viable human sars-cov-2 specific t cell transfer in patients at risk for severe covid-19

Conditions: Moderate COVID-19-infection

Summary: monocentric open phase i (dose escalation component), followed by a multi-center, randomized, phase ii component benchmarking imp+soc against soc

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.

Eligibility criteria:
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

Keywords: covid-19 t-cell sars-cov-2 infusion adoptive allogeneic