Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01999803
Recruitment Status : Terminated (Issues with development and supply of infusion system for delivery of IMP. Lack of favorable benefit risk ratio in sNN0029-003 study (review of interim data).)
First Posted : December 3, 2013
Last Update Posted : January 27, 2016
Sponsor:
Information provided by (Responsible Party):
Newron Sweden AB

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).

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: sNN0029 Drug: Placebo Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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 Start Date : September 2014
Actual Primary Completion Date : October 2015
Actual Study Completion Date : October 2015


Arm Intervention/treatment
Experimental: sNN0029 (VEGF)
4 µg/d of sNN0029 administered by continuous intracerebral infusion during12 weeks
Drug: sNN0029
Other Name: telbermin, rhVEGF165

Placebo Comparator: Placebo
Placebo administered by continuous intracerebral infusion during12 weeks
Drug: Placebo
Other Name: Artificial CSF




Primary Outcome Measures :
  1. Number of Adverse Events (AEs) [ Time Frame: 12 weeks ]
    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.


Secondary Outcome Measures :
  1. VEGF165 levels in Cerebrospinal Fluid (CSF) [ Time Frame: 12 weeks ]
    Levels of the active ingredient of sNN0029 infusion solution (VEGF165) in CSF will be summarised using descriptive statistics by time point and treatment.

  2. Medical Device performance [ Time Frame: 12 weeks ]
    Device performance (number of values +/-25% of expected) will be presented by time point and treatment.


Other Outcome Measures:
  1. ALS Functional Raring Scale - Revised (ALSFRS-R) [ Time Frame: 12 weeks ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

  1. Impaired respiratory function judged to pose a risk to the patient during anaesthesia for the device implantation.
  2. Hypertension defined as blood pressure >160 mmHg systolic or >90 mmHg diastolic.
  3. Values for coagulation parameters including platelet count, normalised prothrombin complex (PK-INR), activated partial thromboplastin time (APTT) outside normal ranges.
  4. Ophthalmological examination (fundus photography, visual acuity and perimetry) with any clinically significant findings that imply safety concerns for this study.
  5. Diagnosis of diabetes mellitus.
  6. History of structural brain disease other than ALS, including tumours and hyperplasia.
  7. 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.
  8. 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.
  9. 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

  10. 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.
  11. Presence of additional risk factors for thromboembolism such as obesity (BMI > 35) or use of oestrogens including combined contraceptive pills.
  12. Presence of an implanted shunt for the drainage of CSF or an implanted Central Nervous System (CNS) catheter.
  13. Clinically significant abnormalities in haematology or clinical chemistry parameters as assessed by the investigator.
  14. Serological evidence of Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Human immunodeficiency virus (HIV)
  15. 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.
  16. Participation in another clinical trial with an investigational drug or device within 3 months prior to screening visit.
  17. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01999803


Locations
Layout table for location information
Belgium
Philip Van Damme
Leuven, Belgium, B-3000
Netherlands
Leonard van den Berg
Utrecht, Netherlands, NL-3508
Sponsors and Collaborators
Newron Sweden AB
Investigators
Layout table for investigator information
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

Layout table for additonal information
Responsible Party: Newron Sweden AB
ClinicalTrials.gov Identifier: NCT01999803     History of Changes
Other Study ID Numbers: sNN0029-003
2012-001026-10 ( EudraCT Number )
First Posted: December 3, 2013    Key Record Dates
Last Update Posted: January 27, 2016
Last Verified: January 2016

Additional relevant MeSH terms:
Layout table for MeSH terms
Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases