- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01999803
A Safety Study of sNN0029 Administration Via Intracerebroventricular Route to Patients With ALS
A Phase I, Randomised, Double-blind, Placebo-controlled Study in Patients With Amyotrophic Lateral Sclerosis to Further Assess the Safety and Tolerability of Intracerebroventricular Administration of sNN0029 Infusion Solution
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Leuven, Belgium, B-3000
- Philip Van Damme
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Utrecht, Netherlands, NL-3508
- Leonard van den Berg
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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)
- 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 patient 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.
For women only: pregnant, breast feeding and/or for fecund women unwillingness to use adequate contraception during the trial such as:
- Established use of oral, injected or implanted hormonal methods of contraception that do NOT contain oestrogens.
- Placement of an intrauterine device.
- Barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: sNN0029 (VEGF)
4 µg/d of sNN0029 administered by continuous intracerebral infusion during12 weeks
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Other Names:
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PLACEBO_COMPARATOR: Placebo
Placebo administered by continuous intracerebral infusion during12 weeks
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Adverse Events (AEs)
Time Frame: 12 weeks
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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.
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12 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
VEGF165 levels in Cerebrospinal Fluid (CSF)
Time Frame: 12 weeks
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Levels of the active ingredient of sNN0029 infusion solution (VEGF165) in CSF will be summarised using descriptive statistics by time point and treatment.
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12 weeks
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Medical Device performance
Time Frame: 12 weeks
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Device performance (number of values +/-25% of expected) will be presented by time point and treatment.
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12 weeks
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
ALS Functional Raring Scale - Revised (ALSFRS-R)
Time Frame: 12 weeks
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ALSFRS-R score (0=worst to 48=best) will be analysed as absolute value and as change from baseline using descriptive statistics by time point and treatment.
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12 weeks
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: 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
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- sNN0029-003
- 2012-001026-10 (EUDRACT_NUMBER)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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