Parkinson Disease
Conditions
Brief summary
This study is an open-label, single ascending dose escalation followed by a multiple administration dose at the maximal suitable dose (MSD). The investigational Medicinal Product (IMP) is given as an add-on therapy. Talineuren consists of GM1 (monosialotetrahexosylganglioside), the pharmacologically active ingredient, associated with a proprietary lipid formulation assembled as liposomes. The primary objective is to demonstrate the safety of TLN administration intravenously in Parkinson patients. Secondary objectives are the determination of the maximal suitable dose based on the safety profile and preliminary efficacy, as well as the determination of the pharmacokinetics (PK) profile.
Detailed description
The ganglioside lipid GM1 has been described in the literature as a neuroprotective agent. Several clinical studies have shown that GM1 improves the condition of Parkinson's disease patients. Talineuren consists of the pharmacologically active ingredient GM1, associated with a proprietary lipid formulation assembled as liposomes. Talineuren has been developed to improve the delivery and bioavailability of GM1. The primary objective of this trial is to demonstrate the feasibility and safety of intravenous Talineuren administration in Parkinson's disease patients. The secondary objectives are: * The determination of the recommended phase 2 dose based on the safety profile and preliminary efficacy. * The determination of the pharmacokinetics (PK) profile. This trial aims to investigate the safety of the novel formulation of GM1, Talineuren. To that extent a three-part trial was designed: Part 1- Dose escalation Part 2- Dose consolidation Part 3- Dose consolidation with intrapatient dosing Part 1- rapid dose escalation scheme from 6 mg to 720 mg of Talineuren formulated GM1 in 3 patients. Optional treatment prolongations for 8 weeks (Amendment 1), 16 weeks (Amendment 2), 8 months (Amendment 3), 4 months (Amendment 4), and 12 months (Amendment 5). Part 2- multiple dosing of Talineuren over 8 weeks in 9 patients to validate the safety profile of the maximum suitable dose. Optional treatment prolongations for 16 weeks (Amendment 2), 8 months (Amendment 3), 4 months (Amendment 4), and 12 months (Amendment 5). Part 3- rapid dose escalation scheme from 6 mg to 720 mg of Talineuren followed by multiple doses of 720mg Talineuren for up to 8 months in 10 patients (Amendment 3). Additional Follow-up visit (washout timepoint) 4 months after final assessment (Amendment 6).
Interventions
DRUGTalineuren
Talineuren is a liposomal formulation of the GM1 Ganglioside for intravenous administration
Sponsors
InnoMedica Schweiz AG
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part 1: dose escalation phase, 3 patients with Parkinson's disease, (2 cohorts as in 1+2 patients, sequential inclusion between the first and 2nd patient) Part 2: repeated dose administration phase, 9 patients with Parkinson's disease (1 cohort) Part 3: Dose consolidation with intrapatient dosing, 10 patients with Parkinson's disease (1 cohort)
Eligibility
Sex/Gender
ALL
Age
30 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent as documented by signature. * Confirmed Parkinson's disease according to British brain bank criteria. * Hoehn and Yahr Stage 0 - 2.5 on medication. * Stable on PD treatment for a month at least. * Absence of dementia confirmed by cognitive testing (MoCA \>25).
Exclusion criteria
* Contraindications to the class of drugs under study, e.g., known hypersensitivity or allergy to class of drugs or the investigational product. * Women who are pregnant or breast feeding, or planning to become pregnant during the course of the trial or in the 3 months following the trial. * Lack of safe contraception in women with childbearing potential * Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc) that is not under stable control. * Subject has an atypical parkinsonian syndrome or secondary parkinsonism. * Patients with comorbidity that may interfere with the course of the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurence of adverse events (safety) | 8 to 134 weeks | Number and kinds of adverse events (AEs) |
| Occurence of serious adverse events (safety) | 8 to 134 weeks | Number and kinds of serious adverse events (SAEs) |
| Occurence of other safety-related signs (safety) | 8 to 134 weeks | Number and kinds of other safety-related signs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Levodopa challenge (LDC) test | 8 to 134 weeks | Assessing the patients' condition via the LDC test (MDS-UPDRS-3 score) |
| Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) | 8 to 134 weeks | Assessing the patients' condition via the test |
| Epworth Sleepiness Scale (ESS) | 8 to 134 weeks | Assessing the patients' condition via the test |
| Parkinson's Disease Questionnaire (PDQ-39) | 8 to 134 weeks | Assessing the patients' condition via the test |
| Change in Parkinson's medication | 8 to 134 weeks | Assessing the patients' condition via the change in their pre-existing Parkinson's medication |
| Starkstein Apathy Scale (SAS) | 8 to 134 weeks | Assessing the patients' condition via the test |
| Montreal Cognitive Assessment (MoCA) | 8 to 134 weeks | Assessing the patients' condition via the test |
| Beck's Depression Inventory (BDI) | 8 to 134 weeks | Assessing the patients' condition via the test |
| Non-Motor Symptoms Questionnaire (NMSQuest) | 8 to 134 weeks | Assessing the patients' condition via the test |
| Maximum Observed Drug Concentration (Cmax) in serum | 8 to 15 weeks | Pharmacokinetics (PK) of total GM1 in serum over the first 96 h |
| Time of Maximum Drug Concentration (Tmax) in serum | 8 to 15 weeks | Pharmacokinetics (PK) of total GM1 in serum over the first 96 h |
| Area Under the Curve to infinity (AUCinf.) in serum | 8 to 15 weeks | Pharmacokinetics (PK) of total GM1 in serum over the first 96 h |
| half-life (t1/2) | 8 to 15 weeks | Pharmacokinetics (PK) of total GM1 in serum over the first 96 h |
| Clearance (CL) | 8 to 15 weeks | Pharmacokinetics (PK) of total GM1 in serum over the first 96 h |
| Volume of distribution (Vd) | 8 to 15 weeks | Pharmacokinetics (PK) of total GM1 in serum over the first 96 h |
Countries
Switzerland
Outcome results
None listed