First in Human Study for Safety and Tolerability of AL003.

Healthy Clinical Trial

Official title:

A Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Single and Multiple Doses of AL003 in Healthy Participants and in Participants With Mild to Moderate Alzheimer's Disease.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03822208
• Other study ID #: AL003-1
• Status: Completed
• Phase: Phase 1
• Start date: March 29, 2019
• Est. completion date: May 6, 2021

Study information

• Verified date: September 2021
• Source: Alector Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The study will be conducted in 2 phases:

In the single ascending dose (SAD) phase, up to approximately 42 healthy adult participants will be sequentially enrolled into up to approximately 7 cohorts. In the multiple-dose (MD) phase, approximately 12 patients with mild to moderate Alzheimer's disease will be enrolled in one cohort.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: May 6, 2021
• Est. primary completion date: May 6, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Total body weight between 50 and 120 kg, inclusive

2. 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.

3. 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.

4. Females must be non-pregnant and non-lactating, and either surgically sterile, using double barrier method or abstinence.

5. 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

1. Ages 50-85 years, inclusive.

2. The participant should be capable of completing assessments alone, per local guidelines.

3. 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.

4. Clinical diagnosis of probable Alzheimer's disease dementia based on National Institute on Aging Alzheimer's Association criteria.

Exclusion Criteria:

1. Pregnant or lactating, or intending to become pregnant within 16 weeks after last dose of study drug.

2. 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.

3. 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.

4. Surgery or hospitalization during the 4 weeks prior to screening.

5. Planned procedure or surgery during the study.

6. Systemically, clinically significantly immunocompromised patients, owing to continuing effects of immune suppressing medication.

7. Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.

8. Past history of seizures, with the exception of childhood febrile seizures.

Related Conditions & MeSH terms

• Alzheimer Disease
• Healthy

Intervention

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

Other:
• Saline Solution
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

Locations

Country	Name	City	State
Australia	Nucleus Network	Melbourne
United States	Brain Matters Research	Delray Beach	Florida
United States	Charter Research	Lady Lake	Florida
United States	Columbia University	New York	New York
United States	PPD Clinical Research Unit	Orlando	Florida
United States	Synexus AES	The Villages	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Alector Inc.

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Pharmacokinetics (PK) of AL003	Serum and CSF concentration of AL003 at specific time points	85 days
Secondary	Maximum concentration (Cmax) for AL003	Evaluate Cmax for serum and CSF concentration of AL003 at specified time points	85 days
Secondary	Area under the curve concentration (AUC) for AL003	Evaluate AUC for serum and CSF concentration of AL003 at specified time points	85 days