COVID-19, COVID-19 (SARS-CoV-2 Infection)
Conditions
Keywords
SARS-CoV-2 Infection, Infections, Virus Diseases, Respiratory Symptoms, Hematopoietic Stem Cell Transplantation, Immunocompromised host, Pneumonia, Hematologic Malignancies
Brief summary
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.
Interventions
BIOLOGICALLB-DTK-COV19
LB-DTK-COV19 is an allogeneic SARS-CoV-2-specific T cell therapy product derived from third-party donors and is stored frozen in a colorless, transparent freeze-dried vial until thawed into liquid before administration.
Sponsors
LucasBio
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NCI-CTCAE v5.0 ≥ Grade 3 Rate | From baseline visit through 24 weeks after treatment initiation. | The incidence rate of Grade 3 or higher adverse events, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), is assessed to evaluate the safety of LB-DTK-COV19. Grade 3-5 adverse events include severe or medically significant, life-threatening, and fatal adverse events. |
| Adverse Events | From the baseline visit through 24 weeks after treatment initiation. | The investigator must confirm the occurrence of adverse events through medical examinations, including interviews and medical history reviews, during regular visits throughout the clinical trial period. Adverse events shall be assessed at each visit starting from the administration of the investigational drug at the baseline visit. |
| Disease Progression Rate | From the screening visit through 24 weeks after treatment initiation. | Proportion of patients with disease progression (defined as the need for mechanical ventilation, extracorporeal membrane oxygenation \[ECMO\], or death) at 1 month following LB-DTK-COV19 administration. |
| WHO Ordinal Scale | From the screening visit through 24 weeks after treatment initiation. | The time to improvement in the World Health Organization (WHO) Ordinal Scale, defined as an improvement of at least 1 point from baseline, will be assessed. The WHO Ordinal Scale ranges from 0 (uninfected, with no viral RNA detected) to 10 (death), with higher scores indicating greater disease severity. The outcome is summarized by both the time to improvement and the proportion of participants achieving the improvement by four weeks following LB-DTK-COV19 infusion. |
| NEWS2 Score | From the screening visit through 24 weeks after treatment initiation. | The time to achievement of a National Early Warning Score 2 (NEWS2) of 0 sustained for at least 24 hours is assessed. The NEWS2 score ranges from 0 (requiring routine monitoring) to 20 (emergent transport to hospital), with higher scores indicating greater degree of illness of a patient. The outcome is summarized by both the time to achievement and the proportion of participants achieving the endpoint by four weeks following LB-DTK-COV19 infusion. |
| Viral load | From the screening visit through 24 weeks after treatment initiation. | Nasopharyngeal swab samples were used for PCR testing to assess SARS-CoV-2 viral load. |
| SARS-CoV2-Specific T-cell Responses | From the screening visit through 24 weeks after treatment initiation. | SARS-CoV2-specific T-cell responses are assessed using IFN-γ ELISPOT assay and spot-forming units. |
| Characterization of SARS-CoV-2-Specific T cells | From the screening visit through 24 weeks after treatment initiation. | SARS-CoV-2-specific T cell subsets are characterized using flow cytometry. |
Countries
South Korea
Contacts
PRINCIPAL_INVESTIGATORDong-Gun Lee, MD-PhD
Department of Infectious Disease, The Catholic University of Korea Seoul St.Mary's Hospital
Outcome results
None listed