First in Human Study for Safety and Tolerability of AL003.

Phase 1

Completed

• Conditions: Healthy; Alzheimer Disease
• Interventions: Other: Saline Solution; Biological: AL003

• Registration Number: NCT03822208
• Lead Sponsor: Alector Inc.

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2019-01-28
• Study First Submitted QC: 2019-01-28
• Study First Posted: 2019-01-30
• Study Start: 2019-03-29
• Primary Completion: 2021-05-06
• Study Completion: 2021-05-06
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-15
• Last Update Posted: 2021-09-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 54

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo by intravenous (IV) infusion	Saline Solution	Matching saline solution will be administered for placebo subjects
AL003 by intravenous (IV) infusion	AL003	Single-doses of AL003 in dose-escalating cohorts Multiple doses of AL003 in single cohort

Primary Outcome Measures

Name	Time	Method
Evaluation of safety and tolerability of AL003 measured by number of subjects with adverse events and dose limiting adverse events (DLAE)	141 days	Incidence of adverse events during the treatment and follow up periods through out the study.

Secondary Outcome Measures

Name	Time	Method
Maximum concentration (Cmax) for AL003	85 days	Evaluate Cmax for serum and CSF concentration of AL003 at specified time points
Pharmacokinetics (PK) of AL003	85 days	Serum and CSF concentration of AL003 at specific time points
Area under the curve concentration (AUC) for AL003	85 days	Evaluate AUC for serum and CSF concentration of AL003 at specified time points

Trial Locations

Locations (6)

Brain Matters Research; 🇺🇸 Delray Beach, Florida, United States

Synexus AES; 🇺🇸 The Villages, Florida, United States

PPD Clinical Research Unit; 🇺🇸 Orlando, Florida, United States

Charter Research; 🇺🇸 Lady Lake, Florida, United States

Nucleus Network; 🇦🇺 Melbourne, Australia

Columbia University; 🇺🇸 New York, New York, United States