the participant and is able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to provide information at clinic visits, which require partner input for scale completion, and signs the necessary consent form, per local guidelines.
• Clinical diagnosis of probable Alzheimer's disease dementia based on National Institute on Aging Alzheimer's Association criteria.

You may not qualify if:

• Pregnant or lactating, or intending to become pregnant within 16 weeks after last dose of study drug.
• Participation in a clinical trial within 30 days before randomization; use of any experimental oral therapy within 30 days or 5 half-lives prior to Day 1, whichever is greater; or use of any biologic therapy within 12 weeks or 5 half-lives prior to Day 1, whichever is greater. Participants who have received an experimental therapy that has no half-life, like a vaccine, should have completed that therapy at least 12 weeks prior to Day 1. Participants who have received an experimental vaccine against a central nervous system (CNS) target, such as beta-amyloid or tau, are not eligible for this study.
• Any non-experimental vaccine within 2 weeks of randomization, until 2 weeks after the last dose. It is advised that prospective participants receive their annual influenza vaccine as early as possible in advance of the flu season, and then wait 2 weeks prior to randomization. It is permitted to receive the annual influenza vaccine during the screening period.
• Surgery or hospitalization during the 4 weeks prior to screening.
• Planned procedure or surgery during the study.
• Systemically, clinically significantly immunocompromised patients, owing to continuing effects of immune suppressing medication.
• Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.
• Past history of seizures, with the exception of childhood febrile seizures.

Sponsors & Collaborators

• Alector Inc.: lead

Study Sites (6)

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

Charter Research

Lady Lake, Florida, 32159, United States

Location

PPD Clinical Research Unit

Orlando, Florida, 32806, United States

Location

Synexus AES

The Villages, Florida, 32162, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Nucleus Network

Melbourne, Australia

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Robert Paul, MD

  Alector Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: January 30, 2019
• Study Start: March 29, 2019
• Primary Completion: May 6, 2021
• Study Completion: May 6, 2021
• Last Updated: September 17, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share

Locations

AU (1); US (5)