NISCI - Nogo Inhibition in Spinal Cord Injury

Study Overview
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Brief Summary
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The purpose of the NISCI trial is to test if an antibody therapy can improve movement and quality of life of tetraplegic patients. A previous trial showed this treatment is safe and well accepted. This is a placebo controlled, randomized, double blind, multicenter, multinational study to assess the safety, tolerability, feasibility and preliminary efficacy of early (within 4-28 days post injury) initiation of treatment with repeated bolus injections of NG-101 in cervical acute SCI patients. The study has 3 phases: screening/baseline Phase, treatment phase, and a follow-up phase. The study design will allow simultaneous enrolment of patients with complete or incomplete SCI. Enrolment and stratification of the patients is based and individualized prediction of upper limb outcomes. For further information please visit NISCI website: https://nisci-2020.eu

Official Title
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Antibodies Against Nogo-A to Enhance Plasticity, Regeneration and Functional Recovery After Spinal Cord Injury - A Multicenter International Randomized Double Blind Placebo Controlled Phase II Clinical Proof of Concept Trial

Conditions
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Spinal Cord Injury, Acute

Intervention / Treatment
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* Drug: NG-101
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute cervical spinal cord injury (SCI) (Neurological level of injury C1-C8 with confirmed classification of ASIA impairment scale (AIS) A-D at screening and predicted upper extremities motor score (UEMS) recovery of less than 41/50 (according to the URP prediction model) 4-28 days post-injury No required mechanical ventilation or patients that not completely depend on mechanical ventilation Hemodynamically and clinical stable patient according to the acute SCI condition at baseline Written informed consent Cooperation and willingness to complete all aspects of the study Ability of subject to understand character and individual consequences of the study Exclusion Criteria: Complete anatomical transection confirmed by magnetic resonance imaging (MRI) Trauma caused by ballistic or other injury that directly penetrates the spinal cord including gunshot and knife wounds Major brachial or lumbar plexus damage/trauma Significant head trauma or other injury that was, in the opinion of the investigator, sufficient to interfere with the assessment of the spinal cord function Other significant pre-existing or current severe systemic disease such as lung, liver (exception: history of uncomplicated Hepatitis A), gastorintestinal, cardiac, immunodeficiency (including anamnestic known HIV) or kidney disease; or active malignancy History of or an acute episode of Guillain-Barre syndrome History of recent (6 months) meningitis or meningoencephalitis History of refractory epilepsy History of or current autoimmune disease Patients with uncontrolled bleeding diathesis and/or who require concomitant treatment with coumarin anticoagulant Presence of any unstable medical or psychiatric condition Drug dependence any time during the 6 month's preceding study entry Pregnant or nursing women History of a life-threatening allergic or immune mediated reaction Patients with the presence of infection around the location where the spinal needle insertions are planned for applying the intrathecal injections Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulations Patients who are unconscious History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Patients with acute cervical spinal cord injury: NG-101<br> | Drug: NG-101<br>* 6 intrathecal bolus injections, each of 45mg<br>|
| Placebo Comparator: Patients with acute cervical spinal cord injury: Placebo<br> | Drug: Placebos<br>* 6 intrathecal bolus injections, each of 45mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of upper extremity motor scores (UEMS) according to the International Standards for the Neurological Classification of Spinal Cord Injury |  | Change from screening at day 168 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of effect on motor and sensory function according to the ISNCSCI protocol |  | Change from screening at day 168 | 
| Change of effect on autonomic dysfunction measured by bladder diary |  | Change from screening at day 168 | 
| Change of effect on quality life of patients with neuro-urological disorders as measured by Qualiveen questionnaire |  | Change from screening at day 168 | 
| Change of effect on autonomic dysfunction as measured by bladder function assessment |  | Change from screening at day 168 | 
| Change of effect on functioning, evaluated by the Spinal Cord Independence Measure (SCIM-III) |  | Change from baseline at day 168 | 
| Change of effect on hand/upper limb function as assessed by the Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) |  | Change from baseline at day 168 | 
| Change of effect on the Walking Index for Spinal Cord Injury (WISCI |  | Change from baseline at day 168 | 
| Change of effect on 10 meter walk test (10mWT) |  | Change from baseline at day 168 | 
| Change of effect on 6-minute walking test (6MWT) |  | Change from baseline at day 168 | 
| Change of effects on nerve conducting velocity |  | Change from screening at day 168 | 
| Change of effects on somatosensory evoked potentials |  | Change from screening at day 168 | 
| Evaluation of concentration NG-101 in serum (pharmacokinetics) |  | Change from day 0 at day 84 | 
| Evaluation of concentration NG-101 in CSF (pharmacokinetics) |  | Change from day 0 at day 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tetraplegia, Trauma, Upper limbs function