Alpha-Synucleinopathy, Dementia With Lewy Bodies, Multisystem Atrophy, Parkinson's Disease
Conditions
Brief summary
The overall goal of this protocol is to evaluate \[18F\]MNI-1216 (also known as \[18F\]ACI-12589) as an α-synuclein targeted radiopharmaceutical in 3 parts as follows: * Part 1: first in human (FiH) imaging * Optional Part 2: expansion of FiH imaging * Optional Part 3: retest imaging A total of up to 30 participants may be enrolled and participate in the study. Part 1 of the study will include up to 10 participants (target of up to 5 healthy volunteers and up to 5 participants with idiopathic Parkinson's Disease). There will be an ongoing review of study data in Part 1 to evaluate the characteristics of tracer binding and safety. If the study results are deemed adequate in Part 1, Part 2 and/or Part 3 may be initiated. The decision to initiate Part 3 may also include a review of data from Part 2, if Part 2 is performed and the data are available. If performed, Part 2 will include up to 20 participants, including health volunteers and participants with α-synucleinopathies to acquire additional tracer-related data. If performed, Part 3 will include up to 10 participants from in Part 1 and/or Part 2 (including health volunteers and participants with α-synucleinopathies) to evaluate the reliability of \[18F\]MNI-1216 (\[18F\]ACI-12589) Positron Emission Tomography (PET) imaging.
Detailed description
The overall goal of this protocol is to evaluate \[18F\]MNI-1216 (also known as \[18F\]ACI-12589) as an α-synuclein targeted radiopharmaceutical in 3 parts. The specific objective for Parts 1, 2, and 3 is: • To characterize \[18F\]MNI-1216 (\[18F\]ACI-12589) as a PET radioligand for imaging α-synuclein pathology. The additional specific objectives for Part 1 and Part 2 are: * To visually and quantitatively assess brain uptake and pharmacokinetics of \[18F\]MNI-1216 (\[18F\]ACI-12589) as a PET imaging marker for α-synuclein pathology in individuals with α-synucleinopathies (including idiopathic PD) compared with corresponding data from healthy volunteer participants. * To evaluate the safety of a single injection of \[18F\]MNI-1216 (\[18F\]ACI-12589). The additional specific objectives for Part 3 are: * To evaluate the reliability (test/retest) of \[18F\]MNI-1216 (\[18F\]ACI-12589) parameters in individuals with α-synucleinopathies and healthy volunteers. * To evaluate the safety of up to 2 injections of \[18F\]MNI-1216 (\[18F\]ACI-12589). For each subject participating in the study, the duration of study participation will be up to 78 days. In Part 1 and Part 2 (if Part 2 is performed), screening assessments will occur within 30 days prior to the Baseline \[18F\]MNI-1216 (\[18F\]ACI-12589) Imaging Visit (Day 1). If determined to be necessary by the study team, subjects may participate in an \[18F\]Florbetapir Imaging Visit up to 6 weeks following Day 1 (will be completed between Day 2 and Day 42). A Safety Phone Call for adverse event assessment will occur 4 days (±2 days) following each imaging visit performed. In Part 3 (if performed), subjects will participate in a Retest \[18F\]MNI-1216 (\[18F\]ACI-12589) Imaging Visit between Day 4 and Day 29 (within 3 days to 4 weeks) following the Baseline \[18F\]MNI-1216 (\[18F\]ACI-12589) Imaging Visit (Day 1). A Safety Phone Call for adverse event assessment will occur 4 days (±2 days) following the retest imaging visit, if performed.
Interventions
DRUG[18F]MNI-1216
\[18F\]MNI-1216 is an intravenously administered radioactive imaging agent being studied as a potential positron emitting radiopharmaceutical for in vivo imaging of α-synuclein deposits.
Sponsors
AC Immune SA
Invicro
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
The study population will be composed of up to 30 subjects, including healthy volunteers and participants with α-synucleinopathies.
