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.
- Conditions
- Alzheimers Disease - Neurodegenerative disease - Dementia10012303
- Registration Number
- NL-OMON50153
- Lead Sponsor
- Alector Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
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
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 mm Hg or supine diastolic blood pressure > 90 or
<50 mm Hg at screening or admission. Duplicate assessments will be performed
and the average of the 2 assessments of BP will be used to exclude a
participant.
b. For MD participants with AD, sustained diastolic blood pressure >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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method