Clinical trial NCT04365101: Natural Killer Cell (CYNK-001) Infusions in Adults With COVID-19
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: 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
Keywords: CYNK-001
Coronavirus
COVID-19
SARS-Cov-2
cell therapy
NK cells
natural killer cells
CYNKCOVID
CYNK-001-COVID-19
Lead sponsor: Celularity Incorporated
Sponsor class: INDUSTRY
Collaborators: name: Access to Advanced Health Institute (AAHI)
name: Lung Biotechnology PBC
name: California Institute for Regenerative Medicine (CIRM)
First posted: 2020-04-28
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Phase 1: Frequency and Severity of Adverse Events (AE)
timeFrame: Up to 6 months
measure: Phase 1 Futility Check for go/no decision to move to Phase 2: Rate of clinical improvement
timeFrame: Study Day 15
measure: Phase 2: Time to Clinical Improvement by Ordinal Scale for Clinical Improvement (OSCI)
timeFrame: Study Day 28
Secondary outcomes:
measure: Rate of Clearance of SARS-CoV-2
timeFrame: Study Day 28
measure: Time to Clearance of SARS-CoV-2
timeFrame: Study Day 28
measure: Phase 2: Frequency and Severity of Adverse Events (AE)
timeFrame: up to 6 months
measure: Overall Clinical Benefit by time to medical discharge
timeFrame: up to 6 months
measure: Overall Clinical Benefit by hospital utilization
timeFrame: up to 6 months
measure: Overall Clinical Benefit by measuring mortality rate
timeFrame: up to 6 months
measure: Impact of CYNK-001 on sequential organ failure assessment (SOFA) score
timeFrame: Up to 28 days
measure: Time to Pulmonary Clearance
timeFrame: Up to 28 days
measure: Rate of Pulmonary Clearance
timeFrame: Up to 28 days
measure: Supplemental oxygen-free days
timeFrame: Up to 28 days
measure: Proportion of patients requiring ventilation
timeFrame: Up to 28 days
measure: Duration of hospitalization
timeFrame: Study Day 28
measure: Radiologic Evaluation Score
timeFrame: Study Day 28 and Month 6
measure: All-cause mortality rate
timeFrame: Study Day 28 and Month 6
measure: Time to clinical improvement by NEWS2 Score
timeFrame: Study Day 28
measure: Rate of clinical improvement by NEWS2 Score
timeFrame: Study Day 28
Other outcomes:
Locations:
city: Irvine
country: United States
facility: UC Irvine
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Diego
country: United States
facility: Scripps Health
state: California
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Atlantic Health
state: New Jersey
city: Summit
country: United States
facility: Atlantic Health
state: New Jersey
city: Tacoma
country: United States
facility: Multicare Health System
state: Washington
Study officials:
affiliation: Access to Advanced Health Institute (AAHI)
name: Corey Casper, MD MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F; Chronic Kidney Disease Epidemiology Collaboration. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006 Aug 15;145(4):247-54. doi: 10.7326/0003-4819-145-4-200608150-00004.