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Participants is able to provide written informed consent, which must be obtained before any assessment is performed. * Female participants must not be of childbearing potential, or agree to use contraception and not donate eggs if of childbearing potential. At the discretion of the Investigator, participants without documentation of non-childbearing potential may receive pregnancy testing. * A woman is considered to be of childbearing potential if postmenarchal, has not reached a postmenopausal state (12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (ie, removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the PI (eg, Müllerian agenesis). * Women of childbearing potential must commit to remain abstinent (refrain from heterosexual intercourse) or use 2 forms of birth control, 1 of which is a barrier contraception method, for the duration of the study and 30 days after study completion. Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. * Women of childbearing potential must commit to not donate ovum for the duration of the study and 30 days after study completion. * Male participants and their partners of childbearing potential must commit to the use of 2 methods of contraception, 1 of which is a barrier method for male participants for the study duration and 90 days after study completion. * Male participants must not donate sperm for the study duration and for 90 days after study completion. * Willing and able to cooperate with study procedures. * For participants receiving arterial cannulation, adequate circulation to the hand for safe placement of arterial line (as determined by Allen's test) and blood clotting (PT and PTT). * If participant takes bupropion, participant must agree to hold this medication for at least 12 hours prior to DaTscan imaging (if performed). Additional Inclusion Criteria for healthy volunteers: * Males and females aged ≥ 21 years. * Healthy with no clinically relevant finding on physical examination at Screening and upon reporting to the clinic for the \[18F\]MNI-1216 (\[18F\]ACI-12589) Imaging Visit. * No family history of α-synucleinopathy, including PD, or other early-onset neurological disease associated with dementia. * No personal history of clinically significant neurologic and/or psychiatric disorders. * No evidence of dopamine transporter deficit on DaTscan performed either as part of Screening or on previously acquired DaTscan (within 6 months prior to signing consent). * Have a Montreal Cognitive Assessment (MoCA) score ≥ 26. * No cognitive impairment as judged by the PI. Additional Inclusion Criteria for Participants with α-synucleinopathy: * Males and females aged ≥ 40 years. * Participants diagnosed with any of the following: * Idiopathic Parkinson's Disease * Parkinson's Disease with genetic risk factor (except leucine-rich repeat kinase 2 \[LRRK2\] mutation) * Dementia with Lewy Bodies * Multisystem Atrophy * A brain MRI consistent with a diagnosis of α-synucleinopathy, with no evidence of focal disease to account for the participant's neurological symptoms or MRI
Exclusion criteria
listed below under
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Volume of distribution (VT) of [18F]MNI-1216 across multiple brain regions | up to 78 days | Volume of distribution (VT) across multiple brain regions will be measured and comparison between participants with α-synucleinopathies and healthy volunteers will be performed to visually and quantitatively assess brain uptake and pharmacokinetics of \[18F\]MNI-1216 (\[18F\]ACI-12589) as a PET imaging marker for α-synuclein pathology in individuals with α-synucleinopathies. |
| Number of participants with [18F]MNI-1216-related adverse events as assessed by CTCAE | up to 78 days | Participants will be monitored to evaluate the safety of a single injection of \[18F\]MNI-1216 (\[18F\]ACI-12589). The following assessments will be performed to monitor participants for adverse reactions: * Clinical laboratory tests. * Vital signs. * Physical findings. * Electrocardiograms |
Other
| Measure | Time frame | Description |
|---|---|---|
| Average variability across subjects | up to 78 days | To evaluate the reliability (test/retest) of parameters in individuals with α-synucleinopathies and healthy volunteers, Investigators will calculate the average and standard deviation of variability across subjects based on imaging data ((test - retest) / average (test, retest)). |
| Intraclass correlation (ICC) of test and retest scans | up to 78 days | To evaluate the reliability (test/retest) of parameters in individuals with α-synucleinopathies and healthy volunteers, Investigators will calculate the intraclass correlation of test and retest scans from imaging data. Intraclass correlation is a reliability index in test/retest analyses. |
Countries
United States
Outcome results
None listed