NISCI - Nogo Inhibition in Spinal Cord Injury

NCT ID: NCT03935321

Last Updated: 2023-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 129 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-15
• Study Completion Date: 2023-02-02

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

Study Design

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

Study Groups

Patients with acute cervical spinal cord injury: NG-101

Group Type: ACTIVE_COMPARATOR

NG-101

Intervention Type: DRUG

6 intrathecal bolus injections, each of 45mg

Patients with acute cervical spinal cord injury: Placebo

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

6 intrathecal bolus injections, each of 45mg

Interventions

NG-101

6 intrathecal bolus injections, each of 45mg

Intervention Type: DRUG

Placebos

6 intrathecal bolus injections, each of 45mg

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EMSCI.org

UNKNOWN

Sponsor Role: collaborator

State Secretariat for Education Research and Innovation, Switzerland

OTHER

Sponsor Role: collaborator

Horizon 2020 - European Commission

OTHER

Sponsor Role: collaborator

Foundation Wings For Life

OTHER

Sponsor Role: collaborator

Swiss Paraplegic Research, Nottwil

NETWORK

Sponsor Role: collaborator

Heidelberg University Hospital Spinal Cord Injury Center

UNKNOWN

Sponsor Role: collaborator

KKS Netzwerk

NETWORK

Sponsor Role: collaborator

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Armin Curt, Prof.

Role: PRINCIPAL_INVESTIGATOR

Universität Zürich / University Hospital Balgrist

Norbert Weidner, Prof.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Heidelberg

Locations

Spinal Cord Unit, University Hospital Motol

Prague, , Czechia

Klinik für Querschnittgelähmte, Klinikum Bayreuth

Bayreuth, , Germany

Behandlungszentrum für Rückenmarkverletzte, Unfallkrankenhaus Berlin

Berlin, , Germany

Abteilung für Rückenmarkverletzte, BG Universitätsklinikum Bergmannsheil gGmbH

Bochum, , Germany

Zentrum für Rückenmarkverletzte und Klinik für Orthopädie, BG Klinikum Bergmannstrost

Halle, , Germany

Klinik für Paraplegiologie, Universitätsklinikum Heidelberg

Heidelberg, , Germany

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

Hessisch Lichtenau, , Germany

Zentrum für Rückenmarksverletzte, Unfallklinik Murnau

Murnau am Staffelsee, , Germany

BG Klinik Tübingen

Tübingen, , Germany

Center for Neurorehabilitation, Fundacio Institut Guttmann

Barcelona, , Spain

Rehab Basel

Basel, , Switzerland

Schweizer Paraplegikerzentrum

Nottwil, , Switzerland

Universitätsklinik Balgrist

Zurich, , Switzerland

Countries

Czechia; Germany; Spain; Switzerland

References

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.

Reference Type: BACKGROUND

PMID: 29869587 (View on PubMed)

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 Jul 10;39(10):15459683251352556. doi: 10.1177/15459683251352556. Online ahead of print.

Reference Type: DERIVED

PMID: 40637209 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39706632 (View on PubMed)

Other Identifiers

EudraCT No. 2016-001227-31

Identifier Type: -

Identifier Source: org_study_id