A Safety Study of sNN0029 Administration Via Intracerebroventricular Route to Patients With ALS

NCT01999803 | Terminated Phase 1 DMC

• 2 other identifiers: sNN0029-0032012-001026-10
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a phase I, multicentre randomised, double-blind, placebo-controlled trial to assess the safety and tolerability of continuous i.c.v. administration of sNN0029 infusion solution at a dose of 4µg/day in patients with Amyotrophic Lateral Sclerosis (ALS).

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events (AEs)

  The safety and tolerability of i.c.v. administration of sNN0029 infusion solution at a dose of 4 µg/day delivered via a Medtronic SynchroMed® II Infusion System will be evaluated by comparing tabulated number of events over 12 weeks by body system, preferred term and by severity and relationship to study medication/device. Serious Adverse Events/Serious Adverse Device Events will also be presented in separate tabulations.

  12 weeks

Secondary Outcomes (2)

• VEGF165 levels in Cerebrospinal Fluid (CSF)

  12 weeks

• Medical Device performance

  12 weeks

Other Outcomes (1)

• ALS Functional Raring Scale - Revised (ALSFRS-R)

  12 weeks

Study Arms (2)

sNN0029 (VEGF)

EXPERIMENTAL

4 µg/d of sNN0029 administered by continuous intracerebral infusion during12 weeks

Drug: sNN0029

Placebo

PLACEBO COMPARATOR

Placebo administered by continuous intracerebral infusion during12 weeks

Drug: Placebo

Interventions

sNN0029 DRUG

Also known as: telbermin, rhVEGF165

sNN0029 (VEGF)

Placebo DRUG

Also known as: Artificial CSF

Placebo

Eligibility Criteria

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

You may qualify if:

• Clinical diagnosis of ALS classified as definite, or probable with or without additional laboratory evidence, according to the revised World Federation of Neurology (WFN) El Escorial criteria.
• If patients are being treated with riluzole, they must have been on a stable dose for at least the past 30 days prior to screening.
• The patient is, in the opinion of the investigator, medically fit to undergo the surgery required for stereotactic implantation of the catheter and infusion pump.

You may not qualify if:

• Impaired respiratory function judged to pose a risk to the patient during anaesthesia for the device implantation.
• Hypertension defined as blood pressure \>160 mmHg systolic or \>90 mmHg diastolic.
• Values for coagulation parameters including platelet count, normalised prothrombin complex (PK-INR), activated partial thromboplastin time (APTT) outside normal ranges.
• Ophthalmological examination (fundus photography, visual acuity and perimetry) with any clinically significant findings that imply safety concerns for this study.
• Diagnosis of diabetes mellitus.
• History of structural brain disease other than ALS, including tumours and hyperplasia.
• An MRI of the brain and cervical spine, and an Magnetic Resonance Angiography (MRA) of the brain with findings of tumours or potential sources of pathological bleedings, or abnormality that may interfere with the assessments of safety or efficacy or that would, in the judgment of the investigator, represent a surgical risk to the patient. If an MRI and/or MRA has been performed within 1 month prior to screening, the results from that examination can be used.
• Any disorder that precludes a surgical procedure (e.g., signs of sepsis or inadequately treated infection), alters wound healing (e.g., including bleeding disorders), or renders chronic i.c.v. delivery or device implants medically unsuitable.
• Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that cannot be not managed optimally due to:
• i. anatomical factors at or near the implant site (e.g., vascular abnormalities, neoplasms, or other abnormalities), ii. underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., haemophilia, Von Willebrand's disease, liver disease, or other medical conditions) iii. administration of any antiplatelet or anticoagulant medication in the preoperative period
• A personal history of thromboembolic disease. A family history of thromboembolic disease will prompt a laboratory assessment to exclude hereditary liability before the patient is declared eligible.
• Presence of additional risk factors for thromboembolism such as obesity (BMI \> 35) or use of oestrogens including combined contraceptive pills.
• Presence of an implanted shunt for the drainage of CSF or an implanted Central Nervous System (CNS) catheter.
• Clinically significant abnormalities in haematology or clinical chemistry parameters as assessed by the investigator.
• Serological evidence of Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Human immunodeficiency virus (HIV)

Sponsors & Collaborators

• Newron Sweden AB: lead

Study Sites (2)

Philip Van Damme

Leuven, B-3000, Belgium

Location

Leonard van den Berg

Utrecht, NL-3508, Netherlands

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Philip VanDamme, Prof, MD

  University Hospital Leuven, Herestraat 49, B-3000 Leuven, Belgium

  PRINCIPAL INVESTIGATOR

• Leonard van den Berg, MD, Prof

  University Medical Center Utrecht, Department of Neurology G03.228, P.O. Box 85500, NL-3508 GA Utrecht, The Netherlands

  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: November 22, 2013
• First Posted: December 3, 2013
• Study Start: September 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: January 27, 2016

Record last verified: 2016-01

Locations

BE (1); NL (1)