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Trial record 1 of 1 for:    NCT04365101
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Natural Killer Cell (CYNK-001) Infusions in Adults With COVID-19 (CYNK-001-COVID-19) (CYNK001COVID)

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ClinicalTrials.gov Identifier: NCT04365101
Recruitment Status : Recruiting
First Posted : April 28, 2020
Last Update Posted : October 19, 2020
Sponsor:
Collaborators:
IDRI
Lung Biotechnology PBC
California Institute for Regenerative Medicine (CIRM)
Information provided by (Responsible Party):
Celularity Incorporated

Brief Summary:
This study is a Phase 1 / 2 trial to determine the safety and efficacy of CYNK-001, an immunotherapy containing Natural Killer (NK) cells derived from human placental CD34+ cells and culture-expanded, in patients with moderate COVID-19 disease.

Condition or disease Intervention/treatment Phase
Coronavirus Coronavirus Infection Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia Pneumonia, Viral Lung Diseases Respiratory Tract Disease Respiratory Tract Infections Coronaviridae Infections Nidovirales Infections RNA Virus Infections Virus Disease Immunologic Disease ARDS Immunologic Factors Physiological Effects of Drugs Antiviral Agents Anti-infective Agents Analgesics Antimetabolites, Antineoplastic Biological: CYNK-001 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 86 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Phase I will evaluate the safety and efficacy of multiple doses of CYNK-001 (Days 1,4, and 7) in 14 patients.

Phase II will utilize a randomized, open-label design; multiple doses of CYNK-001 will be compared to the control group: Best Supportive Care. Up to 72 patients will be included in the Phase II portion of the study with a 1:1 randomization ratio.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Human Placental Hematopoietic Stem Cell Derived Natural Killer Cells (CYNK-001) for the Treatment of Adults With COVID-19
Actual Study Start Date : May 13, 2020
Estimated Primary Completion Date : December 30, 2020
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase I
CYNK-001 infusions on Days 1, 4, and 7
Biological: CYNK-001
CYNK-001 is an allogeneic off the shelf cell therapy enriched for CD56+/CD3- NK cells expanded from human placental CD34+ cells.

Active Comparator: Phase II
Randomized, open label; CYNK-001 infusions on Days 1, 4, and 7 compared to Control Group: Best Supportive Care
Biological: CYNK-001
CYNK-001 is an allogeneic off the shelf cell therapy enriched for CD56+/CD3- NK cells expanded from human placental CD34+ cells.




Primary Outcome Measures :
  1. Phase 1: Frequency and Severity of Adverse Events (AE) [ Time Frame: Up to 6 months ]
    Number and severity of adverse events

  2. Phase 1: Rate of clearance of SARS-CoV-2 [ Time Frame: Up to 6 months ]
    Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR

  3. Phase 1: Rate of clinical improvement [ Time Frame: Up to 6 months ]
    Proportion of subjects who improved clinical symptoms related to lower respiratory tract infection, as measured by National Early Warning Score 2 (NEWS2) score.

  4. Phase 2: Time to Clearance of SARS-CoV-2 [ Time Frame: Up to 28 days ]
    Time from the date of randomization to the clearance of SARS-CoV-2 by rRT-PCR. Negative results will need to be confirmed by a second negative result in the same sample type at least 24 hours after the first negative result.

  5. Phase 2: Time to Clinical Improvement by NEWS2 Score [ Time Frame: Up to 28 days ]
    Time from the date of randomization to the first date of improved clinical symptoms related to lower respiratory tract infection. Improvement as measured by National Early Warning Score 2 (NEWS2) Score.


Secondary Outcome Measures :
  1. Rate of Clearance of SARS-CoV-2 [ Time Frame: Up to 6 months ]
    Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR

  2. Phase 2: Frequency and Severity of Adverse Events (AE) [ Time Frame: up to 6 months ]
    Number and severity of adverse events

  3. Overall Clinical Benefit by time to medical discharge [ Time Frame: up to 6 months ]
    Time to medical discharge as an assessment of overall clinical benefit

  4. Overall Clinical Benefit by hospital utilization [ Time Frame: up to 6 months ]
    Hospital utilization will be measured as an assessment of overall clinical benefit

  5. Overall Clinical Benefit by measuring mortality rate [ Time Frame: up to 6 months ]
    Mortality rate will be measured as an assessment of overall clinical benefit

  6. Impact of CYNK-001 on sequential organ failure assessment (SOFA) score [ Time Frame: Up to 28 days ]
    Assess the impact of CYNK-001 on changes in sequential organ failure assessment (SOFA) score.

  7. Time to Pulmonary Clearance [ Time Frame: Up to 28 days ]
    Time from randomization to the date of disappearance of virus from lower respiratory tract infection (LRTI) specimen where it has previously been found (induced sputum, endotracheal aspirate).

  8. Supplemental oxygen-free days [ Time Frame: Up to 28 days ]
    For ventilatory support subjects, the days with supplemental oxygen-free.

  9. Proportion of subjects requiring ventilation [ Time Frame: Up to 28 days ]
    Proportion of subjects who need invasive or non-invasive ventilation



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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

Patient Inclusion Criteria:

  • Patient has confirmed positivity for SARS-CoV-2 as measured by rRT-PCR or other approved test to detect SAR-CoV-2 per institutional practice.
  • Patient is experiencing at least 2 of the 3 signs/symptoms of the list below:

    1. Fever ≥ 38 C°
    2. Cough
    3. Positive disease-related chest x-ray
  • Patient is ≥ 18 years of age at the time of signing the Study informed consent form (ICF).
  • Patient understands and voluntarily signs the Study ICF prior to any study-related assessments/procedures are conducted.
  • Patient is willing and able to adhere to the study schedule and other protocol requirements.
  • SpO2 ≥ 88% with the following specifications:

Phase I: SpO2 ≥ 88%

  • Supplemental oxygen is permitted as delivered by nasal cannula and/or face mask.
  • Patients who require supplemental oxygen must be between the age of 18 and 72 years.

Phase II: SpO2 ≥ 88%

  • Patients must be greater than 18 years of age.
  • Ability to be off immunosuppressive drugs for 3 days prior to infusion, unless clinically indicated. Steroids are permitted if clinically indicated and at the discretion of the treating physician.
  • Female of childbearing potential (FCBP)* must not be pregnant and agree to not becoming pregnant for at least 28 days following the last infusion of CYNK-001. FCBP must agree to use an adequate method of contraception during the treatment period.

    • FCBP is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
  • Male Patients must agree to use a condom during sexual contact for at least 28 days following the last infusion of CYNK-001, even if he has undergone a successful vasectomy.

Patient Exclusion Criteria

  • Patient requires supplemental oxygen delivered by mechanical ventilation, either invasive or bilevel positive airway pressure.
  • Patient admitted to Intensive Care Unit / Pulmonary Acute Care Unit designated area with severe pulmonary pneumonia, ARDS or Sepsis.
  • Patient is pregnant or breastfeeding.
  • Patient has a history of severe asthma and is presently on chronic medications or has a history of other symptomatic pulmonary disease.
  • Patient has any other organ dysfunction [Common Terminology Criteria for AEs (CTCAE) Version 5.0 Grade 3] that will interfere with the administration of the therapy according to this protocol.
  • Patient has inadequate organ function as defined below at time of Treatment Eligibility Period:

    1. Patient has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase ≥ 5 x the upper limit of normal (ULN). (It is anticipated that the infection may impact liver.)
    2. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2 as calculated using the Modification of Diet in Renal Disease Study equation (Levey, 2006) or history of an abnormal eGFR < 60. A decline of > 15 mL/min/1.73 m^2 below normal in the past year prior to infection. (It is anticipated that the infection may impact renal function.)
    3. Patient has a bilirubin level > 2 mg/dL (unless Patient has known Gilbert's Syndrome).
  • Patient has a known sensitivity or allergy to treatment additives or diluent substances of dimethyl sulfoxide (DMSO), PlasmaLyte A or human serum albumin (HSA). Please refer to investigational brochure (IB).
  • Patient has active autoimmune disease other than controlled connective tissue disorder or those who are not on active therapy.
  • Patient is immunocompromised, has known human immunodeficiency virus (HIV) positivity, or has actively been treated with immunosuppressive products prior to being infected with SARS-CoV-2.
  • Patient has known active malignancy, unless the Patient has been free of disease for > 3 years from the date of signing the ICF. Exceptions include the following noninvasive malignancies:

    1. Basal cell carcinoma of the skin
    2. Squamous cell carcinoma of the skin
    3. Carcinoma in situ of the cervix
    4. Carcinoma in situ of the breast
    5. Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
  • Detection of other respiratory viruses from mucosal surfaces that would interfere with the study treatment plan.
  • Patient must not have a history of unconsciousness or hemoptysis within 2 weeks of signing informed consent form.

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): NCT04365101


Contacts
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Contact: IDRI (206)858-6013 CYNK-001-COVID-19@idri.org
Contact: Erica Rave, MS (908)845-4338 erica.rave@celularity.com

Locations
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United States, Arizona
Banner University Medical Center Phoenix Recruiting
Phoenix, Arizona, United States, 85006
Contact: Marilyn Glassberg, MD         
Principal Investigator: Marilyn Glassberg, MD         
United States, Arkansas
University of Arkansas Recruiting
Little Rock, Arkansas, United States, 72701
Contact: Mary Burgess, MD         
Principal Investigator: Mary Burgess, MD         
United States, California
UC Irvine Recruiting
Irvine, California, United States, 92697
Contact: Leonid Groysman, MD         
Principal Investigator: Leonid Groysman, MD         
UC Davis Medical Center Recruiting
Sacramento, California, United States, 95817
Contact: Stuart Cohen, MD         
Principal Investigator: Stuart Cohen, MD         
Scripps Health Recruiting
San Diego, California, United States, 92121
Contact: Jason Mason, MD         
Principal Investigator: Jason Mason, MD         
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Michelle Donato, MD         
Principal Investigator: Michelle Donato, MD         
Atlantic Health Recruiting
Morristown, New Jersey, United States, 07960
Contact: Eric D Whitman, MD         
Principal Investigator: Eric D Whitman, MD         
Atlantic Health Recruiting
Summit, New Jersey, United States, 07901
Contact: Eric D Whitman, MD         
Principal Investigator: Eric D Whitman, MD         
United States, Washington
Multicare Health System Recruiting
Tacoma, Washington, United States, 98405
Contact: Vinay Malhotra, MD         
Principal Investigator: Vinay Malhotra, MD         
Sponsors and Collaborators
Celularity Incorporated
IDRI
Lung Biotechnology PBC
California Institute for Regenerative Medicine (CIRM)
Investigators
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Principal Investigator: Corey Casper, MD MPH IDRI
Publications:
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Responsible Party: Celularity Incorporated
ClinicalTrials.gov Identifier: NCT04365101    
Other Study ID Numbers: CYNK-001-COVID-19
First Posted: April 28, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Celularity Incorporated:
CYNK-001
Coronavirus
COVID-19
SARS-Cov-2
cell therapy
NK cells
natural killer cells
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Respiratory Tract Infections
Virus Diseases
Coronavirus Infections
Severe Acute Respiratory Syndrome
Pneumonia, Viral
RNA Virus Infections
Coronaviridae Infections
Nidovirales Infections
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Immune System Diseases