NISCI - Nogo Inhibition in Spinal Cord Injury

NCT03935321 | Completed Phase 2 DMC

• 1 other identifier: EudraCT No. 2016-001227-31
• Study Type: interventional
• Target: 129
• Locations: 4 countries
• Sites: 13

Brief Summary

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

Conditions

Spinal Cord Injury, Acute

Keywords

Tetraplegia; Trauma; Upper limbs function

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• 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

Study Arms (2)

Patients with acute cervical spinal cord injury: NG-101

ACTIVE COMPARATOR

Drug: NG-101

Patients with acute cervical spinal cord injury: Placebo

PLACEBO COMPARATOR

Drug: Placebos

Interventions

NG-101 DRUG

6 intrathecal bolus injections, each of 45mg

Patients with acute cervical spinal cord injury: NG-101

Placebos DRUG

6 intrathecal bolus injections, each of 45mg

Patients with acute cervical spinal cord injury: Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Zurich: lead
• EMSCI.org: collaborator
• State Secretariat for Education Research and Innovation, Switzerland: collaborator
• Horizon 2020 - European Commission: collaborator
• Foundation Wings For Life: collaborator
• Swiss Paraplegic Research, Nottwil: collaborator
• Heidelberg University Hospital Spinal Cord Injury Center: collaborator
• KKS Netzwerk: collaborator

Study Sites (13)

Spinal Cord Unit, University Hospital Motol

Prague, Czechia

Location

Klinik für Querschnittgelähmte, Klinikum Bayreuth

Bayreuth, Germany

Location

Behandlungszentrum für Rückenmarkverletzte, Unfallkrankenhaus Berlin

Berlin, Germany

Location

Abteilung für Rückenmarkverletzte, BG Universitätsklinikum Bergmannsheil gGmbH

Bochum, Germany

Location

Zentrum für Rückenmarkverletzte und Klinik für Orthopädie, BG Klinikum Bergmannstrost

Halle, Germany

Location

Klinik für Paraplegiologie, Universitätsklinikum Heidelberg

Heidelberg, Germany

Location

Zentrum für Tetra- und Paraplegie, Orthopädische Klinik Hessisch Lichtenau gGmbH

Hessisch Lichtenau, Germany

Location

Zentrum für Rückenmarksverletzte, Unfallklinik Murnau

Murnau am Staffelsee, Germany

Location

BG Klinik Tübingen

Tübingen, Germany

Location

Center for Neurorehabilitation, Fundacio Institut Guttmann

Barcelona, Spain

Location

Rehab Basel

Basel, Switzerland

Location

Schweizer Paraplegikerzentrum

Nottwil, Switzerland

Location

Universitätsklinik Balgrist

Zurich, 8008, Switzerland

Location

Related Publications (3)

• 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.

  PMID: 29869587 BACKGROUND

• Giagiozis M, Lerch I, Linke AD, Jutzeler CR, Rupp R, Abel R, Benito-Penalva J, Waldmann J, Maier D, Baumberger M, Kriz J, Badke A, Hund-Georgiadis M, Weidner N, Demko L, Curt A. Feasibility and Sensitivity of Wearable Sensors for Daily Activity Monitoring in Spinal Cord Injury Trials. Neurorehabil Neural Repair. 2025 Oct;39(10):814-825. doi: 10.1177/15459683251352556. Epub 2025 Jul 10.

  PMID: 40637209 DERIVED

• Weidner N, Abel R, Maier D, Rohl K, Rohrich F, Baumberger M, Hund-Georgiadis M, Saur M, Benito J, Rehahn K, Aach M, Badke A, Kriz J, Barkovits K, Killeen T, Farner L, Seif M, Hubli M, Marcus K, Maurer MA, Robert B, Rupp R, Scheuren PS, Schubert M, Schuld C, Sina C, Steiner B, Weis T, Hug A, Bolliger M, Weiskopf N, Freund P, Hothorn T, Schwab ME, Curt A; Nogo Inhibition in Spinal Cord Injury Study Group. Safety and efficacy of intrathecal antibodies to Nogo-A in patients with acute cervical spinal cord injury: a randomised, double-blind, multicentre, placebo-controlled, phase 2b trial. Lancet Neurol. 2025 Jan;24(1):42-53. doi: 10.1016/S1474-4422(24)00447-2.

  PMID: 39706632 DERIVED

MeSH Terms

Conditions

Spinal Cord Injuries; Quadriplegia; Wounds and Injuries

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Armin Curt, Prof.

  Universität Zürich / University Hospital Balgrist

  PRINCIPAL INVESTIGATOR

• Norbert Weidner, Prof.

  University Hospital Heidelberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2019
• First Posted: May 2, 2019
• Study Start: May 15, 2019
• Primary Completion: February 2, 2023
• Study Completion: February 2, 2023
• Last Updated: April 4, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (8); CZ (1); CH (3); ES (1)