Evaluation of Safety and Efficacy of Autologous LB-DTK-CMV in Patients With Antiviral-Resistant and Refractory Cytomegalovirus Retinitis.

An Exploratory Clinical Study of Autologous LB-DTK-CMV in Patients With Antiviral-Resistant and Refractory Cytomegalovirus Retinitis.

The goal of this exploratory clinical study is to evaluate the safety and efficacy of Cytomegalovirus-Specific T cells (LB-DTK-CMV) to treat patients diagnosed with antiviral-resistant and refractory cytomegalovirus retinitis. The main questions it aims to answer are:

• What adverse events occur after the infusion of LB-DTK-CMV?
• What is the duration of efficacy following treatment?
• Is there a clinically significant reduction in CMV viral load in plasma and aqueous humor after the infusion?
• Is there a clinically significant improvement in clinical symptoms after the infusion?

Participants will:

• Receive two infusions of LB-DTK-CMV at 2x10^7cells/m^2 at two-week intervals beginning at the baseline visit (Cycle 1).
• Take a three-week resting period following completion of Cycle 1.
• Receive two infusions of LB-DTK-CMV at 2x10^7cells/m^2 at two-week intervals beginning three weeks after the last dose of Cycle 1 (Cycle 2).

Inclusion Criteria:

1. Patients aged 19 years or older who have been diagnosed with CMV retinitis and have undergone hematopoietic stem cell transplantation or solid organ transplantation for the treatment of hematologic malignancies, or have received high-dose immunosuppressive therapy for the treatment of autoimmune diseases, and who meet at least one of the following criteria:

   • Patients with persistent or progressive CMV retinitis despite systemic antiviral therapy or intravitreal antiviral treatment.
   • Patients who have showed persistent CMV viremia despite systemic antiviral therapy or developed new CMV retinitis.
   • Patients with CMV UL54 or UL97 mutations associated with antiviral resistance.
   • Patients with adverse effects or toxicities limiting the administration of more than one systemic antiviral drug.

2. Patients who are pregnant and able to reduce their steroid dosage to 0.5mg/kg/day of Prednisolone (or an equivalent dose) or less.

3. For women of childbearing potential, those who tested negative on a pregnancy test (blood test) performed on the screening visit.

4. Individuals who have voluntarily decided to participate in this clinical study and have provided written consent to comply with the restrictions.

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

Exclusion Criteria:

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

2. Individuals who meet any of the following criteria at the time of screening:

   • Uncontrolled hypertension

     • Systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite taking antihypertensive medication.

   • Uncontrolled severe diabetes: Severe diabetes is defined as follows:

     • Severe hyperglycemia with HbA1C ≥ 10.0%
     • Individuals who have been hospitalized for diabetic ketoacidosis within the past 12 weeks.
     • Individuals who have received emergency treatment or been hospitalized within the past 12 weeks for severe hypoglycemia (glucose <54 mg/dL) accompanied by seizures and loss of consciousness.

   • Other viral infections

     • Hepatitis B Virus (HBV), Hepatitis C Virus (HCV)
     • However, patients who are tested negative for HBsAg and positive for Anti-HBcAb are not subject to this exclusion criterion.

   • Tuberculosis

   • Syphilis

   • Moderate or severe liver damage

     • Aspartate aminotransferase (AST) or Alanin aminotransferase (ALT) > 5 times the upper limit of normal (ULN)

   • Chronic kidney disease

     • eGFR < 30mL/min/1.73m^2

   • Other uncontrolled infections. However, the following cases are considered controlled infections and do not meet the exclusion criteria:

     • Bacterial infection: Patients must be undergoing definitive antibiotic treatment for the infection and must have shown no signs of progression of the infection for 72 hours prior to enrollment in this clinical study.
     • Fungal infection: Patients must be receiving systemic antifungal therapy and must have shown no signs of infection progression for 1 week prior to enrollment in this clinical study.

3. Patients who have received donor lymphocyte infusion (DLI) within 28 days prior to the scheduled first dose.

4. Patients with active malignant tumor or uncontrolled recurrence.

5. Patients with uncontrolled ophthalmic diseases other than CMV retinitis.

6. Female subjects who are pregnant, breastfeeding, of childbearing potential, or not using appropriate contraceptive methods.

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

8. Patients who have received an investigational product from another clinical study within 24 weeks prior to administration of the investigational product in this study.

9. Patients deemed ineligible for participation in this clinical study by the investigator.