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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: 09 Jun 2021

At a glance

  • Drugs Taniraleucel (Primary)
  • Indications COVID 2019 infections; COVID-19 respiratory infection
  • Focus Adverse reactions; Therapeutic Use
  • Acronyms CYNKCOVID
  • Sponsors Celularity
  • Most Recent Events

    • 14 Apr 2021 According to a Celularity media release, data from this trial will be presented at American Association for Cancer Research (AACR) Annual Meeting 2021.
    • 10 Apr 2021 Results (n=6; till date) of phase I portion of this trial presented at the 112th Annual Meeting of the American Association for Cancer Research
    • 01 Mar 2021 Planned End Date changed from 30 Jun 2021 to 30 Jun 2022.

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 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 6 months

Phase 1 Futility Check for go/no decision to move to Phase 2: Rate of clinical improvement

description: Proportion of patients who improved clinical symptoms as measured by the Ordinal Scale for Clinical Improvement (OSCI)
time_frame: Study Day 15

Phase 2: Time to Clinical Improvement by Ordinal Scale for Clinical Improvement (OSCI)

description: Time to clinical improvement measured by OSCI
time_frame: Study Day 28

Other Endpoints

Rate of Clearance of SARS-CoV-2

description: Proportion of patients with "negative" measurement of COVID-19 by rRT-PCR
time_frame: Study Day 28

Time to Clearance of SARS-CoV-2

description: Time to clearance of SARS-CoV-2 by rRT-PCR testing of mucousal samples with "negative" measurement of COVID-19 by rRT-PCR
time_frame: Study Day 28

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

description: Number and severity of adverse events
time_frame: up to 6 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 6 months

Overall Clinical Benefit by hospital utilization

description: Hospital utilization will be measured as an assessment of overall clinical benefit
time_frame: up to 6 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 6 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 Pulmonary Clearance

description: Proportion of patients who had disappearance of virus from lower respiratory tract infection (LRTI) specimen where it has previously been found.
time_frame: Up to 28 days

Supplemental oxygen-free days

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

Proportion of patients requiring ventilation

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

Duration of hospitalization

description: Time from hospitalization to medical discharge
time_frame: Study Day 28

Radiologic Evaluation Score

description: Chest x-ray and/or CT scan results will be evaluated and scored
time_frame: Study Day 28 and Month 6

All-cause mortality rate

description: Proportion of patients who died
time_frame: Study Day 28 and Month 6

Time to clinical improvement by NEWS2 Score

description: Time to clinical improvement measured by NEWS2 Score
time_frame: Study Day 28

Rate of clinical improvement by NEWS2 Score

description: Proportion of patients who achieved clinical symptom improvement measured by NEWS2 Score
time_frame: Study Day 28 [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -
COVID-19 respiratory infection treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 86

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

Patient Inclusion Criteria

Patient - 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

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.

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 Dec 2021

  • End Dates

    Planned : 30 Jun 2022

Other Details

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

Interventions

Drugs Route Formulation
TaniraleucelPrimary 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.)

Results

Therapeutic efficacy

In early data in the phase I/II CYNKCOVID, treatment with first infusion of taniraleucel demonstrated efficacy in three out of four patients with improvement of oxygenation, inflammatory markers, and radiographic findings [2]

Adverse events

In early data after treatment with taniraleucel in the phase I/II CYNKCOVID was found to be generally well tolerated in all four patients with one Grade 5 event of hypoxic respiratory failure. In the fourth patient, progressive hypoxemia had developed before administration of the first dose of taniraleucel, and required more than 30L of supplemental oxygen delivered by facemask to support a Sp02>90%. After receiving all three doses, the patient refused mechanical ventilation and died of respiratory failure. Attribution to taniraleucel was taken into consideration. Previously, there were no reports of dose-limiting toxicities or evidence of worsening of inflammatory biomarkers observed [2] [3]

Publications

  1. Casper C, Groysman L, Malhotra V, Whitman E, Herb S, Rave E, et al. Early report of 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 (NCT04365101). AACR-2021 2021; abstr. CT201.

    Available from: URL: https://www.abstractsonline.com/pp8/9325/presentation/4812

Authors

Author Total Publications First Author Last Author
Berk G 1 - -
Casper C 1 1 -
Daly C 1 - -
Goman C 1 - -
Groysman L 1 - -
Hariri R 1 - 1
He S 1 - -
Herb S 1 - -
Kang L 1 - -
Koppisetti S 1 - -
Lacasse V 1 - -
Lew A 1 - -
Mahlakoiv T 1 - -
Malhotra V 1 - -
Osokoya S 1 - -
Pecora A 1 - -
Rave E 1 - -
Sagawa Z 1 - -
Thakar M 1 - -
Van der Touw W 1 - -
Whitman E 1 - -
Zhang X 1 - -
Zhu J 1 - -

