Idiopathic Parkinson's disease (PD) of moderate severity (modified Hoehn & Yahr Stage IIb - III)
Conditions
Interventions
Product Name: sNN0031
Product Code: sNN0031
Pharmaceutical Form: Concentrate for solution for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo:
Sponsors
NeuroNova AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female. Females should either be post-menopausal (at least 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with FSH levels >40 mIU/mL), be surgically sterilized (bilateral oophorectomy w/o hysterectomy), or use adequate contraception (oral contraceptives, intrauterine device or double barrier contraception, i.e., condom + diaphragm, condom or diaphragm + spermicidal gel or foam.) during the duration of the study. - Diagnosis of idiopathic Parkinson's disease (PD) of moderate severity (modified Hoehn & Yahr Stage IIb-III). - Effect duration of oral L-dopa dose intake =4 hours - Score =30 on motor part (part III) of UPDRS at defined off (>12 hours after last dose intake) - Dopaminergic responsiveness with at least 33% decrease in the UPDRS part III score after administration of L-dopa - Disease duration at least 5 years - Age 30 to 75 years - Stable anti-Parkinson treatment for at least 3 months - Ophthalmologic examination with normal findings regarding vascular structure and function - MRI examination of the brain and cervical spinal cord within 3 months before anticipated implantation of the device with no findings of tumors or potential sources of pathological bleedings, or abnormality that may interfere with the assessments of safety or efficacy or would, in the judgment of the investigator, represent a surgical risk to the subject. - Values of coagulation parameters including platelet count, normalized prothrombin complex (PK-INR), activated partial thromboplastin time (APTT) within normal ranges. - The subject is medically able to undergo the surgery required for stereotactic implantation of the catheter and infusion pump. - Has been given written and verbal information, has had opportunity 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Atypical form of PD including repeated head trauma, drug- or toxin-induced PD, and other neurological conditions including Shy-Drager syndrome (multiple system atrophy), progressive supranuclear palsy, Wilson's disease, Huntington's disease, Hallervorden-Spatz syndrome, Alzheimer's disease, Creutzfeldt-Jakob disease, olivopontocerebellar atrophy, and post-traumatic encephalopathy - Concurrent dementia with a score of 20 or lower on the MMT rating scale - Concurrent clinically significant depression with a score of 16 or higher on the MADRS rating scale, equivalent to moderate or severe depression. - Exposure to neuroleptic drugs blocking dopamine receptors within 6 months - History of structural brain disease including tumors and hyperplasia - History of increased intracranial pressure - Prior surgical procedures or implantation of device for the treatment of PD - Prior exposure to any formulation of PDGF-BB (including topical) - Uncontrolled hypertension with blood pressure >160 mmHg systolic or >90 mmHg diastolic. - Any disorder that precludes a surgical procedure (eg, signs of sepsis or inadequately treated infection), alters wound healing (e.g. including bleeding disorders), or renders chronic ICV delivery or device implants medically unsuitable. - Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally. Physicians should specifically investigate anatomical factors at or near the implant site (e.g., vascular abnormalities, neoplasms, or other abnormalities), underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., hemophilia, Von Willebrand's disease, liver disease, or other medical conditions), and the administration of any antiplatelet or anticoagulant medication (e.g., aspirin, Plavix, NSAIDs) in the pre- or perioperative period. Any of those conditions or drugs could place a patient at an increased risk for intraoperative or postoperative bleeding. - Presence of an implanted shunt for the drainage of cerebrospinal fluid (CSF) or an implanted central nervous system (CNS) catheter. - Presence of cardiac pacemakers, spinal cord stimulators, implantable programmable intraspinal drug pumps, or any other device that may interfere or interact with the programmer, without prior approval by Medtronic. - Clinically significant abnormalities in hematology or clinical chemistry parameters as assessed by the investigator - Ongoing medical condition that according to the investigator would interfere with the conduct and assessments in the study. Examples are medical disability (eg, severe degenerative arthritis, compromised nutritional state, peripheral neuropathy) that would interfere with the assessment of safety and efficacy of investigational product or device performance, or would compromise the ability of the subject to undergo study procedures (eg, MRI, PET), or to give informed consent. - Participation in another clinical trial with an investigational drug or device within 3 months prior to Screening visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of intracerebroventricular (ICV) administration of sNN0031 to patients with Parkinson?s disease (PD), using an implanted catheter and a Synchromed II pump, through assessment of: - ECGs, vital signs and clinical laboratory tests - Adverse events (AEs) and withdrawals related to AEs - Possible pathological changes in the brain, spinal cord or retina identified through MRI, funduscopy and assessment of visual acuity and perimetry - Possible signs of intracranial bleeding or loss of blood-brain-barrier integrity through measurements of bilirubin and albumin levels in CSF collected through lumbar puncture - Device performance as characterized by catheter tip placement (MRI) and infusion accuracy (pump residual volume);Secondary Objective: To explore the effect of ICV administration of sNN0031 on the time course of PD related parameters including: - Disease activity as measured by UPDRS including videotaping - Concurrent pharmacological treatment for PD - Depressive signs and symptoms as measured by MADRS - Cognition/dementia as measured by MMT - Quality of life as measured by the EQ-5D rating scale - To assess changes in caudate and putamen dopamine turnover using PET scans of 18F-dopa uptake - To explore the levels of PDGF-BB in CSF collected through lumbar puncture;Primary end point(s): - ECGs, vital signs and clinical laboratory tests - Adverse events (AEs) and withdrawals related to AEs - Possible pathological changes in the brain, spinal cord or retina identified through MRI, funduscopy and assessment of visual acuity and perimetry - Possible signs of intracranial bleeding or loss of blood-brain-barrier integrity through measurements of bilirubin and albumin levels in CSF collected through lumbar puncture - Device performance as characterized by catheter tip placement (MRI) and infusion accuracy (pump residual volume) | — |
Countries
Sweden
Outcome results
None listed