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.
Latest Information Update: 27 May 2022
At a glance
- Drugs AL 003 (Primary)
- Indications Alzheimer's disease
- Focus Adverse reactions; First in man
- Sponsors Alector
- 26 Apr 2022 Results assessing safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AL003 in healthy volunteers (HV) and patients with mild to moderate AD presented at the 74th Annual Meeting of the American Academy of Neurology 2022
- 15 Sep 2021 Status changed from active, no longer recruiting to completed.
- 13 Jan 2021 Status changed from recruiting to active, no longer recruiting.
Most Recent Events
Trial Overview
Purpose
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.
Primary Endpoints
Evaluation of safety and tolerability of AL003 measured by number of subjects with adverse events and dose limiting adverse events (DLAE)
description: Incidence of adverse events during the treatment and follow up periods through out the study.
time_frame: 141 days
Other Endpoints
Pharmacokinetics (PK) of AL003
description: Serum and CSF concentration of AL003 at specific time points
time_frame: 85 days
Maximum concentration (Cmax) for AL003
description: Evaluate Cmax for serum and CSF concentration of AL003 at specified time points
time_frame: 85 days
Area under the curve concentration (AUC) for AL003
description: Evaluate AUC for serum and CSF concentration of AL003 at specified time points
time_frame: 85 days [1]
Diseases Treated
Indication | Qualifiers | Patient Segments |
---|---|---|
Alzheimer's disease | treatment | mild, moderate |
Biomarker
NCT Number | Biomarker Name | Biomarker Function |
---|---|---|
NCT03822208 | Granulocyte-macrophage colony-stimulating factor (GM-CSF) | Outcome Measure |
Subjects
- Subject Type patients & volunteers
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Number
Planned: 54
Actual: 54
- Sex male & female
- Age Group 18-85 years; adult; elderly
Patient 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.
Patient 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.
Trial Details
Identifiers
Identifier | Owner |
---|---|
NCT03822208 | ClinicalTrials.gov: US National Institutes of Health |
AL003-1 | - |
Organisations
- Sponsors Alector
- Affiliations Alector
Trial Dates
-
Initiation Dates
Planned : 01 Mar 2019
Actual : 29 Mar 2019
-
Primary Completion Dates
Planned : 01 May 2021
Actual : 06 May 2021
-
End Dates
Planned : 01 Aug 2021
Actual : 06 May 2021
Other Details
- Design double-blind; multicentre; parallel; prospective; randomised
- Phase of Trial Phase I
- Location Australia; USA
- Focus Adverse reactions; First in man
Interventions
Drugs | Route | Formulation |
---|---|---|
AL 003Primary Drug | Intravenous | Infusion |
AL003 by intravenous (IV) infusion
Single-doses of AL003 in dose-escalating cohorts Multiple doses of AL003 in single cohort Biological: AL003 (Single-doses of AL003 in dose-escalating cohorts Multiple doses of AL003 in a single cohort)
Placebo by intravenous (IV) infusion
Matching saline solution will be administered for placebo subjects 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)
Results
Adverse events
Treatment with IV AL 003 was safe and generally well tolerated, in healthy volunteers and in patients (n=54) with mild to moderate Alzheimer's disease, in a phase I trial. The most frequently reported adverse events were headache (20.7%), post-lumbar puncture syndrome (i.e., headache after lumbar puncture; 17.2%), nausea (13.8%), upper respiratory tract infection (13.8%), and puncture site pain (10.3%). Dose levels up to 15 mg/kg were well tolerated in HVs with immune-related adverse events at higher dose levels [2] .
Publications
-
Maslyar D, Paul R, Long H, Rhinn H, Tassi I, Morrison G, et al. A Phase 1 Study of AL003 in Healthy Volunteers and Participants with Alzheimer?s disease. AAN-2022 2022; abstr. P5.002.
Available from: URL: https://index.mirasmart.com/aan2022/PDFfiles/AAN2022-003582.html
Trial Centres
Investigators
Investigator | Centre Name | Trial Centre Country |
---|---|---|
Study Coordinator | Brain Matters Research, Charter Research, Columbia University, PPD Clinical Research Unit, Synexus AES | USA |
Study Lead
650-410-3155 info@alector.com
show details
|
Alector Inc. |
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Centres
Centre Name | Location | Trial Centre Country |
---|---|---|
Alector Inc. |
-
|
-
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Brain Matters Research | Delray Beach, Florida | USA |
Charter Research | Lady Lake, Florida | USA |
Columbia University | New York, New York | USA |
Nucleus Network | Melbourne | Australia |
PPD Clinical Research Unit | Orlando, Florida | USA |
Synexus AES | The Villages, Florida | USA |
Trial History
Event Date | Event Type | Comment |
---|---|---|
26 Apr 2022 | Results | Results assessing safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AL003 in healthy volunteers (HV) and patients with mild to moderate AD presented at the 74th Annual Meeting of the American Academy of Neurology 2022 Updated 27 May 2022 |
20 Sep 2021 | Other trial event | Last checked against ClinicalTrials.gov record. Updated 20 Sep 2021 |
15 Sep 2021 | Status change - completed | Status changed from active, no longer recruiting to completed. Updated 20 Sep 2021 |
15 Jan 2021 | Biomarker Update | Biomarkers information updated Updated 17 Sep 2021 |
13 Jan 2021 | Status change - active, no longer recruiting | Status changed from recruiting to active, no longer recruiting. Updated 18 Jan 2021 |
16 Nov 2020 | Completion date | Planned End Date changed from 1 Feb 2021 to 1 Aug 2021. Updated 23 Nov 2020 |
16 Nov 2020 | Other trial event | Planned primary completion date changed from 1 Dec 2020 to 1 May 2021. Updated 23 Nov 2020 |
23 Jul 2020 | Protocol amendment | Time frame changed from 134 days to 141 days for safety and tolerability endpoint. Updated 28 Jul 2020 |
23 Jul 2020 | Completion date | Planned End Date changed from 1 Jul 2020 to 1 Feb 2021. Updated 28 Jul 2020 |
23 Jul 2020 | Other trial event | Planned primary completion date changed from 1 Apr 2020 to 1 Dec 2020. Updated 28 Jul 2020 |
18 Apr 2019 | Status change - recruiting | Status changed from not yet recruiting to recruiting. Updated 22 Apr 2019 |
01 Feb 2019 | New trial record | New trial record Updated 01 Feb 2019 |
Table of Contents
References
-
ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.
Available from: URL: http://clinicaltrials.gov -
Maslyar D, Paul R, Long H, Rhinn H, Tassi I, Morrison G, et al. A Phase 1 Study of AL003 in Healthy Volunteers and Participants with Alzheimer?s disease. AAN-2022 2022; abstr. P5.002.
Available from: URL: https://index.mirasmart.com/aan2022/PDFfiles/AAN2022-003582.html
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