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

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

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

Study Overview

• Status: Terminated
• Conditions: Moderate COVID-19-infection
• Intervention / Treatment: Drug: human SARS-CoV 2 specific T lymphocytes

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 Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • NRW
    • Cologne, NRW, Germany, 50937
      • Department I for Internal Medicine University Hospital of Cologne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Dose-limiting toxicities	Dose-limiting toxicities until Day 28 after infusion of SARS-CoV-2- specific T cells	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Safety	The rate and severity of adverse events after infusion of SARS-CoV-2 specific T cells during the trial	3 Month
Phase I: Acute graft- vs. -host disease	Clinical manifestations of acute graft- vs. -host disease at day 100 after randomization	100 days after enrollment
Phase I: Clinical status	Clinical status as assessed on the WHO ordinal scale	100 days after enrollment
Phase I: Hospitalization	duration in days	100 days after enrollment
Phase I: SARS-CoV-2 PCR positivity	Duration of SARS-CoV-2 PCR positivity (in days) from nasooropharyngeal swabs until discharge or death	100 days after enrollment
Phase I: Detection of viable human SARS-CoV-2-specific T lymphocyte	Detection of viable human SARS-CoV-2-specific T lymphocyte after infusion	100 days after enrollment
Phase I: viral shedding in nasooropharyngeal swabs	Effect of viable human SARS-CoV-2-specific T lymphocyte infusion on viral shedding in nasooropharyngeal swabs	100 days after enrollment

Collaborators and Investigators

• Sponsor: Universitätsklinikum Köln
• Collaborators: Hannover Medical School; Miltenyi Biomedicine GmbH; ZKS Köln
• Investigators: Principal Investigator: Philipp Köhler, Dr., Department I for Internal Medicine University Hospital of Cologne

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 8, 2021
• Primary Completion (ACTUAL): August 3, 2022
• Study Completion (ACTUAL): August 3, 2022

Study Registration Dates

• First Submitted: February 11, 2021
• First Submitted That Met QC Criteria: February 18, 2021
• First Posted (ACTUAL): February 21, 2021

Study Record Updates

• Last Update Posted (ACTUAL): September 15, 2022
• Last Update Submitted That Met QC Criteria: September 12, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; T-Cell; Allogeneic; Infusion; Adoptive
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: Uni-Koeln-4480

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No