Alzheimers Disease - Neurodegenerative disease - Dementia
Conditions
Interventions
Group L
In group L 12 participants will participate of which approximately 10
participants will receive the study drug and 2 participants placebo. Of the
first two participants in group L one will r
Sponsors
Alector Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion 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, 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 1 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 (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or use highly effective contraceptive method (oral contraceptives pills [OCPs], long acting implantable hormones, injectable hormones, a vaginal ring or an intrauterine device [IUD]) from screening until study completion, including the follow-up period for at least 16 weeks after the last dose of AL002, or be post-menopausal for *12 months. For healthy volunteers, post-menopausal status will be confirmed through testing of FSH levels (* 40 IU/mL) at screening; for participants with AD, post-menopausal status will be assessed through medical history with assessment of potential alternative causes of amenorrhea as clinically indicated). Females who are abstinent from heterosexual intercourse will also be eligible. 5. Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening and admission and be willing to have additional pregnancy tests as required throughout the study. 6. Males must be surgically sterile (>30 days since vasectomy with no viable sperm), abstinent, or if engaged in sexual relations with a WOCBP, the participant and his partner must be surgically sterile (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method from screening until study completion, including the follow-up period, for at least 16 weeks after the last dose of AL002. Acceptable methods of contraception include the use of condoms and the use of an effective contraceptive for the female partner (WOCBP) that includes: OCPs, long acting implantable hormones, injectable hormones, a vaginal ring or an IUD. Male participants whose female partner is post-menopausal, and participants who are abstinent from heterosexual intercourse will also be eligible. Male participants must agree to refrain from donating sperm from screening until study completion, including the follow-up period, for at least 16 weeks after the last dose of AL002. In addition, for the MD cohorts (i.e. participants with AD): 9. Ages 50-85 years, inclusive. 10. The participant should be capable of completing assessments either alone or with the help of the study partner (where appropriate), per local guidelines. 11. 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 inf
Exclusion criteria
Exclusion criteria: 1. Pregnant, 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 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. Blood transfusion within 8 weeks prior to screening. 7. Donation or loss of blood (excluding the volume of blood that will be drawn during screening procedures) as follows: 50-499 mL of blood within 30 days or > 499 mL of blood within 56 days prior to study drug administration. 8. Poor peripheral venous access. 9. History of major depression (within the past 5 years) unless effectively treated at enrollment and for the duration of the study, at the discretion of the Investigator. History of schizophrenia, schizoaffective disorder, or bipolar disorder. 10. Alcohol and/or substance abuse or dependence (according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) within the past 2 years. 11. Within the last 2 years, unstable or clinically significant cardiovascular disease (e.g. myocardial infarction, angina pectoris, New York Heart Association Class II or more cardiac failure). 12. Uncontrolled abnormal blood pressure a. For healthy volunteers, as indicated by sustained supine systolic blood pressure (BP) > 140 or 90 or 95 mm Hg performed either sitting or supine. No repeated measurements for eligibility are required for multidose participants. 13. Resting heart rate at screening of >100 or < 40 beats per minute. 14. Chronic kidney disease as indicated by a screening creatinine clearance < 30 mL/min as calculated by the central laboratory using the Cockcroft Gault formula, which remains < 30 mL/min if retested. 15. Impaired hepatic function as indicated by screening aspartate aminotransferase (AST) or alanine aminotransferase (ALT) * 2 or total bilirubin * 1.5 x the upper limit of normal, which remains above these limits if retested due to a slightly elevated initial result or abnormalities in synthetic function tests that are judged by the Investigator to be clinically significant. 16. Histo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The safety endpoints of this study are: * Incidence, nature, and severity of serious adverse event (SAE)s and adverse events of special interest (AESI) * Incidence of dose limiting adverse events (DLAE) * Incidence of treatment discontinuations due to AEs * Incidence of dose reductions due to AEs * Mean changes in clinical laboratory tests from baseline over time; incidence of treatment emergent abnormal laboratory values and abnormal laboratory values reported as AEs * Physical and neurologic examination abnormalities * Ophthalmological examination abnormalities * Mean change in vital signs from baseline over time and incidence of abnormal vital sign measurements * Suicidal ideation, suicidal behavior, and self-injurious behavior without suicidal intent, as determined using the Sheehan-STS (for the MD participant cohort only) * Incidence of ADAs during the study relative to the prevalence of ADAs at baseline (in SAD healthy adult participant cohorts and in MD participant cohort). AEs of special interest will be tracked and are defined as occurrences of: * ARIA-E, * ARIA-H, * An AE Grade 2 or higher of Uveitis. 6.2.2. Pharmacokinetic Endpoints Pharmacokinetic endpoints for the study are: * Serum concentration of AL002 at specified time points, * Relationship between serum concentration or PK parameters for AL002 and safety endpoints, Relationship between serum, CSF concentration, or PK parameters for AL002 and activity or PD endpoints (relationship with activity is an endpoint only for the MD participant cohort - i.e. participants with AD). 6.2.3. Exploratory Clinical Outcomes Exploratory clinical outcome endpoints (for the MD participant cohort only - i.e. participants with AD) are: * Clinical Dementia Rating Sum of Boxes (CDR-SB) score (change after dosing relative to baseline) * Mini-Mental State Examination (MMSE) score (change after dosing relative to baseline) * Repeatable Battery for the Assessment of Neuropsychological St | — |
Secondary
| Measure | Time frame |
|---|---|
| See above | — |
Countries
Netherlands
Outcome results
None listed