Transfer of Infection Fighting Immune Cells Generated in the Laboratory to High Risk Patients With COVID-19 Infection

NCT04765449 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 21P.015JT 16697
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial will study the safety and efficacy of COVID-19-specific T cells when given as treatment to adult patients (age ≥ 18 years) with a COVID-19 infection. This immunologic treatment is aimed at patients, who are at high risk of progression due to their advanced age, or other underlying health conditions. The outcomes of patients receiving the T cells (Arm A) will be compared to patients treated with standard of care (Arm B).

Conditions

Covid19

Outcome Measures

Primary Outcomes (6)

• Safety of COVID-19-specific CTLs: Infusion Reactions

  Safety will be measured by the absence of: Grade ≥ 3 acute infusion reactions

  Within 48 Hours of CTL Infusion

• Safety of COVID-19-specific CTLs: Grade 4 AEs

  Safety will be measured by the absence of: Any grade 4 or higher adverse event thought to be related to the CTL therapy and outside the spectrum of identified COVID related events.

  Within 14 days of CTL infusion

• Safety of COVID-19-specific CTLs: GVHD

  Safety will be measured by the absence of: Any manifestation of acute GVHD (for acute grades 2-4 GVHD-Glucksberg criteria) 53 resistant to 2 mg/kg of solumedrol or equivalent

  Within 14 days of CTL infusion

• Safety of COVID-19-specific CTLs: Marrow Aplasia

  Safety will be measured by the absence of: Marrow aplasia due to 3rd party engraftment

  Within 14 days of CTL infusion

• Safety of COVID-19-specific CTLs: Neurotoxicty

  Safety will be measured by the absence of: Grade ≥ 2+ Neurotoxicity as measured by the ASTCT/ICANS consensus grading system

  Within 14 days of CTL infusion

• Safety of COVID-19-specific CTLs: CRS

  Safety will be measured by the absence of: Grade ≥ 2+ CRS as measured by the ASTCT Consensus Grading Criteria for CRS

  Within 14 days of CTL infusion

Secondary Outcomes (5)

• Measurement of COVID-19 viral load

  Up to 14 Days

• Studies to detect the persistence of the COVID-19-specific T cells after COVID-19 T cell infusion

  Up to 6 months

• Studies to examine the development of endogenous COVID-19 specific T cells

  Up to 6 months

• Studies to examine the development of anti-COVID-19 antibodies

  Up to 6 months

• Review of medical history including the need for supplemental oxygen, the ability to return to work, performance status, grade of dyspnea, grade of fatigue, survival, the need for blood pressure support

  Up to 6 months

Study Arms (2)

ARM A: Covid-19 Patients Receiving CTLs

EXPERIMENTAL

Patients who have an HLA antigen in common with COVID-19 fighting T cells will receive the COVID-19 T cells. They will be premedicated with diphenhydramine and acetaminophen before the cells are infused intravenously. Close monitoring will continue in the patients' homes for 14 days. Three to six patients will receive a specific dose of T cells, and then if there are no serious side effects, the dose will be increased for the next group of patients. There are 4 doses of T cells to be tested, and each patient will complete a 14 day monitoring period before the next patient can be treated.

Drug: Cytotoxic T Lymphocytes

ARM B: Covid-19 Patients Not Receiving CTLs

NO INTERVENTION

Patients in the observation arm will not have inherited an HLA antigen in common with the COVID-19 T cells and so cannot receive the T cells. They will be monitored by the study staff for the 14 day monitoring period in their homes. They will be taught to record their own blood pressure, temperature, and oxygen level (pulse oximetry) at home and report this information, as well as their progress in getting over the COVID-19 infection, to the study staff every day by phone. The outcomes of patients on arm B will be compared to the outcomes of patients treated on Arm A to see if the T cells made a difference in how patients recovered from COVID-19. Patients in Arm B are not prevented from being treated with any available COVID-19 therapy.

