Early Alzheimer’s Disease MedDRA version: 20.0 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: AL002
Product Code: AL002
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: AL002
Other descriptive name: Recombinant anti-human (
Sponsors
Alector Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Participant must be in the AD continuum as defined by the 2018 NIA-AA Research Framework; this requires evidence of cerebral amyloidosis (A+) as detailed:a.Must be positive by the PrecivityADAß blood test prior to proceeding with either the amyloid-PET or CSF assements for confirmation of amyloid pathology. Confirmation of amyloid pathology b is described in criterion 1b below. Participants with a low APS are not eligible for study participation. Prospective participants who are considered to be amyloid positive via either historical amyloid-PET scan or CSF test may forego the initial screen with the PrecivityAD Aß. b.Confirmation of amyloid pathology as demonstrated either by positive amyloid-PET scan or by a CSF pTau/Aß42 ratio > 0.024 as measured bythe Elecsys assay. c.Participants who do not have confirmation of amyloid pathology based on an initial Amyloid PET scan may opt to have a second assessment with CSF. Participants who do not have confirmation of amyloid pathology on an initial CSF pTau/Aß42 measurement may opt to have a second assessment with an Amyloid PET scan2. 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 =20 points. b.Has a (CDR-GS) – 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 or =95 as described in the protocol .3.If Participant is receiving symptomatic AD medications, the dosing regimen must have been stable for 60days prior to screening not expected to change during study, and must not be initiated, modified, or stopped within 90 days prior to screening start.4.Participant is willing and able to give informed consent. Where not permitted by local regulations, participants deemed not able to provide consent by the PI will not be enrolled, where local regulation permit it, 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 age inclusive.6.Participant =120 kg.7. At screening, female participants must be nonpregnant and nonlactating, and 1 of the following conditions must apply: a.Participant is not a WOCBP (either surgically sterilized, or physiologically incapable of becoming pregnant, or at least 1y postmenopausal.b.Participant is a WOCBP and agrees to use an acceptable contraceptive method from screening until12 weeks after the last dose of study drug. Acceptable contraception is defined on the protocol. 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 12 weeks after the last dose of study drug. 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 use hormonal contraceptives or an intrauterine device. Vasectomized male participants should have received medical assessment of surgical success.9. Participant has availability of a person ("study partner") who, in the PI´s opinion, has frequent and sufficient contact with Participant, is able to p
Exclusion criteria
Exclusion criteria: 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 2y,transient ischemic attack within last 180d before screening, or presence on MRI of any cortical stroke regardless age3.Participant has history of cerebrovascular accident, severe clinically significant CNS trauma, history or presence of intracranial tumor, infections that affect brain function, or history of infections with neurologic sequelae4. Participant currently has or has had an acute illness that requires or required IV antibiotics within 30d prior to first study drug admin.5Participant has history or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits, or any ongoing eye disorder per protocol 6.Participant has any history of schizophrenia, schizoaffective disorder, major depression, bipolar disorder, or is at risk of suicide in PI´s opinion7.Participant has history of alcohol and/or moderate to severe substance use disorder in the past 2y 8.Participant has MRI evidence of a. >2 lacunar infarcts. b. Territorial infarct >1 cm3. c. White matter hyperintense lesions on the FLAIR sequence per protocol 9.Participant has presence on MRI of microbleeds>5 and/or areas of leptomeningeal hemosiderosis per protocol10.Participant has presence of significant cerebral vascular pathology, as assessed by the MRI central reader11.Participant is unable to tolerate MRI procedures or has a contraindication, those able to tolerate MRI with intermittent use of a low-dose benzodiazepine or anxiolytic may be included in the study.12. Uncontrolled hypertension as defined in the protocol or presence of an abnormal ECG.13.Participant has unstable ventricular dysrhythmias 14.Participant has significant kidney disease per protocol15.Participant has impaired hepatic function per protocol16.Participant is positive for hepatitis B surface Ag per protocol , or history of spirochetal infection. Participants with a positive HCV virus Ab will be allowed if HCV RNA is negative17.Participants with active or latent TB disease should not be enrolled 18. Any chronic active immune disorder requiring systemic immunosuppressive therapy within 1y prior to study enrollment19.Participant