An Open-labeled Phase II Study to Evaluate the Efficacy and Safety of GXNPC-1 in Patients with Chronic Stroke

GXNPC1 Injections for Chronic Stroke

The primary objective of this study is to evaluate the efficacy for subjects with chronic stroke after GXNPC-1 injection.

This is an open-label, single center, sequentially study in subjects with chronic stroke. Considering 20% dropout rate (based on evaluable versus treated patients), approximately 15 subjects will be enrolled, and at least 12 subjects will be evaluable. Cohort 1 will recruit the first 3 evaluable subjects assigned to receive low dose of GXNPC-1. The following 3 evaluable subjects will be enrolled sequentially and treated with high dose of GXNPC-1 in cohort 2. In cohort 3, another 6 evaluable subjects will be enrolled to take high dose of GXNPC-1. There will be 2 parts of this study including GXNPC-1 preparation and GXNPC-1 treatment in chronic stroke subjects, respectively.

Inclusion Criteria:

1. Male or female who are aged between 45 and 85 years old on date of consent
2. Post-stroke between 6 months and 15 years at the screening
3. Subjects who have had stroke(s) in carotid artery distribution area, and the location of stroke should be diagnosed by magnetic resonance image (MRI)
4. Subjects who have had the brain injured area with diameter between 0.5 and 10 cm according to MRI evaluation
5. Subjects who have National Institutes of Health Stroke Scale (NIHSS) score between 8 and 30 at the screening
6. Subjects who had stroke with hemiparesis (remaining residual limb movement, defined as score less than 4 on questions 5 or 6 on the NIHSS for the affected limbs) at screening.
7. Subjects who have stable NIHSS (±3) for at least 2 weeks from Visit 1 (screening) to Visit2 (prior to operation)
8. Subjects with systolic blood pressure less than 200 mmHg (an average based on ≥2 readings) at screening, prior to the operation for fat tissue acquisition (Visit 2), and before the surgery for ADSC administration (Visit 3)
9. Subjects with International normalized ration (INR) < 2.5, and platelet between 1 × 105/μL and 5 × 105/μL at the screening
10. Female subjects with childbearing potential should be confirmed of not being pregnant or lactating at the screening and during the study.
11. All male subjects and female subjects with child-bearing potential (between puberty and 2 years after menopause) should use reliable contraception method(s), such as tubal ligation, vasectomy, intrauterine device (IUD), intrauterine system (IUS), hormonal contraception or condom, during this study when they have sexual behavior.
12. Neurology physician judges the recent symptoms in subjects are correlated to the stroke area.
13. Subjects or the legally acceptable representative are willing to sign informed consent form (ICF).

Exclusion Criteria:

1. Subjects who are suffered by clinically significantly autoimmune conditions, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS) or psoriasis

2. Subjects who are unable to undergo MRI and Computed tomography (CT) scans for any reason

3. Subjects who have significant multiple stenosis (>50% stenosis) in intracranial blood vessels

4. Subjects whose cause of stroke belongs to uncommon causes (refer to Vasc Health Risk Manag. 2015:11 157-164), including but not limited to:

   1. Non-atherosclerotic angiopathies: cervicocephalic atrial dissection, cerebral amyloid angiopathy, fibromuscular dysplasia, and migraine-induced stroke, etc.;
   2. Hematologic conditions: hypercoagulable state due to deficiencies of protein C, protein S, or antithrombin, factor V Leiden mutation, prothrombin gene G20210Amutation, acquired hypercoagulable state, antiphospholipid syndrome, hyperhomocysteinemia, sickle cell disease, etc.;
   3. Genetic: Fabry disease, CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes), Marfan syndrome, Neurofibromatosis, and Sturge-Weber Syndrome, etc.;
   4. Inflammatory and infectious: vasculitis (primary angilitis of the CNS, Sjögren syndrome, Wegener's granulomatosis), temporal arteritis, Takayasu disease, Behçet's syndrome, Neurosarcoidosis, Neurocysticercosis, varicella zoster virus, neurosyphilis, and tuberculous meningitis, etc.

5. Subjects receiving antiplatelets (e.g., aspirin and persantin) and/or anticoagulants (e.g., warfarin) cannot temporarily cease the treatment within 3 days before ADSCs administration (Visit 3).

6. Subjects who receive systemic immunosuppressive treatments, immunotherapy, or cytotoxic drug within 1 month before screening

7. Subjects with inadequate hepatic function at the screening visit: Alanine aminotransaminase (ALT), Aspartate aminotransaminase (AST), and alkaline phosphatase (ALP) ≥ 2X upper limit of normal (ULN).

8. Subjects with inadequate renal function at the screening visit: Blood urea nitrogen (BUN) ≥ 30 mg/dl; serum creatinine ≥ 3 mg/dl

9. Subjects who have medical historical or clinically active spinal injury, Alzheimer's disease, Parkinson's disease, spinocerebellar ataxia (SCA), spinal muscular atrophy (SMA) or other clinically significant neurological diseases that will confound the evaluation of this study

10. Subjects who have clinically severe and/or life-threatening disease(s) such as uncontrolled diabetes or malignant tumor

11. Subjects who have risk for the following infectious diseases: human immunodeficiency virus (HIV), syphilis, or human transmissible spongiform encephalopathy (TSE), such as Creutzfeldt-Jakob disease (CJD)

12. Subject who fails to generate adequate amount of ADSCs before administration at Visit 3

13. Female subject who is lactating, pregnant, or planned to be pregnant

14. Subject with known or suspected hypersensitivity to GXNPC-1 or its excipients

15. Subject with any complication by chest X-ray and electrocardiogram (ECG) evaluation

16. Subjects who have participated in other investigational studies and received any treatment within 4 weeks prior to screening

17. Subjects not suitable to participate the trial as judged by the investigator(s)