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

NCT04762186 | Terminated Phase 1 DMC

• 1 other identifier: Uni-Koeln-4480
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Moderate COVID-19-infection

Keywords

COVID-19; T-Cell; SARS-CoV-2; Infusion; Adoptive; Allogeneic

Outcome Measures

Primary Outcomes (1)

• Phase I: Dose-limiting toxicities

  Dose-limiting toxicities until Day 28 after infusion of SARS-CoV-2- specific T cells

  28 days

Secondary Outcomes (7)

• Phase I: Safety

  3 Month

• Phase I: Acute graft- vs. -host disease

  100 days after enrollment

• Phase I: Clinical status

  100 days after enrollment

• Phase I: Hospitalization

  100 days after enrollment

• Phase I: SARS-CoV-2 PCR positivity

  100 days after enrollment

Study Arms (1)

Dose escalation

EXPERIMENTAL

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

Drug: human SARS-CoV 2 specific T lymphocytes

Interventions

human SARS-CoV 2 specific T lymphocytes 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.

Dose escalation

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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:

Sponsors & Collaborators

• Universitätsklinikum Köln: lead
• ZKS Köln: collaborator
• Hannover Medical School: collaborator
• Miltenyi Biomedicine GmbH: collaborator

Study Sites (1)

Department I for Internal Medicine University Hospital of Cologne

Cologne, North Rhine-Westphalia, 50937, Germany

Location

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Philipp Köhler, Dr.

  Department I for Internal Medicine University Hospital of Cologne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: During the dose-escalation phase, the study participants and the study team are aware of the treatment as this is an open label trial.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This trial consist of an open-label dose escalation phase in SARS-CoV-2 infected participants.

Study Record Dates

• First Submitted: February 11, 2021
• First Posted: February 21, 2021
• Study Start: December 8, 2021
• Primary Completion: August 3, 2022
• Study Completion: August 3, 2022
• Last Updated: September 15, 2022

Record last verified: 2022-09

Locations

DE (1)