This study has been transitioned to CTIS with ID 2023-506872-29-00 check the CTIS register for the current data. The primary objectives of this add-on Phase 2 LTE study (see Table 1) are to evaluate the long-term safety and tolerability of IMP at…
ID
Source
Brief title
Condition
- Mental impairment disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objectives: see above
Primary endpoints:
- 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 ARI
- Incidence of ADAs
- Association of ADA titer with safety, PK, and PD parameters
Secondary outcome
exploratory objectives: see above
exploratory endpoints:
- 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, Aβ40,
Aβ42, 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
Background summary
The worldwide prevalence of dementia is expected to exceed 130 million by 2050.
Alzheimer*s disease (AD) is a degenerative brain disease and is the
most common cause of dementia in the US, affecting approximately 5.8 million
Americans as of 2019. Current therapies for AD such as acetylcholinesterase
inhibitors (eg, donepezil) and N-methyl-D-aspartate receptor antagonists (eg,
memantine) show only modest and transient
benefits to cognition and behavior parameters in AD patients but do not slow or
halt the progression of the disease. Human genetic studies have identified
inherited mutations that underlie familial forms of AD, but these mutations are
rare, occurring in less than 5% of all cases. More recently, large human
genetic association studies have revealed genetic loci that modify the risk of
common sporadic forms of AD. Many of these loci encode for proteins expressed
primarily on innate immune cells, including microglia, which are resident
macrophages of the central nervous system (CNS) and serve protective
housekeeping functions such as facilitating clearance of cellular debris
through phagocytosis, maintaining synapses, and secreting growth factors. Thus,
in the course of neurodegenerative diseases such as AD, these cells may serve
an important protective role when activated appropriately. The most prominent
microglial gene that modifies the risk of common sporadic forms of AD encodes
for a triggering receptor expressed on myeloid cells 2 (TREM2). Alector*s
approach is to utilize a TREM2 agonistic antibody to ameliorate AD pathology
through activation of the innate immune system, thereby improving the clearance
and sequestration of the molecular factors causing pathology.
Study objective
This study has been transitioned to CTIS with ID 2023-506872-29-00 check the CTIS register for the current data.
The primary objectives of this add-on Phase 2 LTE study (see Table 1) are to
evaluate the long-term safety and tolerability of IMP at three possible doses
(ie, 15 mg/kg, 40 mg/kg, and 60 mg/kg) and to assess the effect of dose
titration on the incidence and severity of amyloid-related imaging abnormality
(ARIA). The exploratory objectives of this AL002- LTE study are to evaluate the
efficacy of IMP with clinical outcome assessments (COAs) and biomarkers.
Study design
This is a Phase 2, randomized, parallel-group, long-term extension (LTE),
dose-blind, multicenter study to evaluate the long-term safety and efficacy of
AL002 [referred to as investigational medicinal product (IMP) in this AL002-LTE
study] in participants with AD. The study is a multicenter, global
trial that will enroll participants who completed the planned treatment period
in AL002-2 (parent study).
Screening/baseline (day -28 to -1): consent procedure and screening
Treatment period: day 1/week 1 to week 49: IP is administered by infusion every
4 weeks. All participants who received placebo in the parent study will now
receive IP according to a titration algorithm.
EOT visit: 8 weeks after last visit week 49.
The study is double-blind to dose.
Intervention
AL002 is een recombinant gehumaniseerd monoklonaal antilichaam, dat een
agonistisch TREM2 monoklonaal antilichaam is.
Study burden and risks
Burden:
- 20 visits, including screening and EOT visit, 13 study visits (where IP is
administered) and 5x a short visit for an MRI
- answering questionnaires, which can be confrontational/a psychological burden
- the optional procedures: 2x CSF, 2x TAU pet scan, 2x amyloid PET scan. The
patient can decide not to participate at all or to participate in certain
procedures and not others.
- 5 MRI scans
- blood tests as described at E6.
IP related risks:
especially ARIA related. Further:
- headache
- nausea
- infection of the upper respiratory tract
- pain where needles have penetrated the skin
- backache
- vomit
- dizziness
- tingling sensation on the skin
- headache after lumbar puncture.
- infusion-related reactions
- fatigue
Risks related to the following procedures:
- blood test
- Lumbar puncture
- discomfort during imaging scans
- radiation
- risk of developing ABs
- infusion risks
- eye exam risks
- allergic reactions
- psychological risks
- privacy risks.
131 Oyster Point Blvd suite 600
South San Francisco CA 94080
US
131 Oyster Point Blvd suite 600
South San Francisco CA 94080
US
Listed location countries
Age
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.
12. For at-home and in-clinic participation, participant must have the
linguistic proficiency to complete the proposed assessments and other clinical
rating scale
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. 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-506872-29-00 |
| EudraCT | EUCTR2022-002987-57-NL |
| CCMO | NL82866.056.22 |