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

NCT ID: NCT04762186

Last Updated: 2022-09-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-08
• Study Completion Date: 2022-08-03

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.

Conditions

Moderate COVID-19-infection

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose escalation

SARS CoV-2 infected participants will receive a single infusion over 15 to 30 minutes

Group Type: EXPERIMENTAL

human SARS-CoV 2 specific T lymphocytes

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ZKS Köln

OTHER

Sponsor Role: collaborator

Hannover Medical School

OTHER

Sponsor Role: collaborator

Miltenyi Biomedicine GmbH

INDUSTRY

Sponsor Role: collaborator

Universitätsklinikum Köln

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philipp Köhler, Dr.

Role: PRINCIPAL_INVESTIGATOR

Department I for Internal Medicine University Hospital of Cologne

Locations

Department I for Internal Medicine University Hospital of Cologne

Cologne, North Rhine-Westphalia, Germany

Countries

Germany

Other Identifiers

Uni-Koeln-4480

Identifier Type: -

Identifier Source: org_study_id