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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04762186
Recruitment Status : Recruiting
First Posted : February 21, 2021
Last Update Posted : December 20, 2021
Sponsor:
Collaborators:
ZKS Köln
Hannover Medical School
Miltenyi Biomedicine GmbH
Information provided by (Responsible Party):
Universitätsklinikum Köln

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

Condition or disease Intervention/treatment Phase
Moderate COVID-19-infection Drug: human SARS-CoV 2 specific T lymphocytes Phase 1

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: This trial consist of an open-label dose escalation phase in SARS-CoV-2 infected participants.
Masking: None (Open Label)
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.
Primary Purpose: Treatment
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
Actual Study Start Date : December 8, 2021
Estimated Primary Completion Date : February 1, 2023
Estimated Study Completion Date : February 1, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Dose escalation
SARS CoV-2 infected participants will receive a single infusion over 15 to 30 minutes
 Drug: human 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.


Outcome Measures
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Primary Outcome Measures :
  1. Phase I: Dose-limiting toxicities [ Time Frame: 28 days ]
    Dose-limiting toxicities until Day 28 after infusion of SARS-CoV-2- specific T cells


Secondary Outcome Measures :
  1. Phase I: Safety [ Time Frame: 3 Month ]
    The rate and severity of adverse events after infusion of SARS-CoV-2 specific T cells during the trial

  2. Phase I: Acute graft- vs. -host disease [ Time Frame: 100 days after enrollment ]
    Clinical manifestations of acute graft- vs. -host disease at day 100 after randomization

  3. Phase I: Clinical status [ Time Frame: 100 days after enrollment ]
    Clinical status as assessed on the WHO ordinal scale

  4. Phase I: Hospitalization [ Time Frame: 100 days after enrollment ]
    duration in days

  5. Phase I: SARS-CoV-2 PCR positivity [ Time Frame: 100 days after enrollment ]
    Duration of SARS-CoV-2 PCR positivity (in days) from nasooropharyngeal swabs until discharge or death

  6. Phase I: Detection of viable human SARS-CoV-2-specific T lymphocyte [ Time Frame: 100 days after enrollment ]
    Detection of viable human SARS-CoV-2-specific T lymphocyte after infusion

  7. Phase I: viral shedding in nasooropharyngeal swabs [ Time Frame: 100 days after enrollment ]
    Effect of viable human SARS-CoV-2-specific T lymphocyte infusion on viral shedding in nasooropharyngeal swabs


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04762186


Contacts
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Contact: Philipp Köhler, Dr. +49-221-478-85523 philipp.koehler@uk-koeln.de
Contact: Oliver A. Cornely, Prof. +49-221-478-85523 oliver.cornely@uk-koeln.de

Locations
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Germany
Department I for Internal Medicine University Hospital of Cologne Recruiting
Cologne, NRW, Germany, 50937
Contact: Philipp Köhler, Dr.    +49-221-478-85523    philipp.koehler@uk-koeln.de   
Contact: Oliver A. Cornely, Prof.    +49-221-478-85523    oliver.cornely@uk-koeln.de   
Principal Investigator: Philipp Köhler, Dr.         
Sub-Investigator: Oliver A. Cornely, Prof.         
Sponsors and Collaborators
Universitätsklinikum Köln
ZKS Köln
Hannover Medical School
Miltenyi Biomedicine GmbH
Investigators
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Principal Investigator: Philipp Köhler, Dr. Department I for Internal Medicine University Hospital of Cologne
More Information
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Responsible Party: Universitätsklinikum Köln
ClinicalTrials.gov Identifier: NCT04762186    
Other Study ID Numbers: Uni-Koeln-4480
First Posted: February 21, 2021    Key Record Dates
Last Update Posted: December 20, 2021
Last Verified: December 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Universitätsklinikum Köln:
COVID-19
T-Cell
SARS-CoV-2
 Infusion
Adoptive
Allogeneic
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
 Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases