Clinical trial NCT04976127: Safety Evaluation of Intravenous Talineuren (TLN) in Parkinson's Disease-affected Patients
Official title: Safety Evaluation of Intravenous Talineuren (TLN) in Parkinson's Disease-affected Patients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Parkinson Disease
Lead sponsor: InnoMedica Schweiz AG
Sponsor class: INDUSTRY
First posted: 2021-07-26
Enrollment: 22
Sex: ALL
Minimum age (years): 30
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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)
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Occurence of adverse events (safety)
timeFrame: 8 to 134 weeks
measure: Occurence of serious adverse events (safety)
timeFrame: 8 to 134 weeks
measure: Occurence of other safety-related signs (safety)
timeFrame: 8 to 134 weeks
Secondary outcomes:
measure: Levodopa challenge (LDC) test
timeFrame: 8 to 134 weeks
measure: Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
timeFrame: 8 to 134 weeks
measure: Epworth Sleepiness Scale (ESS)
timeFrame: 8 to 134 weeks
measure: Parkinson's Disease Questionnaire (PDQ-39)
timeFrame: 8 to 134 weeks
measure: Change in Parkinson's medication
timeFrame: 8 to 134 weeks
measure: Starkstein Apathy Scale (SAS)
timeFrame: 8 to 134 weeks
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: 8 to 134 weeks
measure: Beck's Depression Inventory (BDI)
timeFrame: 8 to 134 weeks
measure: Non-Motor Symptoms Questionnaire (NMSQuest)
timeFrame: 8 to 134 weeks
measure: Maximum Observed Drug Concentration (Cmax) in serum
timeFrame: 8 to 15 weeks
measure: Time of Maximum Drug Concentration (Tmax) in serum
timeFrame: 8 to 15 weeks
measure: Area Under the Curve to infinity (AUCinf.) in serum
timeFrame: 8 to 15 weeks
measure: half-life (t1/2)
timeFrame: 8 to 15 weeks
measure: Clearance (CL)
timeFrame: 8 to 15 weeks
measure: Volume of distribution (Vd)
timeFrame: 8 to 15 weeks
Other outcomes:
Locations:
city: Konolfingen
country: Switzerland
facility: Neurologisches Institut Konolfingen
state: Bern
Study officials:
References: