NISCI - Nogo Inhibition in Spinal Cord Injury

Spinal Cord Injury, Acute Clinical Trial

— NISCI  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03935321
• Other study ID #: EudraCT No. 2016-001227-31
• Status: Completed
• Phase: Phase 2
• Start date: May 15, 2019
• Est. completion date: February 2, 2023

Study information

• Verified date: April 2023
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 129
• Est. completion date: February 2, 2023
• Est. primary completion date: February 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Spinal Cord Injuries
• Spinal Cord Injury, Acute
• Wounds and Injuries

Intervention

Drug:
• NG-101
6 intrathecal bolus injections, each of 45mg
• Placebos
6 intrathecal bolus injections, each of 45mg

Locations

Country	Name	City	State
Czechia	Spinal Cord Unit, University Hospital Motol	Praha
Germany	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
Spain	Center for Neurorehabilitation, Fundacio Institut Guttmann	Barcelona
Switzerland	Rehab Basel	Basel
Switzerland	Schweizer Paraplegikerzentrum	Nottwil
Switzerland	Universitätsklinik Balgrist	Zürich

Sponsors (8)

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

Countries where clinical trial is conducted

Czechia,  Germany,  Spain,  Switzerland, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change of effect on motor and sensory function according to the ISNCSCI protocol		Change from screening at day 168
Secondary	Change of effect on autonomic dysfunction measured by bladder diary		Change from screening at day 168
Secondary	Change of effect on quality life of patients with neuro-urological disorders as measured by Qualiveen questionnaire		Change from screening at day 168
Secondary	Change of effect on autonomic dysfunction as measured by bladder function assessment		Change from screening at day 168
Secondary	Change of effect on functioning, evaluated by the Spinal Cord Independence Measure (SCIM-III)		Change from baseline at day 168
Secondary	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
Secondary	Change of effect on the Walking Index for Spinal Cord Injury (WISCI		Change from baseline at day 168
Secondary	Change of effect on 10 meter walk test (10mWT)		Change from baseline at day 168
Secondary	Change of effect on 6-minute walking test (6MWT)		Change from baseline at day 168
Secondary	Change of effects on nerve conducting velocity		Change from screening at day 168
Secondary	Change of effects on somatosensory evoked potentials		Change from screening at day 168
Secondary	Evaluation of concentration NG-101 in serum (pharmacokinetics)		Change from day 0 at day 84
Secondary	Evaluation of concentration NG-101 in CSF (pharmacokinetics)		Change from day 0 at day 84