Parkinson's Disease
Conditions
Brief summary
An unblinded, single arm, pilot observational study to test the safety, tolerability, immunogenicity and the biological effects of TRB-001 vaccination in individuals who have previously undergone aSyn immunotherapy
Interventions
BIOLOGICALTRB-001
This is an unblinded, single arm, pilot observational study to test the safety, tolerability, immunogenicity and the biological effects of TRB-001 vaccination in individuals who have previously undergone aSyn immunotherapy. After the screening period, all participants who are enrolled in the study will receive a first intradermal TRB-001 immunization at a dose of 100μg. Patients antibody response will be assessed at week two (compared to baseline). Based on the safety and immunogenicity results, the PI, Medical Monitor, and Sponsor will decide on a potential second immunization with TRB-001. Regarding immunogenicity, a predefined cut-off will be used. The patient may be offered another injection to be applied 4-6 weeks after the first immunization with TRB-001. Participants will be evaluated at week 24. Assessments will include safety, immunogenicity, blood-/CS
Sponsors
Tridem Bioscience FlexCo
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18-years of age * Female or male with previous treatment with active aSyn immunotherapy * Parkinson's disease diagnosis (any stage) * Understands and agrees to comply with the study procedures and provides written informed consent
Exclusion criteria
* Women of childbearing potential without use of contraception * Women who are pregnant or lactating * Contraindication for MRI or lumbar puncture * Known or suspected allergy, or history of anaphylaxis, to vaccines or their excipients, if considered relevant by the investigator * Presence or history of autoimmune disease or immunodeficiency, if considered relevant by the investigator * Presence of active infectious disease (hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)) * Significant cognitive impairment or clinical dementia, or a Montreal Cognitive Assessment (MoCA) score \<26 * High suspicion of other parkinsonian syndromes, such as multiple system atrophy, progressive supranuclear palsy, drug-induced Parkinsonism and post-encephalitic Parkinsonism * Any relevant systemic illness. This includes cardiovascular, hepatic, gastroenterological, respiratory, endocrinological, hematologic disease, or any other condition that, in the investigator's opinion, could interfere with the analyses of safety and efficacy in this study, unless patient has been on stable doses of medication for any of these concurrent illnesses for at least 3 months prior to study entry * Unstable psychiatric illness, including psychosis, suicidal ideation, untreated major depression, schizophrenia, or bipolar affective disorder within 90 days before Visit 1, as determined by the investigator * History of drug or alcohol abuse within the past 5 years * Recent history (≤2 years) of cancer (exceptions; basal cell carcinoma, intraepithelial cervical neoplasia) * Birthmarks, tattoos, wounds, or skin conditions that may obscure the assessment of injection site reactions * Participation in the active treatment phase of any non-PD clinical trial within 30 days prior to Visit 1 * Dose limiting toxicity to previous immunization with aSyn-based PD vaccine * Current immunosuppressive therapy * Employee at the study site, spouse/partner or relative of any study staff (e.g. investigator, sub-investigators, or study nurse) or relationship to sponsor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of local and systemic treatment-emergent adverse events (TEAEs) | 6 months | Incidence of local and systemic treatment-emergent adverse events (TEAEs) (occurrence, intensity, duration, and relationship to IMP) over 6-months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Titers of vaccine-induced antibodies in blood and CSF | 6 months | Titers of vaccine-induced antibodies (immunizing peptide, aSyn monomer; area under the curve for both parameters) in blood and CSF (peptide only) over 6 months compared to baseline |
| Change from baseline in total aSyn levels | 6 months | Change from baseline in total aSyn levels as assessed by ELISA in blood and CSF |
| Change in levels of aggregated aSyn in blood and CSF | 6 months | Change from baseline in levels of aggregated aSyn in blood and CSF |
| Change in GFAP and Neurofilament light chain in CSF | 6 months | Change from baseline in GFAP and Neurofilament light chain in CSF |
| Avidity of antibodies induced for aggregated aSyn | 6 months | Avidity of antibodies induced for aggregated aSyn as assessed after the vaccination with TRB-001 compared to baseline |
| Selectivity of antibodies induced by TRB-001 | 6 months | Selectivity of antibodies induced by TRB-001 for aggregated aSyn |
| Change from baseline of the seed amplification assay signal (CSF) | 6 months | Change from baseline of the seed amplification assay signal (CSF) |
| Correlation between measures of the antibody response | 6 months | Correlation between measures of the antibody response (peptide titer, aSyn titer, avidity, titers x avidity, selectivity and biomarkers of the disease) (change from baseline in total aSyn levels, levels of aggregated aSyn in blood and CSF) |
| Change in MDS-UPDRS I, II, III, and IV | 6 months | Change from baseline in MDS-UPDRS I, II, III, IV |
| Change from baseline in PD symptoms | 6 months | Change from baseline in PD symptoms using the wearable device STAT-ON(TM) |
| Change in symptomatic PD medication | 6 months | Change from baseline in symptomatic PD medication (Levodopa equivalent dose) |
| Change in levels of circulating extracellular vesicle (EV)-based biomarkers | 6 months | Change from baseline in Levels of circulating extracellular vesicle (EV)-based biomarkers |
| Change in the number of vaccine specific B- and T cell clones | 6 months | Change from baseline in the number of vaccine specific B- and T cell clones as assessed by B/T cell receptor sequencing |
| Incidence of local and systemic TEAEs | 12 months | Incidence of local and systemic TEAEs over 12- months |
| Change from baseline in levels of aggregated aSyn in blood | 12 months | Change from baseline in levels of aggregated aSyn in blood |
| Titers of vaccine-induced antibodies in blood | 12 months | Titers of vaccine-induced antibodies (immunizing peptide, aSyn monomer; area under the curve for both parameters) in blood |
| Change from baseline in MDS-UPDRS I, II, III, IV at 12 month time period | 12 months | Change from baseline in MDS-UPDRS I, II, III, IV |
| Change from baseline in PD symptoms at 12 month time period | 12 months | Change from baseline in PD symptoms using the wearable device STAT-ONTM |
| Change from baseline in symptomatic PD medication at 12 month time period | 12 months | Change from baseline in symptomatic PD medication (Levodopa equivalent dose) Change from baseline in the number of vaccine specific B- and T cell clones as assessed by B/T cell receptor sequencing |
Countries
Austria
Contacts
CONTACTMarkus Mandler
STUDY_DIRECTORAchim Schneeberger, Dr.
Tridem Bioscience FlexCo
Outcome results
None listed