NISCI - Nogo Inhibition in Spinal Cord Injury (NISCI)

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

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

Study Overview

• Status: Completed
• Conditions: Spinal Cord Injury, Acute
• Intervention / Treatment: Drug: NG-101; Drug: Placebos

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Praha, Czechia
    • Spinal Cord Unit, University Hospital Motol
• Germany
  • Bayreuth, Germany
    • Klinik für Querschnittgelähmte, Klinikum Bayreuth
  • Berlin, Germany
    • Behandlungszentrum für Rückenmarkverletzte, Unfallkrankenhaus Berlin
  • Bochum, Germany
    • Abteilung für Rückenmarkverletzte, BG Universitätsklinikum Bergmannsheil gGmbH
  • Halle, Germany
    • Zentrum für Rückenmarkverletzte und Klinik für Orthopädie, BG Klinikum Bergmannstrost
  • Heidelberg, Germany
    • Klinik für Paraplegiologie, Universitätsklinikum Heidelberg
  • Hessisch Lichtenau, Germany
    • Zentrum für Tetra- und Paraplegie, Orthopädische Klinik Hessisch Lichtenau gGmbH
  • Murnau Am Staffelsee, Germany
    • Zentrum für Rückenmarksverletzte, Unfallklinik Murnau
  • Tübingen, Germany
    • BG Klinik Tübingen
• Spain
  • Barcelona, Spain
    • Center for Neurorehabilitation, Fundacio Institut Guttmann
• Switzerland
  • Basel, Switzerland
    • REHAB Basel
  • Nottwil, Switzerland
    • Schweizer Paraplegikerzentrum
  • Zürich, Switzerland, 8008
    • Universitätsklinik Balgrist

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: KKS Netzwerk; Foundation Wings For Life; Horizon 2020 - European Commission; State Secretariat for Education Research and Innovation, Switzerland; Swiss Paraplegic Research; EMSCI.org; Heidelberg University Hospital Spinal Cord Injury Center
• Investigators: Principal Investigator: Armin Curt, Prof., Universität Zürich / University Hospital Balgrist; Principal Investigator: Norbert Weidner, Prof., University Hospital Heidelberg

Publications and helpful links

General Publications

• Kucher K, Johns D, Maier D, Abel R, Badke A, Baron H, Thietje R, Casha S, Meindl R, Gomez-Mancilla B, Pfister C, Rupp R, Weidner N, Mir A, Schwab ME, Curt A. First-in-Man Intrathecal Application of Neurite Growth-Promoting Anti-Nogo-A Antibodies in Acute Spinal Cord Injury. Neurorehabil Neural Repair. 2018 Jun;32(6-7):578-589. doi: 10.1177/1545968318776371. Epub 2018 Jun 5.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2019
• Primary Completion (Actual): February 2, 2023
• Study Completion (Actual): February 2, 2023

Study Registration Dates

• First Submitted: March 25, 2019
• First Submitted That Met QC Criteria: April 29, 2019
• First Posted (Actual): May 2, 2019

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Trauma; Tetraplegia; Upper limbs function
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Spinal Cord Diseases; Wounds and Injuries; Spinal Cord Injuries
• Other Study ID Numbers: EudraCT No. 2016-001227-31

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No