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

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ClinicalTrials.gov Identifier: NCT04765449
Recruitment Status : Not yet recruiting
First Posted : February 21, 2021
Last Update Posted : July 26, 2021
Sponsor:
Collaborator:
Tevogen Bio Inc
Information provided by (Responsible Party):
Thomas Jefferson University

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).

Condition or disease Intervention/treatment Phase
Covid19 Drug: Cytotoxic T Lymphocytes Phase 1

Detailed Description:
T cells that recognize COVID-19 peptides will be manufactured at Thomas Jefferson University and are frozen and ready for use. The T cells have to have an immune protein called HLA in common with a patient to work. If a patient enrolled on the COVID-19 study has this HLA, they will receive a dose of the COVID-19 T cells. Groups of 3-6 patients will be treated at each testing dose level. There are four dose levels of T cells: 1 x 105/kg, 3 x 105/kg, 1 x 106/kg, and 3 x 106/kg. Patients will receive the T cells intravenously in the hospital and be monitored there for 4 days before being discharged. Before discharge, patients will be taught to take and record their temperature, blood pressure, and oxygen levels (using a finger monitor) at home. After discharge, study staff will continue to monitor patient symptoms and recordings with video visits or phone calls daily until the monitoring period of 14 days is over. Patients will also be asked to give blood samples 7, 14, 28, days and 2, 3, and 6 months after the T cells are given. Patients who meet study criteria and wish to participate but do not have the HLA protein in common with the T cells, will be monitored by study personnel in their own homes for the full 14 day period. These patients will also be taught to take and record their temperature, blood pressure, and oxygen level. Study personnel will contact them daily by video or voice calls and check on the results of their readings and their symptoms. These patients may be treated with any standard or experimental COVID-19 therapy. How patients handle their COVID-19 infection will be compared between the group of people receiving the T cells and the group of people who do not receive the T cells.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Third-Party COVID-19-Specific Cytotoxic T Lymphocytes for the Treatment of Elderly and High-Risk Patients With COVID-19 Infection
Estimated Study Start Date : July 19, 2021
Estimated Primary Completion Date : July 29, 2022
Estimated Study Completion Date : July 29, 2022

Arm Intervention/treatment
Experimental: ARM A: Covid-19 Patients Receiving CTLs
Patients who have an HLA antigen in common with COVID-19 fighting T cells will be admitted to the hospital and receive the COVID-19 T cells. They will be premedicated with diphenhydramine and acetaminophen before the cells are infused intravenously. The patients will be monitored for side effects for at least 4 days prior to discharge. 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
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.
Other Name: CTLs

No Intervention: ARM B: Covid-19 Patients Not Receiving CTLs
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.



Primary Outcome Measures :
  1. Safety of COVID-19-specific CTLs: Infusion Reactions [ Time Frame: Within 48 Hours of CTL Infusion ]
    Safety will be measured by the absence of: Grade ≥ 3 acute infusion reactions

  2. Safety of COVID-19-specific CTLs: Grade 4 AEs [ Time Frame: Within 14 days of CTL infusion ]
    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.

  3. Safety of COVID-19-specific CTLs: GVHD [ Time Frame: Within 14 days of CTL infusion ]
    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

  4. Safety of COVID-19-specific CTLs: Marrow Aplasia [ Time Frame: Within 14 days of CTL infusion ]
    Safety will be measured by the absence of: Marrow aplasia due to 3rd party engraftment

  5. Safety of COVID-19-specific CTLs: Neurotoxicty [ Time Frame: Within 14 days of CTL infusion ]
    Safety will be measured by the absence of: Grade ≥ 2+ Neurotoxicity as measured by the ASTCT/ICANS consensus grading system

  6. Safety of COVID-19-specific CTLs: CRS [ Time Frame: Within 14 days of CTL infusion ]
    Safety will be measured by the absence of: Grade ≥ 2+ CRS as measured by the ASTCT Consensus Grading Criteria for CRS


Secondary Outcome Measures :
  1. Measurement of COVID-19 viral load [ Time Frame: Up to 14 Days ]
    Patients will have blood drawn, nasal (not nasopharyngeal) specimens collected

  2. Studies to detect the persistence of the COVID-19-specific T cells after COVID-19 T cell infusion [ Time Frame: Up to 6 months ]
    Patients will have blood drawn, nasal (not nasopharyngeal) specimens collected

  3. Studies to examine the development of endogenous COVID-19 specific T cells [ Time Frame: Up to 6 months ]
    Patients will have blood drawn, nasal (not nasopharyngeal) specimens collected

  4. Studies to examine the development of anti-COVID-19 antibodies [ Time Frame: Up to 6 months ]
    Patients will have blood drawn, nasal (not nasopharyngeal) specimens collected

  5. 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 [ Time Frame: Up to 6 months ]
    Patients will have their medical course followed by the study team



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Have a documented active COVID-19 infection and one of the following high-risk criteria:

  • Malignancy receiving radiation or chemotherapy in the prior 12 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 >= 70 (with or without previously identified comorbid conditions)

Exclusion Criteria:

  • 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:

    1. requiring vasopressors
    2. Systolic blood pressure <110 mm Hg
    3. Diastolic B/P < 70 mm Hg NB Lower systolic and diastolic blood pressures will be acceptable if patient's blood pressure is at his/her known baseline.

      oUncontrolled hypertension as defined by a systolic pressure of > 160 mm Hg or diastolic pressure > 95 mm Hg. A second blood pressure reading may be obtained by study personnel to assure blood pressure accuracy.

      oradiographic studies consistent with adult respiratory distress syndrome oPatients requiring acute dialysis ohyperferritinemia as defined by ferritin > 2000 ng/mL 55 oConcurrent treatment with >5 mg of prednisone daily (or equivalent).

  • Current or ongoing administration of calcineurin inhibitors, chemotherapy, radiation, or other immunosuppressive agents.
  • Receipt of agents with ongoing immunosuppressive properties in the last 30 days including, ATG, Alemtuzumab, or similar agents.
  • Prior bone marrow, stem cell, or solid organ transplant
  • Active HIV infection with CD4 count less than 200/ul.
  • Known autoimmune disease requiring systemic treatment.
  • Pregnancy (lactating females allowable)
  • Concomitant treatment with another experimental intervention for COVID-19 other than Remdesivir.
  • History of allergic reaction to cellular therapy products (includes blood transfusion), diphenhydramine, or tocilizumb
  • Corrected QT interval > 450 milliseconds
  • History of torsade de pointes or other ventricular arrhythmia Women of childbearing potential, and partners of women of childbearing potential should be using at least one method of highly effective contraception at the time of enrollment and for the 14-day duration of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04765449


Contacts
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Contact: Dolores Grosso, DNP 215-955-8874 Dolores.Grosso@jefferson.edu

Locations
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United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
Thomas Jefferson University
Tevogen Bio Inc
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Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT04765449    
Other Study ID Numbers: 21P.015
First Posted: February 21, 2021    Key Record Dates
Last Update Posted: July 26, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infection