Study on Tolerability of Repeat i.c.v. Administration of sNN0031 Infusion Solution in Patients With PD

Phase 1

Terminated

• Conditions: Parkinson's Disease
• Interventions: Other: i.c.v. infusion of aCSF by an Implanted infusion system; Other: i.c.v. infusion of sNN0031 by an Implanted infusion system

• Registration Number: NCT02408562
• Lead Sponsor: Newron Sweden AB

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2015-03-05
• Study First Submitted QC: 2015-03-31
• Study First Posted: 2015-04-03
• Primary Completion: 2015-10
• Study Completion: 2015-10
• Status Verified: 2016-01
• Last Update Submitted: 2016-01-26
• Last Update Posted: 2016-01-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	i.c.v. infusion of aCSF by an Implanted infusion system	Articifial Cerebro Spinal Fluid (aCSF) for intracerebroventricular (i.c.v.) administration by an implanted infusion pump
sNN0031	i.c.v. infusion of sNN0031 by an Implanted infusion system	sNN0031 Infusion Solution (in aCSF) for intracerebroventricular (i.c.v.) administration by an implanted infusion pump

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (5)

Klinikum-Bremerhaven; 🇩🇪 Bremerhaven, Germany

Lund University Hospital; 🇸🇪 Lund, Sweden

Karolinska University Hospital Huddinge; 🇸🇪 Stockholm, Sweden

King's College Hospital; 🇬🇧 London, United Kingdom

John Radcliffe Hospital; 🇬🇧 Oxford, United Kingdom