Clinical trial NCT05828212: Evaluate the Safety and Efficacy of CAR-T Cells in the Treatment of R/R Neuromyelitis Optica
Official title: A Study on the Safety and Efficacy of Chimeric Antigen Receptor T Cells in the Treatment of Recurrent/Refractory Neuromyelitis Optica
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Neuromyelitis Optica
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2023-04-25
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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  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.

Primary outcomes:
measure: Dose limited toxicity (DLT)
timeFrame: From date of initial treatment to Day 28 post CD19 CAR-T infusion.
measure: AE and SAE
timeFrame: From admission to the end of the follow-up, up to 2 years
measure: Maximum tolerable dose
timeFrame: From date of initial treatment to Day 28 post CD19 CAR-T infusion.
Secondary outcomes:
measure: Changes in serum AQP4-IgG titer after infusion
timeFrame: days 7, 14, 21, 28 and 90
measure: Annual recurrence rate (ARR) of NMOSD
timeFrame: From admission to the end of the follow-up, up to 2 years
measure: Changes in the expanded disability status scale (EDSS) score from baseline
timeFrame: days 7, 14, 21, 28 ,56 and 90
measure: MRI active lesions
timeFrame: days 90
measure: Changes in optimal corrected vision
timeFrame: days 28 and 90
measure: Changes of nerve fiber layer around the retinal papilla(pRNFL)
timeFrame: 2 years
measure: Changes in the plexiform layer of macular ganglion cells (mGCIPL)
timeFrame: 2 years
measure: Changes in Flash Visual Evoked Potential (FVEP)
timeFrame: 2 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The first affiliated hospital of medical college of zhejiang university
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: He Huang, MD
role: PRINCIPAL_INVESTIGATOR
References: