Moderate COVID-19-infection
Conditions
Keywords
COVID-19, T-Cell, SARS-CoV-2, Infusion, Adoptive, Allogeneic
Brief summary
Monocentric open phase I (dose escalation component), followed by a multi-center, randomized, phase II component benchmarking IMP+SoC against SoC
Detailed description
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.
Interventions
DRUGhuman SARS-CoV 2 specific T lymphocytes
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.
Sponsors
ZKS Köln
Hannover Medical School
Miltenyi Biomedicine GmbH
Universitätsklinikum Köln
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
During the dose-escalation phase, the study participants and the study team are aware of the treatment as this is an open label trial.
Intervention model description
This trial consist of an open-label dose escalation phase in SARS-CoV-2 infected participants.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Dose-limiting toxicities | 28 days | Dose-limiting toxicities until Day 28 after infusion of SARS-CoV-2- specific T cells |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Safety | 3 Month | The rate and severity of adverse events after infusion of SARS-CoV-2 specific T cells during the trial |
| Phase I: Acute graft- vs. -host disease | 100 days after enrollment | Clinical manifestations of acute graft- vs. -host disease at day 100 after randomization |
| Phase I: Clinical status | 100 days after enrollment | Clinical status as assessed on the WHO ordinal scale |
| Phase I: SARS-CoV-2 PCR positivity | 100 days after enrollment | Duration of SARS-CoV-2 PCR positivity (in days) from nasooropharyngeal swabs until discharge or death |
| Phase I: Detection of viable human SARS-CoV-2-specific T lymphocyte | 100 days after enrollment | Detection of viable human SARS-CoV-2-specific T lymphocyte after infusion |
| Phase I: viral shedding in nasooropharyngeal swabs | 100 days after enrollment | Effect of viable human SARS-CoV-2-specific T lymphocyte infusion on viral shedding in nasooropharyngeal swabs |
| Phase I: Hospitalization | 100 days after enrollment | duration in days |
Countries
Germany
Outcome results
None listed