Clinical trial NCT03935321: NISCI - Nogo Inhibition in Spinal Cord Injury
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Spinal Cord Injury, Acute
Keywords: Tetraplegia
Trauma
Upper limbs function
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: EMSCI.org
name: State Secretariat for Education Research and Innovation, Switzerland
name: Horizon 2020 - European Commission
name: Foundation Wings For Life
name: Swiss Paraplegic Research, Nottwil
name: Heidelberg University Hospital Spinal Cord Injury Center
name: KKS Netzwerk
First posted: 2019-05-02
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Change of upper extremity motor scores (UEMS) according to the International Standards for the Neurological Classification of Spinal Cord Injury
timeFrame: Change from screening at day 168
Secondary outcomes:
measure: Change of effect on motor and sensory function according to the ISNCSCI protocol
timeFrame: Change from screening at day 168
measure: Change of effect on autonomic dysfunction measured by bladder diary
timeFrame: Change from screening at day 168
measure: Change of effect on quality life of patients with neuro-urological disorders as measured by Qualiveen questionnaire
timeFrame: Change from screening at day 168
measure: Change of effect on autonomic dysfunction as measured by bladder function assessment
timeFrame: Change from screening at day 168
measure: Change of effect on functioning, evaluated by the Spinal Cord Independence Measure (SCIM-III)
timeFrame: Change from baseline at day 168
measure: Change of effect on hand/upper limb function as assessed by the Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP)
timeFrame: Change from baseline at day 168
measure: Change of effect on the Walking Index for Spinal Cord Injury (WISCI
timeFrame: Change from baseline at day 168
measure: Change of effect on 10 meter walk test (10mWT)
timeFrame: Change from baseline at day 168
measure: Change of effect on 6-minute walking test (6MWT)
timeFrame: Change from baseline at day 168
measure: Change of effects on nerve conducting velocity
timeFrame: Change from screening at day 168
measure: Change of effects on somatosensory evoked potentials
timeFrame: Change from screening at day 168
measure: Evaluation of concentration NG-101 in serum (pharmacokinetics)
timeFrame: Change from day 0 at day 84
measure: Evaluation of concentration NG-101 in CSF (pharmacokinetics)
timeFrame: Change from day 0 at day 84
Other outcomes:
Locations:
city: Praha
country: Czechia
facility: Spinal Cord Unit, University Hospital Motol
city: Bayreuth
country: Germany
facility: Klinik für Querschnittgelähmte, Klinikum Bayreuth
city: Berlin
country: Germany
facility: Behandlungszentrum für Rückenmarkverletzte, Unfallkrankenhaus Berlin
city: Bochum
country: Germany
facility: Abteilung für Rückenmarkverletzte, BG Universitätsklinikum Bergmannsheil gGmbH
city: Halle
country: Germany
facility: Zentrum für Rückenmarkverletzte und Klinik für Orthopädie, BG Klinikum Bergmannstrost
city: Heidelberg
country: Germany
facility: Klinik für Paraplegiologie, Universitätsklinikum Heidelberg
city: Hessisch Lichtenau
country: Germany
facility: Zentrum für Tetra- und Paraplegie, Orthopädische Klinik Hessisch Lichtenau gGmbH
city: Murnau Am Staffelsee
country: Germany
facility: Zentrum für Rückenmarksverletzte, Unfallklinik Murnau
city: Tübingen
country: Germany
facility: BG Klinik Tübingen
city: Barcelona
country: Spain
facility: Center for Neurorehabilitation, Fundacio Institut Guttmann
city: Basel
country: Switzerland
facility: Rehab Basel
city: Nottwil
country: Switzerland
facility: Schweizer Paraplegikerzentrum
city: Zürich
country: Switzerland
facility: Universitätsklinik Balgrist
Study officials:
affiliation: Universität Zürich / University Hospital Balgrist
name: Armin Curt, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Heidelberg
name: Norbert Weidner, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.