Viable Human SARS-CoV-2 Specific T Cell Transfer in Patients at Risk for Severe COVID-19

Study Overview
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Brief Summary
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Monocentric open phase I (dose escalation component), followed by a multi-center, randomized, phase II component benchmarking IMP+SoC against SoC

Detailed Description
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The clinical trial will consist of a phase I and a phase II part. The main trial objective in the phase I part is to determine the recommended phase II dose (RP2D) of viable human SARS-CoV 2-specific T cells by evaluation of safety and tolerability. In the phase II part, the primary objective is to gain first data on efficacy of adaptive therapy with viable human SARS-CoV-2-specific T cells. This will be a randomized, prospective feasibility trial. Details to phase II will be updated after completion of phase I.

Official Title
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A Phase I/ Randomized Phase II Trial to Analyse Safety and Efficacy of Human SARS-CoV-2-specific T Lymphocyte Transfer in Patients With COVID-19 in Need of Treatment or at Risk of Severe COVID-19

Conditions
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Moderate COVID-19-infection

Intervention / Treatment
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* Drug: human SARS-CoV 2 specific T lymphocytes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or above Written informed consent from the trial subject has been obtained Willing to follow contraception guidelines Tested positive for SARS-CoV-2 by PCR <72 hours after swab A maximum of 14 days between onset of symptoms and enrollment WHO score 5 OR WHO score 4 with at least one additional risk factor for disease progression Acceptable risk factors are: Radiographically proven lung infiltrates Immunosuppression either by malignant disease or it's treatment, or other underlying diseases leading to immunodeficiency or underlying diseases that require treatment resulting in immunosuppression Immunosuppressive drugs or steroids at a prednisolone equivalent of <1 mg/kg BW) Receipt of an autologous transplant within the last 5 years Receipt of an allogeneic transplant within the last 5 years or ongoing immunosuppression Exclusion criteria: Participation in any other clinical trial of an experimental agent treatment Active GvHD or history of GvHD History of CAR-T-Cell Therapy COVID-19 WHO ordinal scale ≥6 Anticipated life-expectancy <72 hours Expected duration of hospital stay <72 hours Sepsis-induced leukopenia or thrombocytopenia (leukocytes <1,000/µl or platelets <50,000/µl). If the cytopenias result from underlying hematologic disease or its treatment this will not be regarded as exclusion criterion CT pneumonia score ≥13 [50] Any Steroids ≥1 mg/kg Prednisolon-equivalent/kg BW, besides 6 mg Dexamethasone i.v. or p.o. 1x/d as SoC for COVID-19 Pregnant or breast feeding Any serious medical condition or abnormality of clinical laboratory tests that, in the Investigator's judgment, precludes the subject's safe participation in and completion of the study Therapeutic donor lymphocyte infusion (DLI) less than 100 days prior to IMP infusion Known hypersensitivity to iron dextran Known pre-existing human anti-mouse antibodies (HAMAs) ontraindication against mandatory protocol-inherent comedication(s): antihistamine and/or acetaminophen Failure to use highly-effective contraceptive methods. The following contraceptive methods with a Pearl Index lower than 1% are regarded as highly-effective: Oral hormonal contraception ('pill') Dermal hormonal contraception Vaginal hormonal contraception (NuvaRing®) Contraceptive plaster Long-acting injectable contraceptives Implants that release progesterone (Implanon®) Tubal ligation (female sterilization) Intrauterine devices that release hormones (hormone spiral) Double barrier methods This means that the following are not regarded as safe: condom plus spermicide, simple barrier methods (vaginal pessaries, condom, female condoms), copper spirals, the rhythm method, basal temperature method, and the withdrawal method (coitus interruptus). Persons with any kind of dependency on the principal investigator or employed by the sponsor or principal investigator Legally incapacitated persons Persons held in an institution by legal or official order

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: This trial consist of an open-label dose escalation phase in SARS-CoV-2 infected participants.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation<br>SARS CoV-2 infected participants will receive a single infusion over 15 to 30 minutes | Drug: human SARS-CoV 2 specific T lymphocytes<br>* In dose level one, SARS-CoV-2 infected patients will receive 1,000 viable human SARS CoV-2 specific T lymphocytes per kg BW. In dose level two SARS-CoV-2 infected patients will receive 5,000 viable human SARS CoV-2 specific T lymphocytes per kg BW. In parallel, all patients will receive the current SoC treatment for COVID-19.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Dose-limiting toxicities | Dose-limiting toxicities until Day 28 after infusion of SARS-CoV-2- specific T cells | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Safety | The rate and severity of adverse events after infusion of SARS-CoV-2 specific T cells during the trial | 3 Month | 
| Phase I: Acute graft- vs. -host disease | Clinical manifestations of acute graft- vs. -host disease at day 100 after randomization | 100 days after enrollment | 
| Phase I: Clinical status | Clinical status as assessed on the WHO ordinal scale | 100 days after enrollment | 
| Phase I: Hospitalization | duration in days | 100 days after enrollment | 
| Phase I: SARS-CoV-2 PCR positivity | Duration of SARS-CoV-2 PCR positivity (in days) from nasooropharyngeal swabs until discharge or death | 100 days after enrollment | 
| Phase I: Detection of viable human SARS-CoV-2-specific T lymphocyte | Detection of viable human SARS-CoV-2-specific T lymphocyte after infusion | 100 days after enrollment | 
| Phase I: viral shedding in nasooropharyngeal swabs | Effect of viable human SARS-CoV-2-specific T lymphocyte infusion on viral shedding in nasooropharyngeal swabs | 100 days after enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, T-Cell, SARS-CoV-2, Infusion, Adoptive, Allogeneic