Neuromyelitis Optica
Conditions
Brief summary
This is a single-arm, open-label, single-center, phase I study. The primary objective is to evaluate the safety of CD19 CAR-T therapy for patients with relapsed or refractory Neuromyelitis Optica, and to evaluate the pharmacokinetics of CD19 CAR-T in patients.
Interventions
DRUGCAR-T cells injection
CAR-T cells in the treatment of R/R neuromyelitis optica
Sponsors
Yake Biotechnology Ltd.
Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Age 18-60 and gender unlimited; * 2\. NMOSD diagnosed based on the 2015 NMOSD International Consensus Diagnostic Criteria; * 3\. Diagnostic criteria for AQP4-IgG positive NMOSD Diagnostic criteria for AQP4-IgG positive NMOSD 1. At least 1 core clinical feature 2. Using reliable methods to detect positive AQP4-IgG (CBA method) 3. Exclude other diagnoses. Core clinical features <!-- --> 1. ＯＮ 2. Acute myelitis 3. Posterior region syndrome, unexplained paroxysmal hiccup, nausea, and vomiting 4. Other brainstem syndromes 5. Symptomatic episodic sleeping sickness, diencephalic syndrome, brain MRI with NMOSD characteristic diencephalic lesions 6. Cerebral syndrome with NMOSD characteristic brain lesions * 4\. Corticosteroids combined with immunosuppressants (azathioprine or mycophenolate mofetil or rituximab) still relapse after treatment； * 5\. At least 2 relapses within the past 12 months or at least 3 relapses within the past 24 months, and at least 1 recurrence within the 12 months prior to screening； * 6\. The estimated survival time is more than 12 weeks; * 7\. Women of childbearing age who have negative urine pregnancy test before medication administration and agree to take effective contraceptive measures during the trial period until the last follow-up
Exclusion criteria
* 1\. Epilepsy history or other central nervous system disease; * 2\. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythm ia in the past; * 3\. Pregnant (or lactating) women; * 4\. Patients with severe active infections; * 5\. Active infection of hepatitis B virus or hepatitis C virus; * 6\. Systemic steroids have used in the 4 weeks before participating in the treatment (except recently or currently using inhaled steroids); * 7\. Those who have used any gene therapy products before; * 8\. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal; * 9\. Serum creatinine \> 2.5mg/dl or ALT / AST \> 3 times ULN or bilirubin \> 2.0mg/dl; * 10\. Those who suffer from other uncontrolled diseases are not suitable to join the study; * 11\. HIV infection; * 12\. Any situation that the researchers believe may increase the risk of patients or interfere with the test results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limited toxicity (DLT) | From date of initial treatment to Day 28 post CAR-T infusion. | Dose limited toxicity |
| AE and SAE | From admission to the end of the follow-up, up to 2 years | Adverse event and serious adverse event |
| Maximum tolerable dose | From date of initial treatment to Day 28 post CAR-T infusion. | Maximum tolerable dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MRI active lesions | days 90 | Proportion of subjects with ≥1 active lesions at Day 90 |
| Changes in optimal corrected vision | days 28 and 90 | Changes in optimal corrected vision (Log MAR) |
| Changes in serum AQP4-IgG titer after infusion | days 7, 14, 21, 28 and 90 | Changes in serum AQP4-IgG titer after infusion |
| Changes in the plexiform layer of macular ganglion cells (mGCIPL) | 2 years | Proportion of subjects with significant mGCIPL thickness changes |
| Changes of nerve fiber layer around the retinal papilla(pRNFL) | 2 years | Change in RNFL by optical coherence tomography over trial |
| Annual recurrence rate (ARR) of NMOSD | From admission to the end of the follow-up, up to 2 years | Annual recurrence rate (ARR) of NMOSD |
| Changes in the expanded disability status scale (EDSS) score from baseline | days 7, 14, 21, 28 ,56 and 90 | EDSS:0 (normal neurological exam) to 10 (death due to MS),Higher scores indicate greater disability (worse outcome)，Score reduction suggests functional improvement |
Countries
China
Outcome results
None listed