Parkinson's Disease
Conditions
Brief summary
This is a phase I, randomised, placebo-controlled study to assess the safety and tolerability of two 2-weeks cycles of i.c.v. administration of sNN0031 infusion solution to patients with PD of moderate severity with persisting on-off symptoms in spite of other PD medications.
Interventions
OTHERi.c.v. infusion of sNN0031 by an Implanted infusion system
I.c.v. infusion during 2 12d cycles separated by 3 mo. 6 mo follow-up after 2nd cycle.
OTHERi.c.v. infusion of aCSF by an Implanted infusion system
I.c.v. infusion during 2 12d cycles separated by 3 mo. 6 mo follow-up after 2nd cycle.
Sponsors
European Union
Newron Sweden AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: 1. Disease duration ≥ 5 years (diagnosis based on medical history and neurological examination). 2. Male or female, age 30 - 75 years inclusive. 3. Motor fluctuations, with OFF-time \>1.5 hours during the day 4. A Hoehn and Yahr stage of 2 to 4 during OFF phase 5. Score \>22 on the UPDRS part III during ON phase 6. Patients should be L-dopa responsive and demonstrate at least a 30% decrease in the UPDRS part III score after administration of L-dopa (L-dopa challenge test) 7. Optimised and stable anti-Parkinson treatment for at least 3 months before screening Main
Exclusion criteria
1. The patient has any indication of forms of parkinsonism other than idiopathic Parkinson's disease 2. The patient is in a late stage of Parkinson's disease, and is experiencing severe, disabling peak-dose or biphasic dyskinesia and/or unpredictable or widely swinging fluctuations in their symptoms 3. Patients who are on treatment with Duodopa or Apomorphine pump at the time of screening 4. The patient has an implanted shunt for the drainage of CSF or an implanted Central Nervous System (CNS) catheter, or have received neurosurgical intervention related to PD (e.g. deep brain stimulation, thalamotomy etc.) or is scheduled to do so during the trial period 5. Concurrent diagnoses of dementia with a score of 24 or lower on Mini-Mental State Examination (MMSE). 6. The patient is depressed, as indicated by a Hamilton Depression Rating Scale (GRID-HAMD, 17-item scale) score \> 17 7. Patients who are at high risk of suicide as judged by the rating of the Columbia Symptoms Suicide Rating Scale (C-SSRS) 8. Patients with a history of increased intracranial pressure 9. Ophthalmologic examination (funduscopy and visual acuity by Early Treatment of Diabetic Retinopathy Study (EDTRS) and perimetry) with clinically significant findings that imply safety concerns for this study 10. The patient has a current clinically significant gastrointestinal, renal, hepatic, endocrine, pulmonary or cardiovascular disease 11. The patient has heart problems or a significant ECG abnormality 12. Uncontrolled hypertension. 13. The patient has in the past experienced psychotic symptoms (e.g. schizophrenia or psychotic depression) 14. The patient has a mental or physical condition which would preclude performing study assessments 15. Alcohol or substance dependence within the prior 12 months, or abuse within 3 months, with the exceptions of nicotine 16. MRI examination with findings of tumours or potential sources of pathological bleedings, or any abnormality that may put the patient at risk 17. History of structural brain disease including tumours and hyperplasia 18. Ongoing or suspected primary or recurrent malignant disease (currently active or in remission for less than one year) 19. Any disorder that precludes a surgical procedure, alters wound healing or renders chronic i.c.v. delivery or device implants medically unsuitable 20. The patient has a history or a current diagnosis of HIV, Hepatitis B or C. 21. Increased susceptibility to infections 22. Women who are pregnant or breast feeding or unwilling to use adequate contraception during the trial (only women of child bearing potential)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability of sNN0031 [Number of Adverse Events (AE) and Serious Adverse Events (SAE) occurring in each group over the study duration] | 10 months | Number of AEs and SAEs occurring in each group over the study duration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak concentrations of sNN0031 in cerebrospinal fluid during two 14 day continuous infusion cycles | 14 days x 2 | To explore peak concentrations of Platelet Derived Growth Factor-BB (PDGF-BB) levels in cerebrospinal fluid (CSF) during two different treatment cycles of 70 μg sNN0031 each separated by 3 months |
| Pump flow error rate | 10 months | Performance of the Medtronic SynchroMed® II Infusion System - Pump flow error rate within 25% |
| Number of patients with AEs related to the Implanted Infusion System | 10 months | Number of AEs and SAEs related to the Medtronic SynchroMed® II Infusion System occurring in each group over the study duration |
Other
| Measure | Time frame | Description |
|---|---|---|
| Explorative evaluation of changes to the o Non-motor symptom scale (NMSS 30) following two cycles of sNN0031 | 10 monhts | To explore the change from baseline in relevant efficacy related variables: o Non-motor symptom scale (NMSS 30) |
| Changes in presynaptic dopamine transporter (DAT) binding | 10 months | To explore changes in presynaptic dopamine transporter (DAT) binding in basal ganglia by using DaTscan |
| Explorative evaluation of potentially relevant biomarkers (inflammatory mediators) in plasma and CSF during and after two cycles of sNN0031 | 10 months | To explore potentially relevant biomarkers in plasma and CSF - inflammatory mediators. |
| Explorative evaluation of potentially relevant biomarkers (urate) in plasma and CSF during and after two cycles of sNN0031 | 10 months | To explore potentially relevant biomarkers in plasma and CSF - urate. |
| Explorative evaluation of changes to the Modified Hoehn &Yahr stage following two cycles of sNN0031 | 10 monhts | To explore the change from baseline in relevant efficacy related variables: o Modified Hoehn &Yahr stage |
| Explorative evaluation of potentially relevant biomarkers (alpha-synuclein) in plasma and CSF during and after two cycles of sNN0031 | 10 months | To explore potentially relevant biomarkers in plasma and CSF - alpha-synuclein. |
| Explorative evaluation of potentially relevant biomarkers (haemoglobin) in plasma and CSF during and after two cycles of sNN0031 | 10 months | To explore potentially relevant biomarkers in plasma and CSF - haemoglobin. |
| Explorative evaluation of potentially relevant biomarkers (nitrite/nitrate) in plasma and CSF during and after two cycles of sNN0031 | 10 months | To explore potentially relevant biomarkers in plasma and CSF - nitrite/nitrate. |
| Explorative evaluation of potentially relevant biomarkers (DJ-1/Park7) in plasma and CSF during and after two cycles of sNN0031 | 10 months | To explore potentially relevant biomarkers in plasma and CSF - DJ-1/Park7. |
| Explorative evaluation of changes to the Unified Parkinson's disease rating scale (UPDRS) following two cycles of sNN0031 | 10 monhts | To explore the change from baseline in relevant efficacy related variables: o Unified Parkinson's disease rating scale (UPDRS) |
| Explorative evaluation of changes to the Parkinson's disease questionnaire (PDQ-39) following two cycles of sNN0031 | 10 monhts | To explore the change from baseline in relevant efficacy related variables: o Parkinson's disease questionnaire (PDQ-39) |
| Explorative evaluation of changes to the Dyskinesia rating scale (DRS) following two cycles of sNN0031 | 10 monhts | To explore the change from baseline in relevant efficacy related variables: o Dyskinesia rating scale (DRS) |
Countries
Germany, Sweden, United Kingdom
Outcome results
None listed