A Phase I Study for Safety and Tolerability of AL002.

• ClinicalTrials.gov Identifier: NCT03635047
• Recruitment Status: Completed
• First Posted: August 17, 2018
• Last Update Posted: December 9, 2020
• Sponsor: Alector Inc.
• Information provided by (Responsible Party): Alector Inc.

Study Description

Brief Summary:

This is a multi-centre, 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 AL002.

Condition or disease	Intervention/treatment	Phase
Healthy; Alzheimer Disease	Biological: AL002; Other: Saline Solution	Phase 1

Detailed Description:

The study will be conducted in 2 phases:

In the single ascending dose (SAD) phase up to approximately 56 healthy adult participants will be sequentially enrolled into up to approximately 9 cohorts In the multiple-dose (MD) phase, approximately 32 patients with mild to moderate Alzheimer's disease will be enrolled in three cohorts.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 69 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Single and Multiple Doses of AL002 in Healthy Participants and in Participants With Mild to Moderate Alzheimer's Disease
• Actual Study Start Date: November 12, 2018
• Actual Primary Completion Date: August 3, 2020
• Actual Study Completion Date: November 25, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: AL002; AL002 by intravenous (IV) infusion	Biological: AL002; Single-doses of AL002 in up to 9 dose-escalating cohorts
Placebo Comparator: Saline Solution; placebo by intravenous (IV) infusion	Other: Saline Solution; Saline solution will be administered as a single infusion for each cohort in a ratio of 6 active and 2 placebo subjects for HV and 10 active and 2 placebo for patients

Outcome Measures

Primary Outcome Measures :

1. Evaluation of safety and tolerability of AL002 measured by number of subjects with adverse events and Dose Limiting Adverse Event (DLAEs) [ Time Frame: 141 days ]
   Incidence of adverse events and dose limiting Adverse Events during the DLAE observation period and/or study treatment periods.

Secondary Outcome Measures :

1. Pharmacokinetics (PK) of AL002 [ Time Frame: 85 days ]
   Serum and CSF concentration of AL002 at specified time points
2. Maximum plasma concentration (Cmax) for AL002 [ Time Frame: 85 days ]
   Evaluate Cmax for serum and CSF concentration of AL002 at specified time points
3. Area under the curve concentration (AUC) for AL002 [ Time Frame: 85 days ]
   Evaluate AUC for serum and CSF concentration of AL002 at specified time points

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Total body weight between 50 and 120 kg, inclusive.
2. Clinical laboratory evaluations (including chemistry panel fasted [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 (does not include alcohol) and at admission (testing 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
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.

Contacts and Locations

Locations

United States, Florida

Brain Matters Research

Delray Beach, Florida, United States, 33445

Compass Research - Orlando

Orlando, Florida, United States, 32806

Compass Research - The Villages

The Villages, Florida, United States, 32162

United States, New York

Columbia University

New York, New York, United States, 10032

Australia

Nucleus Network Pty Ltd

Melbourne, Australia

United Kingdom

University College London

London, United Kingdom

Sponsors and Collaborators

Alector Inc.

Investigators

• Study Director: Robert Paul, MD; Alector Inc.

More Information

• Responsible Party: Alector Inc.
• ClinicalTrials.gov Identifier: NCT03635047
• Other Study ID Numbers: AL002-1
• First Posted: August 17, 2018
• Last Update Posted: December 9, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

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