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

Phase 1

• Conditions: Coronaviridae Infections; Immunologic Disease; Antiviral Agents; Pneumonia; Virus Disease; Anti-infective Agents; Coronavirus Infection; Respiratory Tract Disease; Respiratory Tract Infections; RNA Virus Infections

• Registration Number: NCT04365101
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-04-22
• Study First Submitted QC: 2020-04-24
• Study First Posted: 2020-04-28
• Study Start: 2020-05-13
• Primary Completion: 2021-12-30
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-24
• Last Update Posted: 2022-05-25
• Study Completion: 2022-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 86

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Phase 2: Time to Clinical Improvement by Ordinal Scale for Clinical Improvement (OSCI)	Study Day 28	Time to clinical improvement measured by OSCI
Phase 1 Futility Check for go/no decision to move to Phase 2: Rate of clinical improvement	Study Day 15	Proportion of patients who improved clinical symptoms as measured by the Ordinal Scale for Clinical Improvement (OSCI)
Phase 1: Frequency and Severity of Adverse Events (AE)	Up to 6 months	Number and severity of adverse events

Secondary Outcome Measures

Name	Time	Method
Overall Clinical Benefit by time to medical discharge	up to 6 months	Time to medical discharge as an assessment of overall clinical benefit
Time to Pulmonary Clearance	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).
Proportion of patients requiring ventilation	Up to 28 days	Proportion of patients who need invasive or non-invasive ventilation
All-cause mortality rate	Study Day 28 and Month 6	Proportion of patients who died
Time to clinical improvement by NEWS2 Score	Study Day 28	Time to clinical improvement measured by NEWS2 Score
Rate of Clearance of SARS-CoV-2	Study Day 28	Proportion of patients with "negative" measurement of COVID-19 by rRT-PCR
Overall Clinical Benefit by measuring mortality rate	up to 6 months	Mortality rate will be measured as an assessment of overall clinical benefit
Radiologic Evaluation Score	Study Day 28 and Month 6	Chest x-ray and/or CT scan results will be evaluated and scored
Time to Clearance of SARS-CoV-2	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
Phase 2: Frequency and Severity of Adverse Events (AE)	up to 6 months	Number and severity of adverse events
Rate of Pulmonary Clearance	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.
Overall Clinical Benefit by hospital utilization	up to 6 months	Hospital utilization will be measured as an assessment of overall clinical benefit
Supplemental oxygen-free days	Up to 28 days	For ventilatory support patients, the days with supplemental oxygen-free.
Rate of clinical improvement by NEWS2 Score	Study Day 28	Proportion of patients who achieved clinical symptom improvement measured by NEWS2 Score
Impact of CYNK-001 on sequential organ failure assessment (SOFA) score	Up to 28 days	Assess the impact of CYNK-001 on changes in sequential organ failure assessment (SOFA) score.
Duration of hospitalization	Study Day 28	Time from hospitalization to medical discharge

Trial Locations

Locations (6)

UC Irvine; 🇺🇸 Irvine, California, United States

UC Davis Medical Center; 🇺🇸 Sacramento, California, United States

Scripps Health; 🇺🇸 San Diego, California, United States

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Atlantic Health; 🇺🇸 Summit, New Jersey, United States

Multicare Health System; 🇺🇸 Tacoma, Washington, United States