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
Sponsors
Alector, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The participant has completed the Planned Treatment Period in the AL002-2 study. Completion of the Planned Treatment Period is defined as any participant who did not prematurely and permanently discontinue IMP in the AL002-2 study. 2. The participant is willing and able to give informed consent. Where local regulations permit inclusion of participants deemed not able to provide informed consent, a legally authorized representative must provide informed consent on his or her behalf, and the participant must provide assent, in accordance with the local regulations, guidelines, and institutional review board or independent ethics committee. 3. The participant has availability of a person (“study partner”) who, in the Investigator’s opinion, has frequent and sufficient contact with the participant (eg, at least 10 hours per week of in person contact), 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. a. The study partner must have sufficient cognitive capacity, in the Investigator’s opinion, to accurately report upon the participant’s behavior, cognitive, and functional abilities. The study partner should be in sufficiently good general health, in the Investigator’s opinion, to have a high likelihood of maintaining the same level of interaction with the participant and participation in study procedures throughout the study duration. b. Every effort should be made to have the same study partner participate throughout the duration of the study, and to have the same study partner as in the parent study. 4. The participant and study partner are fluent in the language of the tests used at the study site as assessed by site personnel. 5. The participant is willing and able to complete all aspects of the study (including MRI, optional LP, genotyping, and optional PET imaging, as applicable). The participant should be capable of completing assessments either alone or with the help of the study partner. 6. The participant has adequate visual and auditory acuity, in the Investigator’s opinion, sufficient to perform the neuropsychological testing (corrective lenses and hearing aids are permitted). 7. Participant agrees not to donate blood or blood products for transfusion for the duration of the study and for 1 year after the final dose of study drug. Inclusion criteria for participants in the optional tau PET imaging assessment with [18F]MK-6240 only: 8. Participant has not had excessive radiation exposure prior to enrollment in the trial, as defined by local standards. 9. [18F]MK-6240 is available to the PET imaging center based on manufacturing distribution network and local regulations. Inclusion criteria for participants in the optional longitudinal amyloid PET imaging assessment only: 10. Participant has not had excessive radiation exposure prior to enrollment in the trial, as defined by local standards. 11. An approved amyloid radiotracer is available to the PET imaging center based on manufacturing distribution network and local regulations. Inclusion criteria for participants in the optional at-home and/or in-clinic WLSA only: 12. For at-home participation: a. Participant has an available and willing study partner to administer the WLSA. b. Participant has WiFi access in their residence or WiFi access in a private area where the testing can take pla
Exclusion criteria
Exclusion criteria: Participants deemed not able to provide consent or assent by the Investigator or by local regulations. 2. Participants who were prematurely and permanently discontinued from treatment in the parent study for safety reasons. 3. The participant has MRI evidence of: a. >2 lacunar infarcts. b. Any territorial infarct >1 cm3. c. White matter hyperintense lesions on the FLAIR sequence that correspond to an overall Fazekas score of 3. d. Participants who have an increase in their number of microbleeds, since the previous screening/ baseline MRI in the AL002-2 study and >5, should be discussed with the Medical Monitor. e. Participants who have developed ARIA-E and ARIA-H in the parent study and who were permitted to continue dosing according to the ARIA management guidelines, will not be excluded from participation in the AL002-LTE, on the basis of microbleeds or hemosiderosis. 4. Participation in the AL002-LTE is deemed inappropriate for any reason per Investigator discretion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the long-term safety and tolerability of IMP (AL002) in participants with AD. To evaluate the effect of immunogenicity to IMP on safety, PK, and PD biomarkers in participants with AD.;Secondary Objective: To evaluate the effects of IMP in participants with AD on exploratory clinical outcome assessments (COAs) and PD biomarkers.;Primary end point(s): • Incidences of AEs, including AESIs and SAEs • Vital signs, clinical laboratory results, and incidence of findings from physical, neurological, ophthalmological exams, and ECG • C-SSRS • MRI abnormalities • Assess the effect of dose titration on ARIA;Timepoint(s) of evaluation of this end point: Incidences of AEs, including AESIs and SAEs during the study, from the time a participant signs ICF until EOS. • Vital signs every visit, clinical Lab results at screening week 1,13 29, 41, and EOA/ET, and incidence of findings from physical observed or reported during the study , neurological and ophthalmological exams at screening Week9, 17, 25,33,41,49 and EOS/ST & ECG at screening, week 1,5,9,13,25,49, and EOS/ET • C-SSRS_ every visit • MRI abnormalities_ Screening, week 9, 17,25,33,41, and EOS/ET • Assess the effect of dose titration on ARIA_ For all post-screening MRIs, the MRI should occur at least 5 days prior to the next dose administration and no more than 10 days prior to the next dose administration, with results received from the central imaging vendor prior to dosing | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •CDR-SB • MMSE • RBANS-Update • ADAS-Cog13 • ADCS-ADL-MCI • ADCOMS • Levels of sTREM2 in CSF and/or plasma • Levels of biomarkers related to microglia function in CSF and/or plasma (eg, CSF1R, IL1RN, osteopontin, YKL-40) • Levels of biomarkers related to AD pathology in CSF and/or plasma (eg, Aß40, Aß42, pTau, tTau) • Levels of neurodegeneration biomarkers in plasma and/or CSF (eg, NfL) • Brain volume, assessed by volumetric MRI • Brain pathological tau burden as assessed by longitudinal tau PET for participants who agree to participate in the optional assessment only •Brain amyloid burden as assessed by longitudinal amyloid PET scanning for participants who agree to participate in the optional assessment only Speech measurements via the WLSA for participants who agree to participate in this optional assessment only;Timepoint(s) of evaluation of this end point: CDR-SB, MMSE, RBANS-Update,ADAS-Cog13, ADCS-ADL-MCI , ADCOMS at screening, week 25, & EOT/ES Levels of sTREM2 in CSF and/or plasma, Levels of biomarkers related to microglia function in CSF and/or plasma, Levels of biomarkers related to AD pathology in CSF and/or plasma ,Levels of neurodegeneration biomarkers in plasma and/or CSF ,at the point described on the protocol and scheduled of events • Brain volume, assessed by volumetric MRI • Brain pathological tau burden as assessed by longitudinal tau PET for participants who agree to participate in the optional assessment only at screening & EOS/ET •Brain amyloid burden as assessed by longitudinal amyloid PET scanning for participants who agree to participate in the optional assessment only Speech measurements at screening & EOS/ET | — |
Countries
Argentina, Australia, Canada, France, Germany, Italy, Netherlands, Poland, Spain, United Kingdom, United States
Contacts
Public ContactMedical Doctor
Alector Inc.
Outcome results
None listed