A Safety and Tolerability Study of Intracerebroventricular Administration of sNN0029 to Patients With Amyotrophic Lateral Sclerosis

NCT00800501 | Completed Phase 1 DMC

• 1 other identifier: sNN0029-001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This study is conducted to evaluate the safety and tolerability of the drug product sNN0029, containing the growth factor VEGF165, when administered directly into one of the fluid filled cavities in the brain using an implanted catheter and an implanted SynchroMed® II pump. Patients with Amyotrophic Lateral Sclerosis will be enrolled.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; VEGF165; Safety; Intracerebroventricular; Infusion; Implantable

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability through assessment of adverse events, ECGs, vital signs, clinical laboratory variables, MRI of brain and spinal cord, CSF sampling, and device performance as characterized by catheter tip placement and infusion accuracy.

  Multiple assessments over 3 months

Secondary Outcomes (1)

• Time course of Amyotrophic Lateral Sclerosis Functional Rating Scale, Quality of life as measured by the EQ-5D rating scale

  Multiple assessments over 3 months

Study Arms (2)

sNN0029

EXPERIMENTAL

Drug: sNN0029

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

sNN0029 DRUG

Continuous ICV infusion at one of three dose levels

sNN0029

Placebo DRUG

Continuous ICV infusion

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 WFN El Escorial criteria.
• Age 18 to 75 years inclusive.
• If patients are being treated with riluzole, they must have been on a stable dose for at least 30 days.
• Ophthalmological examination at screening with normal findings regarding vascular structure and function.
• MRI/magnetic resonance angiography (MRA) examination of the brain and cervical spinal cord at screening with no findings of tumors or potential sources of pathological bleedings, or abnormality that may interfere with the assessments of safety or efficacy or that would, in the judgement of the investigator, represent a surgical risk to the subject.
• Values of coagulation parameters including platelet count, normalized prothrombin complex (PK-INR), activated partial thromboplastin time (APTT) within normal ranges.
• Patient is medically able to undergo the surgery required for stereotactic implantation of the catheter and infusion pump.
• Patient has been given written and verbal information, has had the opportunity to ask questions about the study, and understands the time and procedural commitments.
• Patient has given signed consent (written) to participate in the study. In the event that a patient who gives oral informed consent is not physically able to sign the informed consent form (ICF) due to disease progression, a witness may sign the ICF on the patient's behalf.

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.
• Diagnosis of diabetes mellitus.
• Proliferative retinopathy.
• Non-proliferative retinopathy of moderate severity or higher.
• Concurrent clinically significant dementia as determined by the investigator.
• Concurrent clinically significant depression as determined by the investigator.
• History of structural brain disease other than ALS, including tumours and hyperplasia.
• 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 ICV delivery or device implants medically unsuitable.
• Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally. Physicians should specifically investigate anatomical factors at or near the implant site (e.g., vascular abnormalities, neoplasms, or other abnormalities), underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., haemophilia, Von Willebrand's disease, liver disease, or other medical conditions), and the administration of any antiplatelet or anticoagulant medication (e.g., aspirin, Plavix, NSAIDs) in the pre- or perioperative period. Any of those conditions or drugs could place a patient at an increased risk for intraoperative or postoperative bleeding.
• Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter.
• Presence of cardiac pacemakers, spinal cord stimulators, implantable programmable intraspinal drug pumps, or any other device that may interfere or interact with the programmer, without prior approval by Medtronic.
• Clinically significant abnormalities in hematology or clinical chemistry parameters as assessed by the investigator.
• Ongoing medical condition that according to the investigator would interfere with the conduct and assessments in the study. Examples are medical disability (e.g., severe degenerative arthritis, compromised nutritional state, peripheral neuropathy) that would interfere with the assessment of safety and efficacy of investigational product or device performance, or would compromise the ability of the subject to undergo study procedures (e.g., MRI), or to give informed consent.
• Participation in another clinical trial with an investigational drug or device within 3 months prior to Screening visit.

Sponsors & Collaborators

• Newron Sweden AB: lead
• Medtronic: collaborator
• ICON Clinical Research: collaborator

Study Sites (1)

University Hospital Leuven, Department of Neurology

Leuven, 3000, Belgium

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

• Wim Robberecht, MD PhD

  University Hospital Leuven, Department of Neurology

  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 29, 2008
• First Posted: December 2, 2008
• Study Start: December 1, 2008
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: December 6, 2011

Record last verified: 2011-12

Locations

BE (1)