poor recruitment

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.

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

During the dose-escalation phase, the study participants and the study team are aware of the treatment as this is an open label trial.