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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

Trial Profile

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

Status: Recruiting
Phase of Trial: Phase I/II

Latest Information Update: 28 May 2020

At a glance

  • Drugs CYNK 001 (Primary)
  • Indications COVID 2019 infections; Severe acute respiratory syndrome
  • Focus Adverse reactions; Therapeutic Use
  • Acronyms CYNK001COVID
  • Sponsors Celularity
  • Most Recent Events

    • 15 May 2020 Status changed from not yet recruiting to recruiting.
    • 24 Apr 2020 Status changed from planning to not yet recruiting.
    • 06 Apr 2020 New trial record

Trial Overview

Purpose

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 hospitalized patients with moderate COVID-19 disease.

Primary Endpoints

Phase 1: Frequency and Severity of Adverse Events (AE)

description: Number and severity of adverse events
time_frame: Up to 12 months

Time to Clearance of SARS-CoV-2

description: Time from the date of randomization to the clearance of SARS-CoV-2 by rRT-PCR
time_frame: Up to 12 months

Rate of Clearance of SARS-CoV-2

description: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR
time_frame: Up to 12 months

Time to Clinical Improvement of cough

description: Time from the date of randomization to the first date of clinical improvement of cough.
time_frame: Up to 28 days

Time to Clinical Improvement of fever

description: Time from the date of randomization to the first date of clinical improvement of fever
time_frame: Up to 28 days

Time to Clinical Improvement in radiological evaluation of disease related chest x-ray

description: Time from the date of randomization to the first date of clinical improvement of radiological evaluation of disease related chest x-ray
time_frame: Up to 28 days

Rate of Clinical Improvement of fever

description: Proportion of subjects who achieved clinical improvement of fever
time_frame: Up to 28 days

Rate of Clinical Improvement of cough

description: Proportion of subjects who achieved clinical improvement of cough
time_frame: Up to 28 days

Rate of Clinical Improvement of radiological evaluation of disease related chest x-ray

description: Proportion of subjects who achieved clinical improvement of radiological evaluation of disease related chest x-ray
time_frame: Up to 28 days

Time to Pulmonary Clearance

description: 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).
time_frame: Up to 28 days

Rate of Pulmonary Clearance

description: Proportion of subjects who achieve pulmonary clearance
time_frame: Up to 28 days

Impact of CYNK-001 on sequential organ failure assessment (SOFA) score

description: Assess the impact of CYNK-001 on changes in sequential organ failure assessment (SOFA) score.
time_frame: Up to 28 days

Other Endpoints

Phase 2: Frequency and Severity of Adverse Events (AE)

description: Number and severity of adverse events time_frame: up to 12 months

Overall Clinical Benefit by time to medical discharge

description: Time to medical discharge as an assessment of overall clinical benefit time_frame: up to 12 months

Overall Clinical Benefit by hospital utilization

description: Hospital utilization will be measured as an assessment of overall clinical benefit time_frame: up to 12 months

Overall Clinical Benefit by measuring mortality rate

description: Mortality rate will be measured as an assessment of overall clinical benefit time_frame: up to 12 months

Impact of CYNK-001 on sequential organ failure assessment (SOFA) score

description: Assess the impact of CYNK-001 on changes in sequential organ failure assessment (SOFA) score. time_frame: Up to 28 days

Time to Pulmonary Clearance

description: 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). time_frame: Up to 28 days

Rate of Clinical Improvement of cough

description: Proportion of subjects who achieved clinical improvement of cough time_frame: Up to 28 days

Supplemental oxygen-free days

description: For ventilatory support subjects, the days with supplemental oxygen-free. time_frame: Up to 28 days

Proportion of subjects requiring ventilation

description: Proportion of subjects who need invasive or non-invasive ventilation time_frame: Up to 28 days

Rate of Clearance of SARS-CoV-2

description: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR time_frame: Up to 12 months [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -
Severe acute respiratory syndrome treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 86

  • Sex male & female
  • Age Group ≥ 18 years; adult

Patient Inclusion Criteria

Patient 1. Patient has confirmed positivity for SARS-CoV-2 as measured by rRT-PCR. 2. Patient is experiencing at least 2 of the 3 symptoms of the list below: 1. Fever ≥ 38 °C 2. Cough 3. Positive disease-related chest x-ray 3. Patient is ≥ 45 years of age and at least one co-morbidity (Cardiovascular disease, Hypertension, diabetes, Respiratory disease etc.) at the time of signing the Study informed consent form (ICF) for the Phase I of the study. 4. Patient is ≥ 18 years of age at the time of signing the Study ICF for the Phase II of the study. 5. Patient understands and voluntarily signs the Study ICF prior to any study-related assessments/procedures are conducted. 6. Patient has mild to moderate pulmonary involvement as measured by chest radiograph presenting with lower respiratory tract infection. 7. Patient with mild to moderate severity of inflammation which is no greater than Grade 1 Cytokine Release Syndrome (CRS) at baseline is permitted. 8. Hospital admission for start of treatment period. 9. Patient is able to receive treatment with antibiotic agents as prescribed by the treating physician using medical judgement. 10. SpO2 >92% on room air. 11. 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. 12. 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. a. *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). 13. 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

