A Clinical Trial to evaluate AL002 in Participants with early Alzheimer's Disease
- Conditions
- Early Alzheimer’s DiseaseMedDRA version: 20.0Level: SOCClassification code 10029205Term: Nervous system disordersSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2019-001476-11-FR
- Lead Sponsor
- Alector Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 265
1.Participant must be in the Alzheimer’s continuum as defined by the 2018 NIA-AA Research Framework; this requires evidence of cerebral amyloidosis (A+) as detailed in the following:a.Must be positive by the APTUS™-Aß blood test prior to proceeding with either the amyloid-PET or CSF studies for confirmation of amyloid beta (Aß) pathology. Demonstration of amyloid pathology by amyloid-PET or CSF phosphorylated tau (pTau)/ amyloid beta (1-42) (Aß42) ratio is required. Participants with a positive historical amyloid-PET scan that has been collected =24 months prior to the start of screening and that meets the acceptable criteria for a historical amyloid-PET scan as outlined in Inclusion Criteria 1b will not be tested by APTUS™-Aß. Participants with a validated positive historical amyloid-PET scans are considered positive for cerebral Aß pathology without further testing. b.Has evidence of the AD amyloid pathology, as demonstrated either by positive amyloid-PET scan or by a CSF pTau/Aß42 ratio > 0.024 as measured by the Roche Elecsys assay. Historical amyloid-PET may be allowed to fulfil this criterion; historical CSF measurements will not be allowed to fulfil this criterion.2.Participants must demonstrate a clinical severity consistent with Stages 2, 3 or early 4 as defined in the 2018 NIA-AA Research Framework, also described as mild cognitive impairment and mild dementia. Further, participants must meet the following inclusion criteria to define clinical severity: a.Has mild symptomatology as defined by a screening MMSE score of =22 points. b.Has a Clinical Dementia Rating – Global Score of 0.5 to 1.0. c.Has evidence of episodic memory impairment as defined by a RBANS score on the Delayed Memory Index =85.3.If Participant is receiving symptomatic AD medications, the dosing regimen must have been stable for 3 months prior to screening.4.Participant is willing and able to give informed consent. If the study participant is not competent, a legally authorized representative must provide informed consent on their behalf, and participant must provide assent.5.Participant can be male or female, and is 50 to 85 years of age, inclusive.6.Participant weighs between 45 to 120 kg, inclusive.7. At screening, female participants must be nonpregnant and nonlactating, and 1 of the following conditions must apply: a.Participant is not a woman of childbearing potential (WOCBP) (either surgically sterilized, or physiologically incapable of becoming pregnant, or at least 1-year postmenopausal.b.Participant is a WOCBP and agrees to use an acceptable contraceptive method from screening until 8 weeks after the last dose of study treatment. Acceptable contraception is defined as using hormonal contraceptives or an intrauterine device combined with at least 1 of the following forms of contraception: a diaphragm or cervical cap, or a condom, or the sole sexual partner to a vasectomized male. Vasectomized males must have received medical assessment of surgical success. In addition, total abstinence, in accordance with the lifestyle of Participant, is acceptable. c.WOCBP must have a serum pregnancy test conducted at screening.8.Male participants must agree to use acceptable contraception and not donate sperm from screening until 8 weeks after the last dose of study treatment. Acceptable contraception for the male participant when having sexual intercourse with a WOCBP who is not currently pregnant is defined as using a condom. In addition, WOCBP partners must us
1.Participant has any evidence of a condition other than AD that may affect cognition2.Participant has history or presence of vascular disease that has the potential to affect cognitive function, or stroke within past 2 years, or ischemic attack within last 6 months3.Participant has history of severe, clinically significant CNS trauma, or history or presence of intracranial tumor, or presence of infections that affect brain function or history of infections with neurologic sequelae4.Participant has history or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits, or uveitis with medical intervention, chronic inflammatory or degenerative condition of the eye, current eye infection, any ongoing eye disorder requiring injectable medical therapy or planned invasive eye procedure during the study5.Participant has history of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder, or is at risk of suicide in the PI´s opinion6.Participant has history of alcohol and/or substance use disorder within the past 2 years7.Participant has MRI evidence of a. >2 lacunar infarcts. b. Any territorial infarct >1 cm3. c. White matter hyperintense lesions on the FLAIR sequence as per protocol 8.Participant has presence on MRI of microbleeds>5 and/or areas of leptomeningeal hemosiderosis as per protocol9.Participant has presence of significant cerebral vascular pathology, or any cortical stroke regardless of age as assessed by the MRI central reader10.Participant is unable to tolerate MRI procedures or has a contraindication11.Participant has uncontrolled hypertension or has a history or presence of an abnormal ECG12.Participant has history of ventricular dysrhythmias or risk factors for ventricular dysrhythmias13.Participant has significant kidney disease as per protocol14.Participant has impaired hepatic function as per protocol15.Participant is positive for hepatitis B surface Ag, total hepatitis B core antibody, HIV-1 or -2 antibodies or antigen, or history of spirochetal infection of the CNS. Participants with a positive hepatitis C virus antibody will be allowed if hepatitis C RNA is negative16.Participants with active or latent TB disease should not be enrolled in the trial17. Any chronic active immune disorder requiring systemic immunosuppressive therapy within 1 year prior to study enrollment18.Participant has abnormal screening thyroid function tests19.Participant has screening folic acid or low vitamin B12 levels that may be contributing to cognitive impairment20.Participant has screening hemoglobin A1c >8% or poorly controlled insulin dependent diabetes21.Participant has deformity of the lumbosacral region of the spine that in the PI´s opinion would contraindicate LP in those who can only be CSF eligible due to regional lack of availability of PET ligands, or in those who are in Part 122.Participant has clinically significantly abnormal screening blood or urine results that remain abnormal, or has impaired coagulation23.Participant has history of cancer except: a. Is clinically cured. Is not being actively treated and is not likely to require treatment in next 3 years. c. Low probability of recurrence d. Prostate cancer, without progression in the past 2 years24.Participant has known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins25.Participant with othe
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method