Back to resultsNISCI - Nogo Inhibition in Spinal Cord Injury (NISCI)
Primary Purpose
Spinal Cord Injury, Acute
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
NG-101
Placebos
Sponsored by
About this trial
This is an interventional treatment trial for Spinal Cord Injury, Acute focused on measuring Tetraplegia, Trauma, Upper limbs function
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
Sites / Locations
- Spinal Cord Unit, University Hospital Motol
- Klinik für Querschnittgelähmte, Klinikum Bayreuth
- Behandlungszentrum für Rückenmarkverletzte, Unfallkrankenhaus Berlin
- Abteilung für Rückenmarkverletzte, BG Universitätsklinikum Bergmannsheil gGmbH
- Zentrum für Rückenmarkverletzte und Klinik für Orthopädie, BG Klinikum Bergmannstrost
- Klinik für Paraplegiologie, Universitätsklinikum Heidelberg
- Zentrum für Tetra- und Paraplegie, Orthopädische Klinik Hessisch Lichtenau gGmbH
- Zentrum für Rückenmarksverletzte, Unfallklinik Murnau
- BG Klinik Tübingen
- Center for Neurorehabilitation, Fundacio Institut Guttmann
- Rehab Basel
- Schweizer Paraplegikerzentrum
- Universitätsklinik Balgrist
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Patients with acute cervical spinal cord injury: NG-101
Patients with acute cervical spinal cord injury: Placebo
Arm Description
Outcomes
Primary Outcome Measures
Change of upper extremity motor scores (UEMS) according to the International Standards for the Neurological Classification of Spinal Cord Injury
Secondary Outcome Measures
Change of effect on motor and sensory function according to the ISNCSCI protocol
Change of effect on autonomic dysfunction measured by bladder diary
Change of effect on quality life of patients with neuro-urological disorders as measured by Qualiveen questionnaire
Change of effect on autonomic dysfunction as measured by bladder function assessment
Change of effect on functioning, evaluated by the Spinal Cord Independence Measure (SCIM-III)
Change of effect on hand/upper limb function as assessed by the Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP)
Change of effect on the Walking Index for Spinal Cord Injury (WISCI
Change of effect on 10 meter walk test (10mWT)
Change of effect on 6-minute walking test (6MWT)
Change of effects on nerve conducting velocity
Change of effects on somatosensory evoked potentials
Evaluation of concentration NG-101 in serum (pharmacokinetics)
Evaluation of concentration NG-101 in CSF (pharmacokinetics)
Full Information
NCT ID
NCT03935321
First Posted
March 25, 2019
Last Updated
April 3, 2023
Sponsor
University of Zurich
Collaborators
EMSCI.org, State Secretariat for Education Research and Innovation, Switzerland, Horizon 2020 - European Commission, Foundation Wings For Life, Swiss Paraplegic Research, Nottwil, Heidelberg University Hospital Spinal Cord Injury Center, KKS Netzwerk
1. Study Identification
Unique Protocol Identification Number
NCT03935321
Brief Title
NISCI - Nogo Inhibition in Spinal Cord Injury
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
May 15, 2019 (Actual)
Primary Completion Date
February 2, 2023 (Actual)
Study Completion Date
February 2, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Zurich
Collaborators
EMSCI.org, State Secretariat for Education Research and Innovation, Switzerland, Horizon 2020 - European Commission, Foundation Wings For Life, Swiss Paraplegic Research, Nottwil, Heidelberg University Hospital Spinal Cord Injury Center, KKS Netzwerk
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injury, Acute
Keywords
Tetraplegia, Trauma, Upper limbs function
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
129 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Patients with acute cervical spinal cord injury: NG-101
Arm Type
Active Comparator
Arm Title
Patients with acute cervical spinal cord injury: Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
NG-101
Intervention Description
6 intrathecal bolus injections, each of 45mg
Intervention Type
Drug
Intervention Name(s)
Placebos
Intervention Description
6 intrathecal bolus injections, each of 45mg
Primary Outcome Measure Information:
Title
Change of upper extremity motor scores (UEMS) according to the International Standards for the Neurological Classification of Spinal Cord Injury
Time Frame
Change from screening at day 168
Secondary Outcome Measure Information:
Title
Change of effect on motor and sensory function according to the ISNCSCI protocol
Time Frame
Change from screening at day 168
Title
Change of effect on autonomic dysfunction measured by bladder diary
Time Frame
Change from screening at day 168
Title
Change of effect on quality life of patients with neuro-urological disorders as measured by Qualiveen questionnaire
Time Frame
Change from screening at day 168
Title
Change of effect on autonomic dysfunction as measured by bladder function assessment
Time Frame
Change from screening at day 168
Title
Change of effect on functioning, evaluated by the Spinal Cord Independence Measure (SCIM-III)
Time Frame
Change from baseline at day 168
Title
Change of effect on hand/upper limb function as assessed by the Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP)
Time Frame
Change from baseline at day 168
Title
Change of effect on the Walking Index for Spinal Cord Injury (WISCI
Time Frame
Change from baseline at day 168
Title
Change of effect on 10 meter walk test (10mWT)
Time Frame
Change from baseline at day 168
Title
Change of effect on 6-minute walking test (6MWT)
Time Frame
Change from baseline at day 168
Title
Change of effects on nerve conducting velocity
Time Frame
Change from screening at day 168
Title
Change of effects on somatosensory evoked potentials
Time Frame
Change from screening at day 168
Title
Evaluation of concentration NG-101 in serum (pharmacokinetics)
Time Frame
Change from day 0 at day 84
Title
Evaluation of concentration NG-101 in CSF (pharmacokinetics)
Time Frame
Change from day 0 at day 84
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Armin Curt, Prof.
Organizational Affiliation
Universität Zürich / University Hospital Balgrist
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Norbert Weidner, Prof.
Organizational Affiliation
University Hospital Heidelberg
Official's Role
Principal Investigator
Facility Information:
Facility Name
Spinal Cord Unit, University Hospital Motol
City
Praha
Country
Czechia
Facility Name
Klinik für Querschnittgelähmte, Klinikum Bayreuth
City
Bayreuth
Country
Germany
Facility Name
Behandlungszentrum für Rückenmarkverletzte, Unfallkrankenhaus Berlin
City
Berlin
Country
Germany
Facility Name
Abteilung für Rückenmarkverletzte, BG Universitätsklinikum Bergmannsheil gGmbH
City
Bochum
Country
Germany
Facility Name
Zentrum für Rückenmarkverletzte und Klinik für Orthopädie, BG Klinikum Bergmannstrost
City
Halle
Country
Germany
Facility Name
Klinik für Paraplegiologie, Universitätsklinikum Heidelberg
City
Heidelberg
Country
Germany
Facility Name
Zentrum für Tetra- und Paraplegie, Orthopädische Klinik Hessisch Lichtenau gGmbH
City
Hessisch Lichtenau
Country
Germany
Facility Name
Zentrum für Rückenmarksverletzte, Unfallklinik Murnau
City
Murnau Am Staffelsee
Country
Germany
Facility Name
BG Klinik Tübingen
City
Tübingen
Country
Germany
Facility Name
Center for Neurorehabilitation, Fundacio Institut Guttmann
City
Barcelona
Country
Spain
Facility Name
Rehab Basel
City
Basel
Country
Switzerland
Facility Name
Schweizer Paraplegikerzentrum
City
Nottwil
Country
Switzerland
Facility Name
Universitätsklinik Balgrist
City
Zürich
ZIP/Postal Code
8008
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
29869587
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.
Results Reference
background
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NISCI - Nogo Inhibition in Spinal Cord Injury
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