Patient Exclusion Criteria

1. Patient not formally admitted to the hospital. 2. Patient admitted to Intensive Care Unit / Pulmonary Acute Care Unit designated area with severe pulmonary pneumonia, ARDS or Sepsis. 3. Patient anticipated to be transferred to another hospital within 96 hours of first CYNK-001 treatment. 4. Patient is pregnant or breastfeeding. 5. Patient has a history of severe asthma and is presently on chronic medications or has a history of other symptomatic pulmonary disease. 6. Patient has been treated with antiviral therapy for COVID-19 symptoms within 7 days of signing ICF. 7. Patient is receiving antiviral therapy with known or suspected activity against COVID-19 including remdesivir, lopinavir/ritonavir, sofosbuvir, or ribavirin at time of hospital admission. 8. 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. 9. 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). 10. 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. 11. Patient has active autoimmune disease other than controlled connective tissue disorder or those who are not on active therapy. 12. 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. 13. 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) 14. Detection of other respiratory viruses from mucosal surfaces that would interfere with the study treatment plan.

Trial Details

Identifiers

Identifier Owner
NCT04365101 ClinicalTrials.gov: US National Institutes of Health
CYNK001COVID19 -

Organisations

  • Sponsors Celularity
  • Affiliations Celularity; Lung Biotechnology; Sorrento Therapeutics

Trial Dates

  • Initiation Dates

    Planned : 30 Apr 2020

    Actual : 13 May 2020

  • Primary Completion Dates

    Planned : 30 Nov 2020

  • End Dates

    Planned : 30 Nov 2021

Other Details

  • Design open; prospective; randomised; sequential
  • Phase of Trial Phase I/II
  • Location USA
  • Focus Adverse reactions; Therapeutic Use

Interventions

Drugs Route Formulation
CYNK 001Primary Drug Intravenous Infusion

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.)

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.)

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Corey Casper, MD MPH IDRI
-
Erica Rave, MS
(908)845-4338 erica.rave@celularity.com
show details
-
IDRI
(206)858-6013 CYNK-001-COVID-19@idri.org
show details
-
Michelle Donato, MD Hackensack University Medical Center USA
Vinay Malhotra, MD Multicare Health System USA

Centres

Centre Name Location Trial Centre Country
-
-
-
Celularity
-
-
Hackensack University Medical Center Hackensack, New Jersey USA
IDRI
-
-
Lung Biotechnology PBC
-
-
Multicare Health System Tacoma, Washington USA

Trial History

Event Date Event Type Comment
28 May 2020 Other trial event Last checked against ClinicalTrials.gov: US National Institutes of Health record. Updated 28 May 2020
15 May 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 20 May 2020
29 Apr 2020 Other trial event New source identified and integrated ClinicalTrials.gov: (US National Institutes of Health: NCT04365101). Updated 29 Apr 2020
24 Apr 2020 Status change - not yet recruiting Status changed from planning to not yet recruiting. Updated 29 Apr 2020
06 Apr 2020 New trial record New trial record Updated 06 Apr 2020
02 Apr 2020 Other trial event According to a Sorrento Therapeutics, Inc. media release, the company will make available to Celularity current existing capacity in Sorrento's state-of-the-art cGMP cell therapy manufacturing facilities.The addition of Sorrento's cGMP cell therapy manufacturing capacity is expected to facilitate the rapid scale-up and sustained production of Celularity's novel CYNK-001 cell therapy for use in its Phase I/II clinical study in COVID-19 infected adults. Updated 09 Apr 2020
02 Apr 2020 Status change - recruiting Status changed from planning to recruiting. Updated 09 Apr 2020
02 Apr 2020 Other trial event According to a Celularity media release, the U.S. Food and Drug Administration (FDA) has cleared the Company's Investigational New Drug (IND) application for the use of CYNK-001 in adults with COVID-19. Updated 09 Apr 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. Celularity. Celularity Announces FDA Clearance of IND Application for CYNK-001 in Coronavirus, First in Cellular Therapy. Media-Rel 2020;.

    Media Release
  3. Sorrento Therapeutics. SORRENTO TO PROVIDE MANUFACTURING SUPPORT TO CELULARITY AS CYNK-001 NK CELL TRIAL FOR COVID-19 BEGINS ENROLLING PATIENTS. Media-Rel 2020;.

    Media Release
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