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Trial record 2 of 32 for:    nkg2d

A Phase I/II Study of Universal Off-the-shelf NKG2D-ACE2 CAR-NK Cells for Therapy of COVID-19

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04324996
Recruitment Status : Recruiting
First Posted : March 27, 2020
Last Update Posted : March 27, 2020
Sponsor:
Collaborator:
Chongqing Sidemu Biotechnology Technology Co.,Ltd.
Information provided by (Responsible Party):
Chongqing Public Health Medical Center

Brief Summary:

SARS-CoV-2 infection mainly leads to interstitial pneumonia. The patients with low immunity have more serious conditions. At present, there is no specific drug/therapy available for COVID-19. NK cells are the major cells of the natural immune system, which are essential for innate immunity and adaptive immunity, and are indispensable in the defense of virus infection. NKG2D is an activating receptor of NK cells, which can recognize and thus clear virus infected cells. NK cells modified by CAR play a role in targeted cell therapy, and have benn demonstrated very safe without severe side effects such as cytokine releasing syndromes. The survival time of NK cells will be very short if there is no IL-15-sustained support after adoptive transfer into the body. In comparison with natural IL-15 in vivo, IL-15 superagonist (sIL-15/IL-15Rɑ chimeric protein) has increased the activity by nearly 20 times and as well as improved pharmacokinetic characteristics with longer persistence and enhanced target cytotoxicity. CAR-T cell-mediated cytokine release syndrome (CRS) and neurotoxicity have been shown to be abrogated through GM-CSF neutralization. ACE2 is the receptor of SARS-CoV-2 and binds to S protein of the virus envelope. We have constructed and prepared the universal off-the-shelf IL15 superagonist- and GM-CSF neutralizing scFv-secreting NKG2D-ACE2 CAR-NK derived from cord blood. By targeting the S protein of SARS-CoV-2 and NKG2DL on the surface of infected cells with ACE2 and NKG2D, respectively, and with the strong synergistic effect of IL15 superagonist and CRS prevention through GM-CSF neutralizing scFv, we hope that the SARS-CoV-2 virus particles and their infected cells can be safely and effectively removed, thus providing a safe and effective cell therapy for COVID-19. In addition, ACE2 CAR-NK cells can competitively inhibit SARS-CoV-2 infection of type II alveolar epithelial cells and other important organ or tissue cells through ACE2 so as to make SARS-CoV-2 abortive infection (i.e., no production of infectious virus particles).

This project is an open, randomized, parallel, multicenter phase I/II clinical trial. The NKG2D-ACE2 CAR-NK cells secreting super IL15 superagonist and GM-CSF neutralizing scFv are going to be give by intravenous infusion (108 cells per kilogram of body weight, once a week) for the treatment of 30 patients with each common, severe and critical type COVID-19, respectively.


Condition or disease Intervention/treatment Phase
COVID-19 Biological: NK cells,IL15-NK cells,NKG2D CAR-NK cells,ACE2 CAR-NK cells,NKG2D-ACE2 CAR-NK cells Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Universal Off-the-shelf NKG2D-ACE2 CAR-NK Cells Secreting IL15 Superagonist and GM-CSF-neutralizing scFv for Therapy of COVID-19
Actual Study Start Date : March 21, 2020
Estimated Primary Completion Date : May 31, 2020
Estimated Study Completion Date : September 30, 2020

Arm Intervention/treatment
Experimental: NK cells
The NK cells are going to be give by intravenous infusion (10E8 cells per kilogram of body weight, once a week) .
Biological: NK cells,IL15-NK cells,NKG2D CAR-NK cells,ACE2 CAR-NK cells,NKG2D-ACE2 CAR-NK cells
The CAR-NK cells are universal off the shelf NK cells enriched from umbilical cord blood and engineered genetically.

Experimental: IL15-NK cells
The NK cells secreting super IL15 superagonist are going to be give by intravenous infusion (10E8 cells per kilogram of body weight, once a week) .
Biological: NK cells,IL15-NK cells,NKG2D CAR-NK cells,ACE2 CAR-NK cells,NKG2D-ACE2 CAR-NK cells
The CAR-NK cells are universal off the shelf NK cells enriched from umbilical cord blood and engineered genetically.

