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

Parkinson's Disease Clinical Trial

Official title:

A Phase 1, Multicentre, Randomised, Double-blind Study to Assess Safety and Tolerability of Repeated Intracerebroventricular Administration of sNN0031 Infusion Solution to Patients With Parkinson's Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02408562
• Other study ID #: sNN0031-004
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: March 5, 2015
• Last updated: January 26, 2016
• Start date: January 2015
• Est. completion date: October 2015

Study information

• Verified date: January 2016
• Source: Newron Sweden AB
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products AgencyGermany: Federal Institute for Drugs and Medical DevicesUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 75 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Other:
• i.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.
• i.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.

Locations

Country	Name	City	State
Germany	Klinikum-Bremerhaven	Bremerhaven
Sweden	Lund University Hospital	Lund
Sweden	Karolinska University Hospital Huddinge	Stockholm
United Kingdom	King's College Hospital	London
United Kingdom	John Radcliffe Hospital	Oxford

Sponsors (2)

Lead Sponsor	Collaborator
Newron Sweden AB	European Union

Countries where clinical trial is conducted

Germany,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Explorative evaluation of changes to the Modified Hoehn &Yahr stage following two cycles of sNN0031	To explore the change from baseline in relevant efficacy related variables: o Modified Hoehn &Yahr stage	10 monhts	No
Other	Explorative evaluation of changes to the Unified Parkinson's disease rating scale (UPDRS) following two cycles of sNN0031	To explore the change from baseline in relevant efficacy related variables: o Unified Parkinson's disease rating scale (UPDRS)	10 monhts	No
Other	Explorative evaluation of changes to the Parkinson's disease questionnaire (PDQ-39) following two cycles of sNN0031	To explore the change from baseline in relevant efficacy related variables: o Parkinson's disease questionnaire (PDQ-39)	10 monhts	No
Other	Explorative evaluation of changes to the Dyskinesia rating scale (DRS) following two cycles of sNN0031	To explore the change from baseline in relevant efficacy related variables: o Dyskinesia rating scale (DRS)	10 monhts	No
Other	Explorative evaluation of changes to the o Non-motor symptom scale (NMSS 30) following two cycles of sNN0031	To explore the change from baseline in relevant efficacy related variables: o Non-motor symptom scale (NMSS 30)	10 monhts	No
Other	Changes in presynaptic dopamine transporter (DAT) binding	To explore changes in presynaptic dopamine transporter (DAT) binding in basal ganglia by using DaTscan	10 months	No
Other	Explorative evaluation of potentially relevant biomarkers (inflammatory mediators) in plasma and CSF during and after two cycles of sNN0031	To explore potentially relevant biomarkers in plasma and CSF - inflammatory mediators.	10 months	No
Other	Explorative evaluation of potentially relevant biomarkers (urate) in plasma and CSF during and after two cycles of sNN0031	To explore potentially relevant biomarkers in plasma and CSF - urate.	10 months	No
Other	Explorative evaluation of potentially relevant biomarkers (DJ-1/Park7) in plasma and CSF during and after two cycles of sNN0031	To explore potentially relevant biomarkers in plasma and CSF - DJ-1/Park7.	10 months	No
Other	Explorative evaluation of potentially relevant biomarkers (alpha-synuclein) in plasma and CSF during and after two cycles of sNN0031	To explore potentially relevant biomarkers in plasma and CSF - alpha-synuclein.	10 months	No
Other	Explorative evaluation of potentially relevant biomarkers (haemoglobin) in plasma and CSF during and after two cycles of sNN0031	To explore potentially relevant biomarkers in plasma and CSF - haemoglobin.	10 months	No
Other	Explorative evaluation of potentially relevant biomarkers (nitrite/nitrate) in plasma and CSF during and after two cycles of sNN0031	To explore potentially relevant biomarkers in plasma and CSF - nitrite/nitrate.	10 months	No
Primary	Tolerability of sNN0031 [Number of Adverse Events (AE) and Serious Adverse Events (SAE) occurring in each group over the study duration]	Number of AEs and SAEs occurring in each group over the study duration	10 months	Yes
Secondary	Peak concentrations of sNN0031 in cerebrospinal fluid during two 14 day continuous infusion cycles	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	14 days x 2	No
Secondary	Pump flow error rate	Performance of the Medtronic SynchroMed® II Infusion System - Pump flow error rate within 25%	10 months	Yes
Secondary	Number of patients with AEs related to the Implanted Infusion System	Number of AEs and SAEs related to the Medtronic SynchroMed® II Infusion System occurring in each group over the study duration	10 months	Yes