Interventions

Cytotoxic T Lymphocytes DRUG

Given IV. Cytotoxic T Lymphocytes collected from healthy volunteer donors who have recovered from COVID-19. The T cells are collected, manufactured to be COVID-specific, and stored frozen at Thomas Jefferson University.

Also known as: CTLs

ARM A: Covid-19 Patients Receiving CTLs

Eligibility Criteria

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

You may qualify if:

• Have a documented active COVID-19 infection and one of the following high-risk criteria:
• Malignancy receiving radiation or chemotherapy in the prior 24 months.
• Chronic lung disease such as asthma, COPD, interstitial lung disease, pulmonary hypertension or cystic fibrosis, requiring treatment beyond inhaled medications
• Hypertension either treated or with evidence of need for treatment
• Cardiovascular disease requiring active medical monitoring and care including heart failure, heart dysrhythmias, coronary artery disease, congenital heart disease, cardiomyopathy, or pulmonary hypertension
• History of ischemic stroke
• Diabetes (type 1, type 2, or gestational) requiring treatment with insulin or oral hypoglycemics
• Chronic Kidney Disease (Hx of stage 3b or greater as defined by the National Kidney Foundation)
• Chronic Liver Disease (Previously diagnosed with cirrhosis or previously classified as having Pugh-Child class A-C liver disease) oObesity (BMI \>= 35) oSickle Cell Disease or Thalassemia
• Patients requiring nursing home support or who have a Karnofsky Performance Status of 70% or less antedating their COVID-19 illness.
• Age \>= 65 (with or without previously identified comorbid conditions)

You may not qualify if:

• Matching their intended CTL product donor at 5 or 6 of 6 HLA-class I (HLA-A, B, and C) alleles.
• Requiring supplemental oxygen
• Evidence of active COVID-19-related CRS as evidenced by 2 or more of the following characteristics of cytokine storm:
• o\> grade 1 CRS on ASTCT criteria. ASTCT criteria do not provide quantitative guidelines regarding the definition of hypotension. For this trial, hypotension will be defined as:
• requiring vasopressors
• Systolic blood pressure \<90 mm Hg
• Diastolic B/P \< 60 mm Hg NB Lower systolic and diastolic blood pressures will be acceptable if patient's blood pressure is at his/her known baseline.
• Uncontrolled hypertension as defined by a systolic pressure of \> 180 mm Hg or diastolic pressure \> 100 mm Hg. A second blood pressure reading may be obtained by study personnel to assure blood pressure accuracy.
• radiographic studies consistent with adult respiratory distress syndrome
• Patients requiring acute dialysis
• hyperferritinemia as defined by ferritin \> 2000 ng/mL 55
• Concurrent treatment with \>5 mg of prednisone daily (or equivalent).
• Current or ongoing administration of calcineurin inhibitors, chemotherapy, radiation, or other immunosuppressive agents.
• That cannot be held for 14 days after CTL infusion
• That would not decay 3 1/2 half-lives by the day of CTL infusion using longest published half-life.

Sponsors & Collaborators

• Thomas Jefferson University: lead
• Tevogen Bio Inc: collaborator

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (1)

• Grosso D, Wagner JL, O'Connor A, Keck K, Huang Y, Wang ZX, Mehler H, Leiby B, Flomenberg P, Gergis U, Nikbakht N, Morris M, Karp J, Peedin A, Flomenberg N. Safety and feasibility of third-party cytotoxic T lymphocytes for high-risk patients with COVID-19. Blood Adv. 2024 Aug 13;8(15):4113-4124. doi: 10.1182/bloodadvances.2024013344.

  PMID: 38885482 DERIVED

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

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

Study Record Dates

• First Submitted: February 19, 2021
• First Posted: February 21, 2021
• Study Start: September 15, 2021
• Primary Completion: July 29, 2022
• Study Completion: January 19, 2023
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)