Experimental: NKG2D CAR-NK cells
The NKG2D CAR-NK cells are going to be give by intravenous infusion (10E8 cells per kilogram of body weight, once a week).
Biological: NK cells,IL15-NK cells,NKG2D CAR-NK cells,ACE2 CAR-NK cells,NKG2D-ACE2 CAR-NK cells
The CAR-NK cells are universal off the shelf NK cells enriched from umbilical cord blood and engineered genetically.

Experimental: ACE2 CAR-NK cells
The ACE2 CAR-NK cells are going to be give by intravenous infusion (10E8 cells per kilogram of body weight, once a week).
Biological: NK cells,IL15-NK cells,NKG2D CAR-NK cells,ACE2 CAR-NK cells,NKG2D-ACE2 CAR-NK cells
The CAR-NK cells are universal off the shelf NK cells enriched from umbilical cord blood and engineered genetically.

Experimental: NKG2D-ACE2 CAR-NK cells
The NKG2D-ACE2 CAR-NK cells secreting IL15 superagonist and GM-CSF-neutralizing scFv are going to be give by intravenous infusion (10E8 cells per kilogram of body weight, once a week).
Biological: NK cells,IL15-NK cells,NKG2D CAR-NK cells,ACE2 CAR-NK cells,NKG2D-ACE2 CAR-NK cells
The CAR-NK cells are universal off the shelf NK cells enriched from umbilical cord blood and engineered genetically.




Primary Outcome Measures :
  1. Clinical response [ Time Frame: Up to 28 days ]
    the efficacy of NKG2D-ACE2 CAR-NK cells in treating severe and critical 2019 new coronavirus (COVID-19) pneumonia

  2. Side effects in the treatment group [ Time Frame: Up to 28 days ]
    the safety and tolerability of NKG2D-ACE2 CAR-NK cells in patients with severe and critical 2019 new coronavirus (COVID-19) pneumonia



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Sign written informed consent;
  2. Age ≥18 years;
  3. Conforms to the NCP Critical and Critical Diagnostic Standards, namely "Pneumonitis Diagnosis and Treatment Scheme for New Coronavirus Infection (Trial Version 6)". Comprehensive judgment based on epidemiological history, clinical manifestations and etiological examination;
  4. The course of disease is within 14 days after the onset of illness;
  5. Willing to collect nasopharyngeal or oropharyngeal swabs before administration.

Exclusion Criteria:

  1. Patients participating in clinical trials of other drugs;
  2. pregnant or lactating women;
  3. ALT / AST> 5 times ULN, or neutrophils <0.5 * 109 / L, or platelets less than 50 * 109 / L;
  4. Expected survival time is less than 1 week;
  5. A clear diagnosis of rheumatism-related diseases;
  6. Long-term oral anti-rejection drugs or immunomodulatory drugs;
  7. Patients hypersensitive to NK cells and their preservation solution.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04324996


Contacts
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Contact: Min Liu, A.B 13668072999 gwzxliumin@foxmail.com
Contact: Jimin Gao, PhD 0577-86699341 jimingao64@163.com

Locations
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China
Chongqing Public Health Medical Center Recruiting
Chongqing, China
Contact: Min Liu, A.B    13668072999    gwzxliumin@foxmail.com   
Sponsors and Collaborators
Chongqing Public Health Medical Center
Chongqing Sidemu Biotechnology Technology Co.,Ltd.
Investigators
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Principal Investigator: Min Liu, A.B Chongqing Public Health Center
Publications:

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Responsible Party: Chongqing Public Health Medical Center
ClinicalTrials.gov Identifier: NCT04324996    
Other Study ID Numbers: ChongqingPublicHMC
First Posted: March 27, 2020    Key Record Dates
Last Update Posted: March 27, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Chongqing Public Health Medical Center:
NKG2D-ACE2 CAR-NK
IL15 superagonist
GM-CSF-neutralizing scFv
COVID-19