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

• ClinicalTrials.gov Identifier: NCT04762186
• Recruitment Status: Not yet recruiting
• First Posted: February 21, 2021
• Last Update Posted: February 21, 2021
• Sponsor: Universitätsklinikum Köln
• Collaborators: ZKS Köln; MMH Institute for Transfusion Medicine; Miltenyi Biomedicine GmbH
• Information provided by (Responsible Party): Universitätsklinikum Köln

Study Description

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: IMP 1,000 plus SoC; Drug: IMP 5,000 plus SoC; Drug: IMP RP2D plus SoC; Drug: SoC	Phase 1; Phase 2

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 adoptive 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 adoptive SARS-CoV-2-specific T cells. This will be a randomized, prospective feasibility trial.

All study patients at WHO ordinal scale ≥ 5 will receive the current SoC for treatment of Covid-19. Currently this is remdesivir (loading dose 200mg i.v. on day 1, 100mg maintenance dose day two to five (up to day 10), dexamethasone 6mg once daily p.o. or i.v. up to day 10 and a subcutaneous thromboembolism prophylaxis with low molecular-weight heparin. Due to the dynamic of the ongoing COVID-19 pandemic, SoC treatments are underlying rapid changes and are continuously developed. Therefore, SoC treatment as defined at the time of respective IMP dosing, will be administered.

The adoptive SARS-CoV-2 specific T cells are suspended and formulated in 50 ml of platelet additive solution and will be administered intravenously within 15 min to 30 min.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment

Intervention Model 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 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 adoptive therapy with SARS-CoV-2-specific T cells. This will be a randomized, prospective feasibility trial.

• Masking: None (Open Label)

Masking Description

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

During phase II both study participants and the study team are aware of the treatment as this again is an open label trial.

• Primary Purpose: Treatment
• Official Title: A Randomized Phase I/II Trial to Analyse Safety and Efficacy of Adoptive SARS-CoV-2 Specific T Cell Transfer in Patients at Risk for Severe COVID-19
• Estimated Study Start Date: April 1, 2021
• Estimated Primary Completion Date: September 1, 2022
• Estimated Study Completion Date: December 1, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Phase I dose level 1; Dose level one consists of 3 study patients receiving 1,000 adoptive SARS-CoV-2 specific T cells (IMP) per kg BW. If the first recipient does not experience a DLT associated with the dose level one therapeutic cells within 28 days, the second and third patient will receive 1.000 SARS-CoV-2 adoptive SARS-CoV-2 specific T cells per kg BW. If patient second and third do not experience a DLT within 14 days after treatment, the dose level two will be initiated.	Drug: IMP 1,000 plus SoC; Intravenous administration of 1,000 adoptive SARS-CoV-2 specific T cells (IMP) per kg BW. The adoptive SARS-CoV-2 specific T cells are suspended and formulated in 50 ml of platelet additive solution and will be administered intravenously within 15 min to 30 min. All study patients at WHO Ordinal Scale ≥ 5 will receive the current SoC for treatment of COVID-19. Currently this is remdesivir (loading dose 200 mg i.v. on day 1, 100 mg maintenance dose day two to five (up to day 10)) - only WHO Ordinal Scale 5, dexamethasone 6 mg once daily p.o. or i.v. up to day 10 and a subcutaneous thromboembolism prophylaxis with low molecular-weight heparin.
Experimental: Phase I dose level 2; Dose level two consists of 3 study patients receiving 5.000 adoptive SARS-CoV-2 specific T cells (IMP) per kg BW. If the fourth patient does not experience a DLT associated with the dose level two within 28 days, the fifth and sixth patient will receive 5.000 adoptive SARS-CoV-2 specific T cells per kg BW.	Drug: IMP 5,000 plus SoC; Intravenous administration of 5,000 adoptive SARS-CoV-2 specific T cells (IMP) per kg BW. The adoptive SARS-CoV-2 specific T cells are suspended and formulated in 50 ml of platelet additive solution and will be administered intravenously within 15 min to 30 min. All study patients at WHO Ordinal Scale ≥ 5 will receive the current SoC for treatment of COVID-19. Currently this is remdesivir (loading dose 200 mg i.v. on day 1, 100 mg maintenance dose day two to five (up to day 10)) - only WHO Ordinal Scale 5, dexamethasone 6 mg once daily p.o. or i.v. up to day 10 and a subcutaneous thromboembolism prophylaxis with low molecular-weight heparin.
Experimental: Phase II SoC plus IMP at the RP2D; Phase II SoC plus IMP at the RP2D consists of 26 patients treated with SoC plus adoptive SARS-CoV-2-specific T cells at the RP2D (Recommended Phase II Dose).	Drug: IMP RP2D plus SoC; Intravenous administration adoptive SARS-CoV-2 specific T cells (IMP) at Recommended Phase II Dose (RP2D). The adoptive SARS-CoV-2 specific T cells are suspended and formulated in 50 ml of platelet additive solution and will be administered intravenously within 15 min to 30 min.
Active Comparator: Phase II SoC; Phase II SoC consists of 13 patients treated with SoC.	Drug: SoC; Patients will receive the current SoC for treatment of COVID-19. Currently this is remdesivir (loading dose 200 mg i.v. on day 1, 100 mg maintenance dose day two to five (up to day 10)) - only WHO Ordinal Scale 5, dexamethasone 6 mg once daily p.o. or i.v. up to day 10 and a subcutaneous thromboembolism prophylaxis with low molecular-weight heparin.

Outcome Measures

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
2. Phase II: [ Time Frame: 28 days ]
   AUC of the course defined by the WHO ordinal scale for COVID-19

Secondary Outcome Measures :

1. Safety outcome measures [ Time Frame: 3 Month ]
   The rate and severity of adverse events after infusion of SARS-CoV-2 specific T cells during the trial
2. Acute graft- vs. -host disease [ Time Frame: 100 days after randomization ]
   Clinical manifestations of acute graft- vs. -host disease at day 100 after randomization

Eligibility Criteria

• 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
• 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 for example 6mg dexamethasone per os or intravenous 1x/d (SoC) and steroids at a prednisolone equivalent of <1 mg/kg BW) are allowed
  • Autologous transplant during the past 3 months
  • Allogeneic transplant during the past year or ongoing immunosuppression or chronic Graft-versus-Host Disease

Exclusion criteria:

• Participation in any other clinical trial of an experimental agent treatment for COVID-19
• COVID-19 WHO ordinal scale ≥6
• Anticipated life-expectancy <72 hours
• Expected duration of hospital stay <72 hours
• Leukocytes <1000/µl or platelets <50.000/µl unless resulting from underlying disease or it's treatment
• CT pneumonia score ≥13 [50]
• Any other Steroids ≥ 1mg/kg Prednisolone-equivalent/kg BW, besides 6mg Dexamethasone i.v. or p.o. 1x/d (Standard of Care)
• 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

• 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

[not yet final]

Contacts and Locations

Contacts

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

Germany

Department I for Internal Medicine University Hospital of Cologne

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

MMH Institute for Transfusion Medicine

Miltenyi Biomedicine GmbH

Investigators

• Principal Investigator: Philipp Köhler, Dr.; Department I for Internal Medicine University Hospital of Cologne

More Information

• Responsible Party: Universitätsklinikum Köln
• ClinicalTrials.gov Identifier: NCT04762186
• Other Study ID Numbers: Uni-Koeln-4480
• First Posted: February 21, 2021
• Last Update Posted: February 21, 2021
• Last Verified: February 2021

• 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