Clinical trial NCT04762186: Viable Human SARS-CoV-2 Specific T Cell Transfer in Patients at Risk for Severe COVID-19
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Moderate COVID-19-infection
Keywords: COVID-19
T-Cell
SARS-CoV-2
Infusion
Adoptive
Allogeneic
Lead sponsor: Universitätsklinikum Köln
Sponsor class: OTHER
Collaborators: name: ZKS Köln
name: Hannover Medical School
name: Miltenyi Biomedicine GmbH
First posted: 2021-02-21
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: This trial consist of an open-label dose escalation phase in SARS-CoV-2 infected participants.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Phase I: Dose-limiting toxicities
timeFrame: 28 days
Secondary outcomes:
measure: Phase I: Safety
timeFrame: 3 Month
measure: Phase I: Acute graft- vs. -host disease
timeFrame: 100 days after enrollment
measure: Phase I: Clinical status
timeFrame: 100 days after enrollment
measure: Phase I: Hospitalization
timeFrame: 100 days after enrollment
measure: Phase I: SARS-CoV-2 PCR positivity
timeFrame: 100 days after enrollment
measure: Phase I: Detection of viable human SARS-CoV-2-specific T lymphocyte
timeFrame: 100 days after enrollment
measure: Phase I: viral shedding in nasooropharyngeal swabs
timeFrame: 100 days after enrollment
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: Department I for Internal Medicine University Hospital of Cologne
state: NRW
Study officials:
affiliation: Department I for Internal Medicine University Hospital of Cologne
name: Philipp Köhler, Dr.
role: PRINCIPAL_INVESTIGATOR
References: