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Natural Killer Cell (CYNK-001) Infusions in Adults With COVID-19 (CYNKCOVID)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04365101
Recruitment Status : Active, not recruiting
First Posted : April 28, 2020
Last Update Posted : June 21, 2021
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)
Actual 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, 2021
Estimated Study Completion Date : June 30, 2022

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 Futility Check for go/no decision to move to Phase 2: Rate of clinical improvement [ Time Frame: Study Day 15 ]
    Proportion of patients who improved clinical symptoms as measured by the Ordinal Scale for Clinical Improvement (OSCI)

  3. Phase 2: Time to Clinical Improvement by Ordinal Scale for Clinical Improvement (OSCI) [ Time Frame: Study Day 28 ]
    Time to clinical improvement measured by OSCI


Secondary Outcome Measures :
  1. Rate of Clearance of SARS-CoV-2 [ Time Frame: Study Day 28 ]
    Proportion of patients with "negative" measurement of COVID-19 by rRT-PCR

  2. Time to Clearance of SARS-CoV-2 [ Time Frame: Study Day 28 ]
    Time to clearance of SARS-CoV-2 by rRT-PCR testing of mucousal samples with "negative" measurement of COVID-19 by rRT-PCR

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

  4. 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

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

  6. 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

  7. 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.

  8. 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).

  9. Rate of Pulmonary Clearance [ Time Frame: Up to 28 days ]
    Proportion of patients who had disappearance of virus from lower respiratory tract infection (LRTI) specimen where it has previously been found.

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

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

  12. Duration of hospitalization [ Time Frame: Study Day 28 ]
    Time from hospitalization to medical discharge

  13. Radiologic Evaluation Score [ Time Frame: Study Day 28 and Month 6 ]
    Chest x-ray and/or CT scan results will be evaluated and scored

  14. All-cause mortality rate [ Time Frame: Study Day 28 and Month 6 ]
    Proportion of patients who died

  15. Time to clinical improvement by NEWS2 Score [ Time Frame: Study Day 28 ]
    Time to clinical improvement measured by NEWS2 Score

  16. Rate of clinical improvement by NEWS2 Score [ Time Frame: Study Day 28 ]
    Proportion of patients who achieved clinical symptom improvement measured by NEWS2 Score



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 any symptom/clinical sign of COVID-19 illness or has a positive disease-related chest x-ray/CT scan at screening.
  • 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% on room air; oxygen is permitted as delivered by nasal cannula and/or face mask at any flow rate to achieve this SpO2. Patients must have an SpO2 ≥ 92% if on supplementary oxygen.
  • 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. If clinically indicated, careful consideration should be taken regarding the timing and tapering of high-dose steroids.
  • 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 chronic asthma requiring ongoing medical therapy or other chronic pulmonary disease that, at the discretion of the treating physician, would contraindicate participation in this study.
  • 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; detection of another respiratory virus is not in itself an exclusion criteria unless the investigator believes it would interfere with administration of CYNK-001.
  • Patient must not have a history of unconsciousness or hemoptysis within 2 weeks of signing informed consent form.
  • Patients must not have a history of unconsciousness or hemoptysis within 2 weeks of signing ICF.
  • Patients must not have end stage liver disease and/or cirrhosis.
  • Patient has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
  • Patient has any condition including the presence of laboratory abnormalities which places the patient at unacceptable risk if he or she were to participate in the study.
  • Patient has any condition that confounds the ability to interpret data from the study.

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


Locations
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United States, California
UC Irvine
Irvine, California, United States, 92697
UC Davis Medical Center
Sacramento, California, United States, 95817
Scripps Health
San Diego, California, United States, 92121
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Atlantic Health
Morristown, New Jersey, United States, 07960
Atlantic Health
Summit, New Jersey, United States, 07901
United States, Washington
Multicare Health System
Tacoma, Washington, United States, 98405
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: June 21, 2021
Last Verified: March 2021
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
CYNKCOVID
CYNK-001-COVID-19
Additional relevant MeSH terms:
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Infections
Communicable Diseases
COVID-19
Virus Diseases
Pneumonia
Coronavirus Infections
Respiratory Tract Infections
Severe Acute Respiratory Syndrome
Pneumonia, Viral
RNA Virus Infections
Coronaviridae Infections
Nidovirales Infections
Lung Diseases
Respiratory Tract Diseases
Immune System Diseases
Disease Attributes
Pathologic Processes