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Corey Casper, MD MPH IDRI
-
Eric D Whitman, MD Atlantic Health USA
Erica Rave, MS
(908)845-4338 erica.rave@celularity.com
show details
-
IDRI
(206)858-6013 CYNK-001-COVID-19@idri.org
show details
-
Jason Mason, MD Scripps Health USA
Leonid Groysman, MD UC Irvine USA
Marilyn Glassberg, MD Banner University Medical Center Phoenix USA
Mary Burgess, MD University of Arkansas USA
Michelle Donato, MD Hackensack University Medical Center USA
Stuart Cohen, MD UC Davis Medical Center USA
Vinay Malhotra, MD Multicare Health System USA

Centres

Centre Name Location Trial Centre Country
-
-
-
Atlantic Health Morristown, New Jersey USA
Atlantic Health Summit, New Jersey USA
Banner University Medical Center Phoenix Phoenix, Arizona USA
California Institute for Regenerative Medicine (CIRM)
-
-
Celularity
-
-
Hackensack University Medical Center Hackensack, New Jersey USA
IDRI
-
-
Lung Biotechnology PBC
-
-
Multicare Health System Tacoma, Washington USA
Scripps Health San Diego, California USA
UC Davis Medical Center Sacramento, California USA
UC Irvine Irvine, California USA
University of Arkansas Little Rock, Arkansas USA

Trial History

Event Date Event Type Comment
09 Jun 2021 Other trial event Last checked against ClinicalTrials.gov record. Updated 09 Jun 2021
14 Apr 2021 Other trial event According to a Celularity media release, data from this trial will be presented at American Association for Cancer Research (AACR) Annual Meeting 2021. Updated 14 Apr 2021
10 Apr 2021 Results Results (n=6; till date) of phase I portion of this trial presented at the 112th Annual Meeting of the American Association for Cancer Research Updated 24 May 2021
01 Mar 2021 Completion date Planned End Date changed from 30 Jun 2021 to 30 Jun 2022. Updated 04 Mar 2021
01 Mar 2021 Other trial event Planned primary completion date changed from 30 Dec 2020 to 30 Dec 2021. Updated 04 Mar 2021
01 Dec 2020 Other trial event According to a Celularity media release, the company continues to enroll to the next evaluation milestone where the external, independent DMC will review the phase I data for both safety and efficacy.. Updated 09 Dec 2020
01 Dec 2020 Other trial event According to a Celularity media release, the independent Data Monitoring Committee (DMC) completed the first assessment of the trial. The DMC confirmed the absence of dose-limiting toxicities and recommended to move forward with the trial. Additionally, there was no evidence of worsening of inflammatory biomarkers observed. The observed clinical findings justify the continuation of the trial . Updated 09 Dec 2020
11 Sep 2020 Completion date Planned End Date changed from 30 Nov 2021 to 30 Jun 2021. Updated 16 Sep 2020
11 Sep 2020 Other trial event Planned primary completion date changed from 30 Nov 2020 to 30 Dec 2020. Updated 16 Sep 2020
08 Sep 2020 Other trial event According to a Celularity media release, the patient was treated at UC Irvine in California, the first CA site to open for patient enrollment with support from a COVID-19 Project grant awarded to Celularity by the California Institute for Regenerative Medicine (CIRM). Updated 11 Sep 2020
08 Sep 2020 Other trial event According to a Celularity media release, the first patient was dosed in this Phase I/II study of human placental hematopoietic stem cell derived NK cells (CYNK-001) for the treatment of adults with COVID-19 as part of a national clinical trial. Updated 11 Sep 2020
05 Aug 2020 Other trial event According to a Celularity media release, Xiaokui Zhang ( PhD, Chief Scientific Officer) is the Principal Investigator of this study. Updated 10 Aug 2020
05 Aug 2020 Other trial event According to a Celularity media release, the company has received project grant by the California Institute for Regenerative Medicine which will support California Institutions participating in this study. Updated 10 Aug 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 2021;.

    Available from: URL: http://clinicaltrials.gov
  2. Casper C, Groysman L, Malhotra V, Whitman E, Herb S, Rave E, et al. Early report of 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 (NCT04365101). AACR-2021 2021; abstr. CT201.

    Available from: URL: https://www.abstractsonline.com/pp8/9325/presentation/4812
  3. Celularity. Celularity Announces Positive DMC Safety Review and Continuation of its Phase I/II CYNK-001-COVID-19 Study. Media-Rel 2020;.

    Media Release
  4. 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
  5. Celularity. Celularity Doses First Patient in Clinical Trial Evaluating CYNK-001 in COVID-19 Patients. Media-Rel 2020;.

    Media Release
  6. Celularity. Celularity Announces Multiple Presentations at the American Association for Cancer Research (AACR) Annual Meeting 2021. Media-Rel 2021;.

    Media Release
  7. Celularity. Celularity Announces FDA Clearance of IND Application for CYNK-001 in Coronavirus, First in Cellular Therapy. Media-Rel 2020;.

    Media Release
  8. Celularity. Celularity announces the activation of first California Clinical Trial Site following CIRM Grant Award to Advance Treatments for COVID-19. Media-Rel 2020;.

    Media Release
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