Safety Evaluation of Intravenous Talineuren (TLN) in Parkinson's Disease-affected Patients

Parkinson Disease Clinical Trial

— NEON  

Official title:

Safety Evaluation of Intravenous Talineuren (TLN) in Parkinson's Disease-affected Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04976127
• Other study ID #: TLN/PD/1
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 7, 2021
• Est. completion date: August 2025

Study information

• Verified date: March 2024
• Source: InnoMedica Schweiz AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 22
• Est. completion date: August 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• Talineuren
Talineuren is a liposomal formulation of the GM1 Ganglioside for intravenous administration

Locations

Country	Name	City	State
Switzerland	Neurologisches Institut Konolfingen	Konolfingen	Bern

Sponsors (1)

Lead Sponsor	Collaborator
InnoMedica Schweiz AG

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurence of adverse events (safety)	Number and kinds of adverse events (AEs)	8 to 134 weeks
Primary	Occurence of serious adverse events (safety)	Number and kinds of serious adverse events (SAEs)	8 to 134 weeks
Primary	Occurence of other safety-related signs (safety)	Number and kinds of other safety-related signs	8 to 134 weeks
Secondary	Levodopa challenge (LDC) test	Assessing the patients' condition via the LDC test (MDS-UPDRS-3 score)	8 to 134 weeks
Secondary	Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	Assessing the patients' condition via the test	8 to 134 weeks
Secondary	Epworth Sleepiness Scale (ESS)	Assessing the patients' condition via the test	8 to 134 weeks
Secondary	Parkinson's Disease Questionnaire (PDQ-39)	Assessing the patients' condition via the test	8 to 134 weeks
Secondary	Change in Parkinson's medication	Assessing the patients' condition via the change in their pre-existing Parkinson's medication	8 to 134 weeks
Secondary	Starkstein Apathy Scale (SAS)	Assessing the patients' condition via the test	8 to 134 weeks
Secondary	Montreal Cognitive Assessment (MoCA)	Assessing the patients' condition via the test	8 to 134 weeks
Secondary	Beck's Depression Inventory (BDI)	Assessing the patients' condition via the test	8 to 134 weeks
Secondary	Non-Motor Symptoms Questionnaire (NMSQuest)	Assessing the patients' condition via the test	8 to 134 weeks
Secondary	Maximum Observed Drug Concentration (Cmax) in serum	Pharmacokinetics (PK) of total GM1 in serum over the first 96 h	8 to 15 weeks
Secondary	Time of Maximum Drug Concentration (Tmax) in serum	Pharmacokinetics (PK) of total GM1 in serum over the first 96 h	8 to 15 weeks
Secondary	Area Under the Curve to infinity (AUCinf.) in serum	Pharmacokinetics (PK) of total GM1 in serum over the first 96 h	8 to 15 weeks
Secondary	half-life (t1/2)	Pharmacokinetics (PK) of total GM1 in serum over the first 96 h	8 to 15 weeks
Secondary	Clearance (CL)	Pharmacokinetics (PK) of total GM1 in serum over the first 96 h	8 to 15 weeks
Secondary	Volume of distribution (Vd)	Pharmacokinetics (PK) of total GM1 in serum over the first 96 h	8 to 15 weeks