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

NCT ID: NCT01999803

Last Updated: 2016-01-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2015-10-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

sNN0029 (VEGF)

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

Group Type: EXPERIMENTAL

sNN0029

Intervention Type: DRUG

Placebo

Placebo administered by continuous intracerebral infusion during12 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

sNN0029

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

telbermin, rhVEGF165; Artificial CSF

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Newron Sweden AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philip VanDamme, Prof, MD

Role: PRINCIPAL_INVESTIGATOR

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

Leonard van den Berg, MD, Prof

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Philip Van Damme

Leuven, , Belgium

Leonard van den Berg

Utrecht, , Netherlands

Countries

Belgium; Netherlands

Other Identifiers

2012-001026-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

sNN0029-003

Identifier Type: -

Identifier Source: org_study_id