Healthy Adult Participants, MSA - Multiple System Atrophy, Parkinson Disease (PD)
Conditions
Keywords
MODAG, MODAG GmbH, Synuclein, Neurodegeneration, Lewy Body
Brief summary
This is an open-label, single-center Phase 1 study evaluating the safety, tolerability, and test-retest characteristics of \[11C\]MODAG-005, an investigational positron emission tomography/computed tomography (PET/CT) radioligand intended to image pathological alpha-synuclein deposition in the brain. The study will enroll participants with Parkinson's disease (PD), participants with multiple system atrophy (MSA), and age-matched healthy controls (AMHC). Participants with PD or MSA will undergo two \[11C\]MODAG-005 PET/CT imaging sessions: one baseline scan and one follow-up scan 7 to 48 days later. Age-matched healthy controls will undergo one baseline scan. A subset of PD and MSA participants will receive a single oral dose of anle138b (Emrusolmin) before the second scan to evaluate tracer uptake under blocking conditions. The primary objective is to assess the safety and tolerability of \[11C\]MODAG-005. Secondary objectives include evaluating whether \[11C\]MODAG-005 PET imaging can distinguish participants with MSA or PD from age-matched healthy controls, distinguish PD from MSA, and determine test-retest variability of PET outcome measures.
Detailed description
This is an open-label, single-center Phase 1 study evaluating \[11C\]MODAG-005, an investigational Positron Emission Tomography (PET) radioligand for imaging pathological alpha-synuclein deposition in the brain. The study will enroll participants with Parkinson's disease (PD), participants with multiple system atrophy (MSA), and age-matched healthy controls (AMHC). Participants with PD or MSA will undergo two \[11C\]MODAG-005 PET/CT scans: a baseline scan and a follow-up scan 7 to 48 days later. Age-matched healthy controls will undergo one baseline PET/CT scan. A subset of PD and MSA participants will receive a single oral dose of 300 mg anle138b (Emrusolmin) before the second scan to evaluate tracer uptake under blocking conditions. The primary objective is to assess the safety and tolerability of \[11C\]MODAG-005 based on adverse events, vital signs, physical examinations, laboratory tests, and electrocardiograms. Secondary objectives include evaluating whether \[11C\]MODAG-005 PET imaging can distinguish MSA from healthy controls, PD from healthy controls, and PD from MSA, and assessing test-retest variability of PET imaging measures. Exploratory analyses will assess tracer uptake with and without anle138b blocking, blood radioactivity and metabolite profiles, image-derived input functions, visual PET reads, and relationships between PET signal and clinical measures. Total study participation will last up to 12 weeks from screening to final follow-up.
Interventions
DRUG[11C]MODAG-005
Injection of \[11C\]MODAG-005 followed by PET imaging.
Sponsors
MODAG GmbH
Universität Tübingen
ABX CRO
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Key inclusion criteria: Patients with MSA fulfilling both the criteria for probable MSA (Gilman et al., 2008) and clinically established MSA (Wenning et al., 2022), patients with PD fulfilling the criteria for clinically established PD (Postuma et al., 2015) or age-matched healthy controls (AMHC).
Exclusion criteria
1. Laboratory tests with clinically significant abnormalities and/or clinically significant unstable medical illness equivalent to CTC v5.0 (common toxicity criteria) toxicities greater than grade 2. 2. Evidence of clinically significant disease that is expected to interfere with cognitive assessments or the ability to complete the trial procedures as judged by the investigator. 3. Clinically significant renal and hepatic dysfunction as judged by the investigator. 4. Known hypersensitivity to the active substance or to any of the excipients of \[11C\]MODAG-005 solution for injection. 5. Known hypersensitivity to the active substance or to any of the excipients in anle138b (Emrusolmin) capsules. 6. Participant has received an investigational drug within 3 months of screening. 7. Blood donations within 7 days before enrolment. 8. Pregnant (see 9.1.5) or breast-feeding or having the intention of getting pregnant. Female participants of childbearing potential and male participants with female partners of childbearing potential not willing to practice effective contraception during the trial period and for 90 days following each PET/CT scan. 9. Unsuitable veins for repeated venipuncture. 10. Contraindication to blood sampling and/or arterial cannulation, including but not limited to allergy to local anesthetics, peripheral vascular disease, Raynaud's phenomenon as determined by abnormal Allen's test on both arms or abnormal coagulation profile at screening. If Allen's test should be "abnormal" on both arms, the participant will not be eligible for arterial sampling, but will participate in the remaining assessments. 11. MRI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | Inclusion to 4 days (± 2 days) post injection. | AEs related to the medication |
| Safety and tolerability | Inclusion to 4 days (± 2 days) post injection. | AEs leading to discontinuation/drop-out rates |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the ability of [11C]MODAG-005 to discriminate between MSA and HC. | Slots between 0 and 90 minutes after tracer injection. | Standardized uptake value ratio (SUVR) for different imaging time windows, volume of distribution (VT) and distribution volume ratio (DVR) in different brain regions between participants with MSA and AMHC from PET acquisitions after administration of \[11C\]MODAG-005. |
| To assess the ability of [11C]MODAG-005 to discriminate between PD and HC | Slots between 0 and 90 minutes after tracer injection. | SUVR for different imaging time windows, VT, and DVRin different brain regions between patients with PD and AMHC from PET acquisitions after administration of \[11C\]MODAG-005. |
| To assess the ability of [11C]MODAG-005 to discriminate between PD and MSA | Slots between 0 and 90 minutes after tracer injection. | SUVR for different imaging time windows, VT, and DVR in different brain regions between participants with PD and participants with MSA from PET acquisitions after administration of \[11C\]MODAG-005. |
| To determine test-retest variability in PD and MSA under blocking conditions. | 8-49 days after first tracer injection. | Test-retest variability of SUVR for different time imaging time windows and DVR after administration of \[11C\]MODAG-005 in PD and MSA under blocking with a single dose of Emrusolmin 300 mg. |
Countries
Germany
Contacts
CONTACTJohannes Levin, MD
Outcome results
None listed