Idiopathic Parkinson's Disease MedDRA version: 21.1 Level: LLT Classification code 10013113 Term: Disease Parkinson's System Organ Class: 100000004852
Conditions
Sponsors
Herantis Pharma Plc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Completion of the 6 months treatment period in the Main study (HP-CD-CL-2002), including End-of-Study assessment at Visit 17 (Week 24). 2. Females of childbearing potential must have a negative pregnancy test at study entry and be willing to use a highly effective form of contraception until 30 days after the end of the study (hormonal contraception associated with inhibition of ovulation, IUD, IUS, bilateral tubal occlusion, vasectomised partner or sexual abstinence). Males (non-vasectomised) must be willing to use condom during intercourse and do not donate sperms for three months following each DAT-PET scan. Female partners of childbearing potential should be willing to use a highly effective form of contraception until 30 days after their male partner’s end of the study. 3. At least one functioning catheter tip in each putamen. 4. Provision of informed consent. The patient is judged by the investigator to be alert and oriented to person, place, time and situation when giving the informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 9 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 9
Exclusion criteria
Exclusion criteria: 1. Drug-resistant rest tremor, severe dyskinesia or severe head tremor, which could interfere with treatment infusions. 2. Significant neurological disorder other than PD including clinically significant head trauma, cerebrovascular disease, epilepsy, CSF shunt or other implanted central nervous system (CNS) device. 3. Changes in pathology which give rise to safety concern such as sequelae from catheter implantation, clinically significant intracerebral trauma, oedema, haemorrhage, or infection. 4. Current psychosis requiring therapy. Brief episodes of hallucinations, disorientation or confusion are not exclusionary. 5. Presence of clinically significant impulse control disorder by a positive screen on the questionnaire for impulsive-compulsive disorders in Parkinson’s Disease (QUIP-RS) score >20, or, presence of dopamine dysregulation syndrome. 6. Any unresolved intolerable adverse events or adverse device events in study HP-CD-CL-2002, which are not expected to resolve or cease to an acceptable level of intensity within reasonable time. This includes any Serious Adverse Event (SAE) of at least Grade 3 (severe) in severity, judged to be possibly, probably or definitely related to study treatment. 7. Any medical condition, which might impair outcome measure assessments or safety measures including ability to undergo MRI or DAT-PET. 8. Impaired renal function. Estimated Glomerular Filtration rate (eGFR) < 30 mL/min/1.73 m2 . 9. Concomitant treatment with neuroleptics or antipsychotic medication prescribed for treatment of current psychosis, central dopamine blockers or tricyclic antidepressants. Low dose quetiapine and similar medications prescribed for Parkinson’s disease treatment are not exclusionary.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the safety and tolerability of – the IMP administered as long-term monthly intermittent bilateral intraputamenal CDNF infusions, and, – the investigational medical device for the intended long-term use and within the intended patient population during infusions. ;Secondary Objective: Drug related: • Severity of PD motor symptoms as measured by OFF-state UPDRS part III • Mobility as measured by OFF-state Timed Up and Go (TUG) test • ON-state non-motor and motor function, motor complications, and ON- and OFF-state activities of daily living as measured by UPDRS scores part I-IV • Patient’s functional status by home diary • Patient’s health and daily activities as measured by PDQ-39 questionnaire • Patient’s treatment response on mental status as measured by CGI scale Device related: • the patency of each individual catheter lines and the whole system • the stability of the transcutaneous port Exploratory objectives Drug related: • DAT-PET imaging • Serum and cerebrospinal fluid levels of a-synuclein • Daily activity measurement by Parkinson’s KinetiGraph • Level of distribution of CDNF and proteomic biomarker screen in CSF • Genome sequencing testing from saliva Device related: • the coverage of infusion at the target site;Primary end point(s): DRUG RELATED • Change from extension study start (Week 24) until end of treatment evaluation (Week 49) in adverse events (AEs), Electrocardiogram (ECGs), Beck Depression Inventory (BDI) score, questionnaire for impulsive-compulsive disorder in Parkinson’s disease rating scale (QUIP-RS), Montreal cognitive assessment (MoCA) score, physical examination, vital signs, clinical laboratory variables and CDNF-antibody testing in serum. DEVICE RELATED • Occurrence of adverse device effects (ADE), for either the whole system or the individual sub systems (guide tubes/catheters, subcutaneous components, port), evaluated separately for the infusion proc | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): DRUG RELATED • Change from baseline (Week -1), at study start (Week 24), after three months (Week 37), and end of treatment evaluation (Week 49) in severity of PD motor symptoms by UPDRS Part III motor scores. • Change from baseline (Week -1), at study start (Week 24), after three months (Week 37), and end of treatment evaluation (Week 49) in mobility by TUG test. • Change from baseline (Week -1), at study start (Week 24), after three months (Week 37), and end of treatment evaluation (Week 49) in severity of PD non-motor and motor symptoms by UPDRS Part I-IV total scores (Parts I, II and IV in ON-state; Part III in OFF-state). • Change from baseline (Week -1), at study start (Week 24) until end of treatment evaluation (Week 49) in functional status by home diary score. • Change from baseline (Week -1), at study start (Week 24), after three months (Week 37), and end of treatment evaluation (Week 49) in health and daily activity by PDQ-39 questionnaire score. • Change from baseline (Week -1), at study start (Week 24) and end of treatment evaluation (Week 49) in mental status as measured by CGI scale. DEVICE RELATED • Occurrence of blockage of an individual implanted catheter preventing or limiting infusion (Week 25) until final treatment infusion (Week 45) as measured by pressure rise above 590 mmHg. • Cessation of infusions in an individual patient due to: o the inability to secure an external system due to looseness of the port, o the need for surgical removal of the transcutaneous port or surgical intervention to stabilise the port. Exploratory Endpoints DRUG RELATED 1) Change in caudate and putamen DAT availability prior to dosing (Week -2) to 12 months of dosing (Week 47) using PET imaging with [ 18 F]FE-PE2I to assess the integrity of the nigrostriatal system. 2) Change in serum and cerebrospinal fluid levels of to | — |
Countries
Finland, Sweden
Contacts
Public ContactProject Manager
Herantis Pharma Plc
Outcome results
None listed