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

NCT02408562 | Terminated Phase 1 DMC

• 1 other identifier: sNN0031-004
• Study Type: interventional
• Target: 1
• Locations: 3 countries
• Sites: 5

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.

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Peak concentrations of sNN0031 in cerebrospinal fluid during two 14 day continuous infusion cycles

  14 days x 2

• Pump flow error rate

  10 months

• Number of patients with AEs related to the Implanted Infusion System

  10 months

Other Outcomes (12)

• Explorative evaluation of changes to the Modified Hoehn &Yahr stage following two cycles of sNN0031

  10 monhts

• Explorative evaluation of changes to the Unified Parkinson's disease rating scale (UPDRS) following two cycles of sNN0031

  10 monhts

• Explorative evaluation of changes to the Parkinson's disease questionnaire (PDQ-39) following two cycles of sNN0031

  10 monhts

Study Arms (2)

sNN0031

EXPERIMENTAL

sNN0031 Infusion Solution (in aCSF) for intracerebroventricular (i.c.v.) administration by an implanted infusion pump

Other: i.c.v. infusion of sNN0031 by an Implanted infusion system

Placebo

PLACEBO COMPARATOR

Articifial Cerebro Spinal Fluid (aCSF) for intracerebroventricular (i.c.v.) administration by an implanted infusion pump

Other: i.c.v. infusion of aCSF by an Implanted infusion system

Interventions

i.c.v. infusion of sNN0031 by an Implanted infusion system OTHER

I.c.v. infusion during 2 12d cycles separated by 3 mo. 6 mo follow-up after 2nd cycle.

Also known as: rhPDGF-BB, Medtronic SynchroMed® II Infusion System

sNN0031

i.c.v. infusion of aCSF by an Implanted infusion system OTHER

I.c.v. infusion during 2 12d cycles separated by 3 mo. 6 mo follow-up after 2nd cycle.

Also known as: Placebo, Artificial Cerebrospinal fluid, Medtronic SynchroMed® II Infusion System

Placebo

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Disease duration ≥ 5 years (diagnosis based on medical history and neurological examination).
• Male or female, age 30 - 75 years inclusive.
• Motor fluctuations, with OFF-time \>1.5 hours during the day
• A Hoehn and Yahr stage of 2 to 4 during OFF phase
• Score \>22 on the UPDRS part III during ON phase
• 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)
• Optimised and stable anti-Parkinson treatment for at least 3 months before screening

You may not qualify if:

• The patient has any indication of forms of parkinsonism other than idiopathic Parkinson's disease
• 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
• Patients who are on treatment with Duodopa or Apomorphine pump at the time of screening
• 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
• Concurrent diagnoses of dementia with a score of 24 or lower on Mini-Mental State Examination (MMSE).
• The patient is depressed, as indicated by a Hamilton Depression Rating Scale (GRID-HAMD, 17-item scale) score \> 17
• Patients who are at high risk of suicide as judged by the rating of the Columbia Symptoms Suicide Rating Scale (C-SSRS)
• Patients with a history of increased intracranial pressure
• 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
• The patient has a current clinically significant gastrointestinal, renal, hepatic, endocrine, pulmonary or cardiovascular disease
• The patient has heart problems or a significant ECG abnormality
• Uncontrolled hypertension.
• The patient has in the past experienced psychotic symptoms (e.g. schizophrenia or psychotic depression)
• The patient has a mental or physical condition which would preclude performing study assessments
• Alcohol or substance dependence within the prior 12 months, or abuse within 3 months, with the exceptions of nicotine

Sponsors & Collaborators

• Newron Sweden AB: lead
• European Union: collaborator

Study Sites (5)

Klinikum-Bremerhaven

Bremerhaven, DE-27574, Germany

Location

Lund University Hospital

Lund, 22185, Sweden

Location

Karolinska University Hospital Huddinge

Stockholm, 141 86, Sweden

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Becaplermin

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Proto-Oncogene Proteins c-sis; Platelet-Derived Growth Factor; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; DNA-Binding Proteins; Proteins; Biological Factors

Study Officials

• Håkan Widner, Prof

  Lund University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2015
• First Posted: April 3, 2015
• Study Start: January 1, 2015
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: January 27, 2016

Record last verified: 2016-01

Locations

DE (1); GB (2); SE (2)