NeuroRise: Intrathecal CE-1 Treatment for Traumatic SCI

Inclusion criteria

• Once the voluntary nature of the study is explained in detail, the participant must be willing to provide written informed consent and complete HIPAA documentation before conducting any study-related procedure. A signed written informed consent and ability to comply with the study protocol according to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and local regulations is required.
• Male or female aged 18 years and older at the time of enrollment
• Females of childbearing potential must have a negative pregnancy test prior to receiving the study drug and will agree to use adequate contraception (hormonal/barrier method or abstinence) from the time of screening to a period of 1 year following completion of the drug treatment cycle. Females of childbearing potential are defined as premenopausal and not surgically sterilized, or post-menopausal for fewer than two years. If the urine pregnancy test is positive, the study drug will not be administered, and the result will be confirmed by a serum β-hCG test. β-hCG tests will be performed at a central clinical laboratory, whereas urine pregnancy tests will be performed by qualified personnel using a kit.
• Females becoming pregnant during the study will continue to be monitored for the duration of the study or completion of the pregnancy, whichever is longer. Monitoring will include perinatal and neonatal outcomes. Any serious adverse events (SAE) associated with pregnancy will be recorded.
• SCI categorized as either complete (AIS grade A) or incomplete (AIS grade B, C or D) at the time of recruitment.
• Injuries located below the C2 level confirmed by MR imaging.
• SCI must be traumatic, blunt/non-penetrating in nature, and not degenerative.
• Full understanding of the requirements of the study and willingness to comply with the treatment plan, laboratory tests, diagnostic imaging, complete physical and neurologic examination, and follow-up visits and assessments.
• Full understanding of the requirements of their rehabilitation program prescribed by physical and occupational therapists.
• Injury within 10 years before enrollment or screening period. Both acute and chronic SCI patients may be enrolled. Chronic SCI is defined as at least one year post-injury with stabilized neurological function.
• The participant must be able to tolerate intrathecal injections.
• The participant must have negative serology for HIV, VDRL, Hepatitis B and C
• Adequate vital organ function defined by normal laboratory values for creatinine, ALT, AST, total bilirubin, NT-ProBNP. If these labs are out of range, they must be reviewed by PI and confirmed. Rescreening can be done after treatment and retesting.
• Blood platelets count equal to or higher than 100,000 /μL and INR level equal to or less than 1.5 must be encountered.

Exclusion criteria

• Pregnant or nursing, or planning on becoming pregnant during the study period
• SCI initially classified as AIS grade E at the time of injury
• SCI located above C2 level confirmed by magnetic resonance imaging (MRI).
• History of receiving MSC, gene or exosome therapy for any indications
• History of intra-spinal infection
• History of superficial infection in the index spinal level within 6 months of enrollment
• Evidence of current superficial infection affecting the index spinal level at the time of enrollment
• On chronic, immunosuppressive transplant therapy or having a chronic, immunosuppressive state, including chronic use of systemic steroids/corticosteroids. Use of steroids/corticosteroids in the acute SCI phase is permissible but the participant must have been off steroids for at least 14 days prior to the first injection and cannot take steroids for at least one month after injection.
• Taking anti-rheumatic disease medication (including methotrexate or other antimetabolites) within 3 months prior to study enrollment.
• Ongoing infectious disease, including but not limited to tuberculosis, HIV, hepatitis, and syphilis.
• Fever, defined as temperature above 99ºF/37.2ºC or mental confusion at the time of IPA.
• Clinically significant cardiovascular (e.g., history of myocardial infarction, congestive heart failure or uncontrolled hypertension > 90 mmHg diastolic and/or 180 mmHg systolic), neurological (e.g., stroke, TIA) renal, hepatic or endocrine disease (e.g., diabetes, osteoporosis).
• History of malignancy including melanoma except for localized skin cancers (with no evidence of metastasis, significant invasion, or re-occurrence within three years of baseline). Any other malignancy will not be allowed. Provided they have not demonstrated clinical signs or symptoms of infection and have not required treatment, participants with large granular lymphocytic leukemia, upon consultation with their Hematologist/Oncologist, may be considered but should undergo additional testing at screening.
• History of blood dyscrasia, including but not limited to anemia, thrombocytopenia, and monoclonal gammopathy.
• History of bleeding disorders and actual levels of blood platelet lower than 100,000/μL and/or INR equal to or higher than 1.5.
• History or presence of brain injury, hydrocephalus, meningitis, cerebral palsy, altered consciousness, signs/symptoms of neurodegenerative disorders (e.g., stroke, amyotrophic lateral sclerosis, multiple sclerosis, etc.), based on medical history and at the discretion of the investigator.
• Participation in a study of an experimental drug or medical device within 3 months of study enrollment
• Known allergy to local anesthetics of other components of the study drug.
• Any contraindication to MRI scan according to MRI guidelines, or unwillingness to undergo MRI procedures.
• History of or current evidence of alcohol or drug abuse or dependence, recreational use of an illicit drug or prescription medications, or use of medical marijuana within 28 days of study entry
• Diagnosis of schizophrenia or bipolar disorder
• Participants with untreated baseline depression, diagnosed by the Beck Depression Inventory, past medical history, and baseline assessment conducted by a psychologist or a psychiatrist. Participants with depression or anxiety disorders who are in remission or receiving treatment can be enrolled in the study.
• Any severe condition pre-existing before or after traumatic SCI at the discretion of the Principal Investigator (PI).