spinal cord injury MedDRA version: 20.1 Level: PT Classification code 10041554 Term: Spinal cord injury cervical System Organ Class: 10022117 - Injury, poisoning and procedural complications MedDRA version: 20.1 Level: PT Classification code 10041552 Term: Spinal cord injury System Organ Class: 10022117 - Injury, poisoning and procedural complications
Conditions
Interventions
Product Name: NG-101 / ATI355
Pharmaceutical Form: Concentrate for solution for injection
INN or Proposed INN: NA
Current Sponsor code: NG-101 or ATI355
Other descriptive name: human monoclonal antibo
Sponsors
University Zurich, University Hospital Balgrist, Spinal Cord Injury Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, 18 through 70 years of age 2. Acute cervical spinal cord injury (SCI) (Neurological level of injury C1 = lesion = 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) 3. 4-28 days post-injury (i.e. initiation of bolus injection within 4-28 days post-injury) 4. Tetraplegic patients who are allowed to start treatment are those who either do not require mechanical ventilation or who do not completely depend on mechanical ventilation but show some degree of spontaneous ventilation. Only those modes of ventilation where the patient show active initiation of breathing are allowed (e.g. continuous positive airway pressure (CPAP)) 5. Hemodynamically and clinically stable according to the acute SCI condition at baseline 6. For patients of childbearing potential , use of reliable means of contraception 7. Written informed consent by patient before any study assessment is performed. If the patient is only able to consent orally a witness signs and confirms the patient’s consent, 8. Cooperation and willingness to complete all aspects of the study 9. Ability of subject to understand character and individual consequences of the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 132 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 1. Complete anatomical transection confirmed by magnetic resonance imaging (MRI). 2. Trauma caused by ballistic or other injury that directly penetrates the spinal cord including gunshot and knife wounds. 3. Multiple levels of clinically relevant spinal cord lesions. 4. Major brachial or lumbar plexus damage/trauma. 5. Significant head trauma (e.g. cortical damage/lesion), or other injury that was, in the opinion of the investigator, sufficient to interfere with the assessment of the spinal cord function or otherwise compromise the validity of the patient's data. 6. Other significant pre-existing or current severe systemic disease such as lung, liver (exception: history of uncomplicated Hepatitis A), gastrointestinal, cardiac, immunodeficiency (including anamnestic known HIV) or kidney disease; or active malignancy or any other condition as determined by history or laboratory investigation that could cause a neurological deficit including syphilis, myelopathy, clinically relevant polyneuropathy, etc. 7. History of or an acute episode of Guillain-Barre syndrome. 8. History of recent (6 months) meningitis or meningoencephalitis. 9. History of refractory epilepsy. 10. Patients with uncontrolled bleeding diathesis and/or who require uninterrupted concomitant therapeutic anticoagulation (e.g. phenoprocoumon (Marcumar®), heparin/heparinoids and new oral anticoagulants) at a higher dose than for the prophylaxis of venous thromboembolism 11. Presence of any unstable medical or psychiatric condition (defined by the Diagnostic and Statistical Manual of Mental Disorders, Edition 4 (DSM-IV)) that could reasonably have been expected tosubject the patient to unwarranted risk from participation in the study or result in a significant deterioration of the patient's clinical course. 12. Drug dependence (as defined by DSM-IV) any time during the 6 month’s preceding study entry. 13. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL). 14. History of a life-threatening allergic or immune mediated reaction. 15. Patients with the presence of infection around the location where the spinal needle insertions are planned for applying the intrathecal injections. 16. Inability to communicate effectively with the neurological examiner such that the validity of the patient's data could be compromised. 17. Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations. 18. Patients who are unconscious, including those patients who are unconscious due to medication causing marked sedation. 19. History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate efficacy of acute treatment (initiation of drug treatment within 4 - 28 days post-injury) with NG-101 by repeated intrathecal (i.t.) bolus injections on day 168.;Secondary Objective: To evaluate the safety of acute treatment (initiation of drug treatment within 4 - 28 days post--injury) with NG-101 by repeated intrathecal bolus injections (6 injections of 45 mg each over 4 weeks) ?- Adverse Events (Frequency, type, duration and intensity of AEs and SAEs) ?- Relationship of AE/SAE frequency and time and duration of study medication administration ?- Documented reasons for any unplanned study medication interruptions and/or withdrawal from the study ?- Vital signs (blood pressure, heart frequency, body temperature) ? -Muscle spasticity measured by the Modified Ashworth Scale ? - Effect on pain (neuropathic pain and non-neuropathic pain) assessed by SCI pain data set, allodynia questionnaire and SCIPI;Primary end point(s): Upper extremity motor scores (UEMS) according to the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI);Timepoint(s) of evaluation of this end point: The primary efficacy endpoint (UEMS recovery) will be analysed by the comparison of the mean of the control and treatment groups. Also the secondary efficacy endpoints will be analysed by comparing the means of outcomes between the control and treatment groups. The primary criterion is the UEMS recovery score at day 168. No interim analysis is planned. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Effect on motor and sensory function according to the ISNCSCI protocol (ASIA impairment scale, ASIA lower extremities motor score (LEMS) and sensory scores (light touch (LT), pin prick (PP)). ? Effect on autonomic dysfunction (i.e. bladder function as measured by bladder diary, Qualiveen questionnaire, bladder function questionnaire) ? Effect on functioning evaluated by the Spinal Cord Independence Measure (SCIM-III). ? Effect on hand/upper limb function as assessed by the Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) subscales. ? Effect on the Walking Index for Spinal Cord Injury (WISCI), 10 meter walk test (10mWT) and the 6- minute walking test (6MWT). ? Effect on neurophysiological parameters (nerve conducting velocity, Somatosensory evoked potentials) ? To evaluate the pharmacokinetics (PK) and immunogenicity of NG-101.;Timepoint(s) of evaluation of this end point: For the exact time points of evaluation refer to assessment schedule. | — |
Countries
Czech Republic, Germany, Italy, Spain, Switzerland
Contacts
Public ContactSpinal Cord Injury Center
Heidelberg University Hospital
Outcome results
None listed