has abnormal screening TSH20.Participant has screening folic acid or low vitamin B12 levels that may be contributing to cognitive impairment21. Participant is positive for presence of APOE e4/e4 genotype.22.Participant has screening Hgb A1c >8% or poorly controlled diabetes23.Participant has contraindication for LP including deformity of the lumbosacral region of the spine that in the PI´s opinion would contraindicate LP for participants in Part 1 and Part 2 who can only be CSF eligible due to regional lack of availability of PET ligands, or consent to the optional LP assessments 24.Participant has clinically significantly abnormal screening blood or urine results that remain abnormal, or has impaired coagulation25.Participant has history of cancer with the exceptions per protocol: 26.Participant has known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins 27.Participant has had any surgery or hospitalization within 30d prior to first study drug admin 28.Participant with other severe or unstable medical c
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of AL002 in participants with Early AD in delaying disease progression compared to standard of care;Secondary Objective: To evaluate the efficacy of AL002 in participants with Early AD on efficacy as measured by the rate of change in COAs Pharmacokinetics: To estimate the concentration of AL002 in participants with Early AD in serum and CSF (when available) Safety: To evaluate the safety and tolerability of AL002 in participants with Early AD Exploratory: To evaluate the effects of AL002 in participants with Early AD on exploratory PD biomarkers;Primary end point(s): Disease progression as measured by change from baseline in the CDR-SB Primary Estimand for Primary Efficacy: Endpoint: The primary clinical question of interest is what is the potential relative treatment difference between AL002 and placebo, across all post-baseline timepoints in adult patients with Early AD while on study medication, regardless of other interventions. The estimand is described by the following attributes: Treatment condition: while on treatment (hypothetical strategy) regardless of other interventions (treatment policy strategy). Target population: adult patients with Early AD as defined as a percentage by the protocol inclusion/exclusion criteria. Primary endpoint: change from baseline in CDR-SB score to Weeks 24, 48, 72, and 96. Accounting for intercurrent events: a composite strategy will be used to handle intercurrent events as below: - hypothetical strategy for handling premature study drug discontinuation for any reason, - treatment policy strategy for handling all other intercurrent events. Population-level summary: the percent reduction of the relative to placebo group clinical decline (eg, increase in CDR-SB).the proportional treatment effect), comparing each dose level to placebo.;Timepoint(s) of evaluation of this end point: CDR will be done at screening, and on weeks 25, 49, 73, and 97. Also at early termination (ET) and FU (ever | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: • Change from baseline in MMSE • Change from baseline in RBANS - Update • Change from baseline in ADAS Cog13 • Change from baseline in ADCS-ADL-MCI • Change from baseline in ADCOMS Secondary Efficacy Estimands: The main estimand for the secondary efficacy objectives is defined with similar attributes as for the primary estimand except that it is endpoint specific. The treatment effect is defined as a percentage reduction of the placebo group clinical decline. Pharmacokinetic Endpoints: Serum PK concentrations of AL002 and relevant PK parameters CSF PK concentrations of AL002 (when available) Safety Endpoints: Incidences of AEs, including AESIs, and SAEs Changes from baseline in vital signs, physical findings, neurological findings, ophthalmological findings, ECG, and clinical laboratory results C-SSRS MRI abnormalities Exploratory PD Biomarker Endpoints: Changes from baseline in levels of sTREM2 in CSF and/or plasma Changes from baseline in levels of biomarkers related to microglia function in CSF and/or plasma (eg, CSF1R, IL1RN, osteopontin, YKL-40) Changes from baseline in levels of biomarkers related to AD pathology in CSF and/or plasma (eg, Aß40, Aß42, pTau, tTau) Changes from baseline in levels of neurodegeneration biomarkers in plasma and CSFa (eg, NfL) Changes from baseline in brain volume, assessed by volumetric MRI Changes from baseline in brain pathological tau burden as assessed by Tau-PET (for participants who agree to participate in the optional assessment only) Changes from baseline in brain amyloid burden as assessed by longitudinal Amyloid PET scanning (for participants who agree to participate in the optional assessment only) Changes from baseline in speech measurements via the WLSA (for participants who agree to participate in the optional assessment only);Timepoint(s) of evaluation of this end point: MMSE, RBANS, ADAS-Cog13,and ADCS-ADL-MCI tests performed at weeks 25,4 | — |
Countries
Argentina, Australia, Canada, France, Germany, Italy, Netherlands, Poland, Spain, United Kingdom, United States
Contacts
Public ContactMedical Doctor
Alector Inc.
Outcome results
None listed