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

NCT04365101 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: CYNK-001-COVID-19
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 7

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.

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

Outcome Measures

Primary Outcomes (3)

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

  Number and severity of adverse events

  Up to 6 months

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

  Proportion of patients who improved clinical symptoms as measured by the Ordinal Scale for Clinical Improvement (OSCI)

  Study Day 15

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

  Time to clinical improvement measured by OSCI

  Study Day 28

Secondary Outcomes (16)

• Rate of Clearance of SARS-CoV-2

  Study Day 28

• Time to Clearance of SARS-CoV-2

  Study Day 28

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

  up to 6 months

• Overall Clinical Benefit by time to medical discharge

  up to 6 months

• Overall Clinical Benefit by hospital utilization

  up to 6 months

Study Arms (2)

Phase I

EXPERIMENTAL

CYNK-001 infusions on Days 1, 4, and 7

Biological: CYNK-001

Phase II

ACTIVE COMPARATOR

Randomized, open label; CYNK-001 infusions on Days 1, 4, and 7 compared to Control Group: Best Supportive Care

Biological: CYNK-001

Interventions

CYNK-001 BIOLOGICAL

CYNK-001 is an allogeneic off the shelf cell therapy enriched for CD56+/CD3- NK cells expanded from human placental CD34+ cells.

Phase I; Phase II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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.)
• 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.)
• 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:
• Basal cell carcinoma of the skin
• Squamous cell carcinoma of the skin

Sponsors & Collaborators

• Celularity Incorporated: lead
• Access to Advanced Health Institute (AAHI): collaborator
• Lung Biotechnology PBC: collaborator
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (7)

UC Irvine

Irvine, California, 92697, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

Scripps Health

San Diego, California, 92121, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Atlantic Health

Morristown, New Jersey, 07960, United States

Location

Atlantic Health

Summit, New Jersey, 07901, United States

Location

Multicare Health System

Tacoma, Washington, 98405, United States

Location

Related Publications (1)

• 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.

  PMID: 16908915 BACKGROUND

MeSH Terms

Conditions

Coronavirus Infections; Pneumonia; Pneumonia, Viral; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Immune System Diseases; COVID-19

Condition Hierarchy (Ancestors)

Infections

Study Officials

• Corey Casper, MD MPH

  Access to Advanced Health Institute (AAHI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 22, 2020
• First Posted: April 28, 2020
• Study Start: May 13, 2020
• Primary Completion: December 30, 2021
• Study Completion: June 30, 2022
• Last Updated: May 25, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)