CMV Retinitis
Conditions
Keywords
CMV, Retinitis, Virus-specific T cells, Antiviral-resistant CMV, Refractory CMV, Hematopoietic Stem Cell Transplantation, Solid Organ Transplantation, Hematologic malignancy, Autoimmune Disease, Immunosuppressants, Immunosuppressive drugs
Brief summary
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).
Interventions
BIOLOGICALLB-DTK-CMV
LB-DTK-CMV is a CMV-specific T cell therapy product derived from a patient (autologous) 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. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Viral Load | From screening through 24 weeks after treatment initiation | CMV viral load testing is performed using plasma and aqueous humor samples. Viral load is measured at the screening visit and weekly for the first 4 weeks after the first dose in Cycle 1 through the resting period, followed by two measurements at 2-week intervals, then once every 4 weeks, and subsequently once every 12 weeks. |
| Clinical Symptom Assessment | From the screening through 24 weeks after treatment initiation. | Clinical symptom assessments include visual acuity test, fundus examination, and optical coherence tomography. However, optical coherence tomography only applies to patients diagnosed with CMV retinitis involving the central retina. Fluorescein angiography (FAG) may also be performed on Visit 1 and 11 if considered necessary by the investigator. |
| Immunogenicity Testing | From the screening through 24 weeks after treatment initiation. | Immunogenicity testing using IFN-γ ELISpot assay is performed to quantify CMV-specific T cells and evaluate the persistence and reconstitution of the immune response. |
| Adverse Events | From the baseline visit throughout 24 weeks after treatment initiation. | The investigator must confirm the occurrence of adverse events through medical examinations during regular visits throughout the clinical study period. Adverse events shall be assessed at each visit starting from the administration of the investigational drug at the baseline visit (Visit 3). |
Countries
South Korea
Contacts
CONTACTNayoun Kim, Ph.D.
PRINCIPAL_INVESTIGATORYoung Hoon Park, MD-PhD
Department of Ophthalmology, The Catholic University of Korea Seoul St.Mary's Hospital
Outcome results
None listed