A MULTICENTER, LONG-TERM EXTENSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND EFFICACY OF AL002 IN PARTICIPANTS WITH ALZHEIMER*S DISEASE
- Conditions
- AlzheimerDementia10057167
- Registration Number
- NL-OMON53422
- Lead Sponsor
- Alector
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 4
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.
12. For at-home and in-clinic participation, participant must have the
linguistic proficiency to complete the proposed assessments
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. more than 2 lacunar infarcts.
b. Any territorial infarct greater then 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary objectives: see above<br /><br><br /><br>Primary endpoints:<br /><br>- Incidences of AEs, including AESIs and SAEs<br /><br>- Vital signs, clinical laboratory results, and incidence of findings from<br /><br>physical, neurological, ophthalmological exams, and ECG<br /><br>- C-SSRS<br /><br>- MRI abnormalities<br /><br>- Assess the effect of dose titration on ARI<br /><br>- Incidence of ADAs<br /><br>- Association of ADA titer with safety, PK, and PD parameters</p><br>
- Secondary Outcome Measures
Name Time Method <p>exploratory objectives: see above<br /><br><br /><br>exploratory endpoints:<br /><br>- CDR-SB<br /><br>- MMSE<br /><br>- RBANS-Update<br /><br>- ADAS-Cog13<br /><br>- ADCS-ADL-MCI<br /><br>- ADCOMS<br /><br>- Levels of sTREM2 in CSF and/or plasma<br /><br>- Levels of biomarkers related to microglia function in CSF and/or plasma (eg,<br /><br>CSF1R, IL1RN, osteopontin, YKL 40)<br /><br>- Levels of biomarkers related to AD pathology in CSF and/or plasma (eg, Aβ40,<br /><br>Aβ42, pTau, tTau)<br /><br>- Levels of neurodegeneration biomarkers in plasma and/or CSF eg, NfL<br /><br>- Brain volume, assessed by volumetric MRI<br /><br>- Brain pathological tau burden as assessed by longitudinal tau PET for<br /><br>participants who agree to participate in the optional assessment only<br /><br>- Brain amyloid burden as assessed by longitudinal amyloid PET scanning for<br /><br>participants who agree to participate in the optional assessment only</p><br>