Evaluation of Safety, Tolerance, and Efficacy of Allogeneic LB-DTK-COV19 in Severe Coronavirus Disease 2019 Patients

A Single Center, Open-Label, Phase I Study to Evaluate the Safety, Tolerance, and Efficacy of Allogeneic LB-DTK-COV19 Cells in Severe Coronavirus Disease 2019 Patients

The goal of this clinical trial is to evaluate the safety, tolerability, and efficacy of allogeneic SARS-CoV-2-Specific T cells (LB-DTK-COV19) in patients with persistent clinical symptoms following a positive SARS-CoV-2 PCR test for 14 days or longer. The main questions it aims to answer are:

• What is the maximum tolerated dose of LB-DTK-COV19 based on dose-limiting toxicity?
• What treatment emergent adverse events occur following LB-DTK-COV19 infusion?
• Does LB-DTK-COV19 result in clinically significant improvement or worsening of clinical symptoms following infusion?

Participants will:

• Receive a single intravenous infusion of LB-DTK-COV19 (low dose: 5x10^6/m^2; mid dose:1x10^7/m^2; high dose: 2x10^7/m^2).
• Attend follow-up visits at the clinic for 6 months after the infusion.

Inclusion Criteria:

1. Adults aged 19 years or older at the time of screening (Visit 1).

2. Individuals confirmed positive for COVID-19 by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) testing. If the test was conducted more than 10 days prior to the screening date, retesting is required for enrollment. The testing criteria follow the "Guidelines for Laboratory Diagnosis of COVID-19".

3. Individuals who have received treatment with two or more antiviral drugs.

4. Patients who are refractory to standard-of-care.

5. Individuals who meet all the following criteria of persistent COVID-19:

   • Viral Criteria: Positive COVID-19 PCR test results persisting for more than 14 days after the initial positive test

   • Clinical Criteria: Individuals with two or more of the following symptoms for 14 days or more either intermittently or continuously

     • Fever
     • Fatigue
     • Respiratory symptoms
     • Weight loss
     • Diarrhea
     • Increase in inflammatory markers

   • Imaging Criteria: Clinically significant change in lung parenchyma based on chest CT.

   • Medical History Criteria: Individuals who meet any of the following criteria

     • Administered CD20 inhibitor in the past 1 year
     • Hematologic malignancies (ex. CLL, MM, NHL, etc)
     • Undergone hematopoietic stem cell transplantation or GVHD treatment in the past 1 year
     • Undergone CAR-T therapy
     • Solid organ transplant patients
     • Primary hypogammaglobulinemia
     • Other severe primary or acquired immunodeficiency

6. Female participants or male participants with female partners who agree to maintain the following contraception methods during the clinical trial period, and who meet one of the following criteria:

   • The female participant or the female partner of the male participant is postmenopausal (defined as non-therapy-induced amenorrhea for 12 months or more, or as medically confirmed menopause)

   • The female participant or the female partner of the male participant is infertile due to surgical sterilization (ex. removal of ovaries and/or uterus)

   • Agrees to absolute abstinence during the clinical trial period [For female participants, intermittent abstinence (ex. ovulation timing, symptom-based temperature monitoring, or withdrawal methods) is not considered as agreeing to abstinence]

   • If the female participant or the female partner of the male participant is a woman of childbearing potential (WOCBP) who has not undergone sterilization surgery, one of the following contraception methods must be used:

     • Hormonal methods (implant, patch, oral contraceptives)
     • Intrauterine device
     • Dual barrier methods (simultaneous use of two methods, such as male condoms, female condoms, cervical caps, diaphragms, or contraceptive sponges)

7. For women of childbearing potential or women who are less than 12 months postmenopausal, a negative pregnancy test (blood test) confirmed at the screening visit.

8. Individuals who have at least one HLA match with the investigational drug in MHC class I.

9. Individuals who voluntarily agree to participate in this clinical trial and provide written consent to comply with the restrictions.

10. Individuals deemed suitable as study subjects through screening tests (vital signs, physical examination, medical and surgical history, electrocardiogram, laboratory tests, etc).

Exclusion Criteria:

1. Severely ill patients who meet the following criteria:

   • Requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
   • Acute respiratory distress syndrome (ARDS), shock, or multiple organ failure

2. Uncontrolled pulmonary diseases other than COVID-19 pneumonia (ex. chronic obstructive pulmonary disease, asthma, cystic fibrosis, tuberculosis, etc.)

3. Patients requiring intubation, mechanical ventilation (WHO 8-OS stage 6), or ECMO (stage 7) at the time of screening.

4. Individuals who have received treatment with ATG (Antithymocyte Globulin), Campath, or other T-cell immunosuppressive monoclonal antibodies within 28 days prior to the screening visit.

5. Patients with uncontrollable hypertension, uncontrollable diabetes, other viral infections (ex. Human immunodeficiency virus (HIV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), etc), syphilis, refractory malignancy, moderate or severe liver damage [Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 5 Lab normal range (LNR)], or chronic kidney diseases (estimated Glomerular filtration rate (eGFR) < 30 mL/min/1.73m^2) based on medical history or at the time of screening.

   • Uncontrollable hypertension is defined as Systolic BP ≥160mmHg or Diastolic BP ≥100 mmHg despite taking blood pressure medications (Up to 3 measurements with a minimum interval of 5 minutes)

   • Severe diabetes is defined as follows:

     1. Severe hyperglycemia with HbA1c ≥ 10.0%
     2. Individuals who have been hospitalized for diabetic ketoacidosis within the past 12 weeks
     3. Individuals who have received emergency treatment or been hospitalized within the past 12 weeks for severe hypoglycemia (glucose < 54mg/dL) accompanied by seizures and loss of consciousness

6. Patients with a history of substance abuse within 6 months prior to the administration of the investigational product, or those suspected of taking drugs prone to misuse based on medical interviews and physical examinations.

7. Patients who require vasopressors.

8. Patients with a history of hypersensitivity to T-cell therapy.

9. Patients with a history of autoimmune diseases.

10. Patients with hemophilia or receiving anticoagulant therapy who are at significant risk of bleeding during injection.

11. Patients who participated in another clinical study within 24 weeks prior to the administration of the investigational product.

12. Patients with a life expectancy of less than 24 hours at the time of screening.

13. Other patients deemed unsuitable for participation in this clinical trial by the investigator.