Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients

NCT05447013 | Unknown Phase 1

• 1 other identifier: CoV-2-STs-001
• Study Type: interventional
• Target: 182
• Locations: 1 country
• Sites: 2

Brief Summary

Open-label phase I (single-center)/ phase II (multicenter) with randomization 2:1

Conditions

Severe COVID-19

Keywords

COVID-19; Virus-specific T cells; SARS-CoV-2; Coronavirus-specific T cells; 2021-001022-22

Outcome Measures

Primary Outcomes (8)

• Establishment of a CoV-2-STs bank

  • Thirty, multi-dose, GMP-generated and released CoV-2-ST products

  Within 2 months before recruitment initiation

• Establishment of a CoV-2-STs bank of broad HLA coverage

  CoV-2-ST products of a broad HLA repertoire

  Within 2 months before recruitment initiation

• Pharmacodynamic endpoint-1 (Phase I)

  •Determination of optimal dose (maximum tolerated dose)

  Up to the completion of Ph I

• Pharmacodynamic endpoint-2 (Phase I and II)

  • In vivo expansion of CoV-2-STs after administration

  Up to the completion of Ph I and II

• Pharmacodynamic endpoint-3 (Phase II)

  • Persistence of circulating donor CoV-2-STs by microchimerism analysis

  Up to the completion of Ph II

• Efficacy endpoint-1 (Phase II)

  • Recovery and time to recovery. Recovery is defined as a value of 1 to 3 on the 8-point WHO ordinal scale (OS). Time to recovery is the days passed from Day 0 to the 1st day of a score 1 to 3 on the OS for those who recovered or the days passed from Day 0 to the last follow-up for the rest.

  Day 30 and Day 60 (end of follow up)

• Efficacy endpoint-2 (Phase II)

  • Survival by days 30 and 60. Survival is defined as the time-to-event from Day 0 to the date of death or the last follow-up

  Day 30 and Day 60 (end of follow up)

• Safety endpoints (Phase I and II)

  * acute toxicity related to the CoV-2-ST infusion, by clinical and laboratory assessments * cytokine release syndrome, by clinical and laboratory assessments * number of adverse and/or serious adverse events

  End-of-follow up (day 60) for all patients in Ph I and Ph II

Secondary Outcomes (4)

• Efficacy endpoint-1 (Phase II)

  Day 30 for all enrolled patients

• Efficacy endpoint-2 (Phase II)

  End-of-follow up (day 60)

• Efficacy endpoint-3 (Phase II)

  Day 20 for all enrolled patients

• Safety endpoint (Phase I and II)

  End-of-follow up (day 60)

Study Arms (2)

For Phase II: Arm A

EXPERIMENTAL

Standard of care (SOC) and Coronavirus-specific T cells (CoV-2-STs)

Biological: Coronavirus-2-specific T cells

For Phase II: Arm B

ACTIVE COMPARATOR

Standard of care (SOC)

Other: standard of care (SOC)

Interventions

Coronavirus-2-specific T cells BIOLOGICAL

Coronavirus-2-specific T cells ex vivo expanded from selected COVID-19 recovered donors

For Phase II: Arm A

standard of care (SOC) OTHER

standard of care (SOC)

For Phase II: Arm B

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pneumonia or/and SatO2 ≤94% on room air or/and respiratory rate ≥24breaths/min AND
• lymphopenia CD3+≤650/μl or/and ALC≤1000/microl AND
• Increased values of D-dimers (≥2Χ) or/and ferritin (\>1000ng/ml) or/and CRP (≥3Χ) or/and LDH (≥2Χ)

You may not qualify if:

• Age ≤18 and ≥80 years old
• Onset of symptoms \>8 days (immunosuppressed patients are excluded from the time limit when they become chronic carriers of the virus)
• Corticosteroid administration at a dose of \>0.75mg/kg (methylprednisolone equivalent)
• Multiple organ failure
• ARDS (acute respiratory distress syndrome)
• Mechanical ventilation
• Patients who received ATG, or Campath, or other T-cell-suppressing monoclonal antibody within 28 days prior to admission
• Patients with concomitant confirmed infection from another pathogen or with very high procalcitonin (PCT) that may indicate additional infection
• Enrollment in another clinical trial
• Pregnancy
• Inability to sign informed consent form
• Judged ineligible by at the treating physician (treating physician's discretion)
• Bilirubin ≥2x of upper normal limit
• AST ≥ 2x of upper normal limit
• Creatinine ≥ 2x of upper normal limit or with dialysis/hemodialysis needs

Sponsors & Collaborators

• George Papanicolaou Hospital: lead
• General Hospital Of Thessaloniki Ippokratio: collaborator

Study Sites (2)

General Hospital of Thessaloniki Ippokratio- 2nd Propedeutic Department of Internal Medicine

Thessaloniki, 54642, Greece

RECRUITING

George Papanikolaou Hospital - Gene and Cell Therapy Center- Hematology Dpt- Hematopoietic Stem Cell Transplant Center

Thessaloniki, 57010, Greece

RECRUITING

MeSH Terms

Conditions

COVID-19

Interventions

Standard of Care

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Evangelia Yannaki, MD,PI

  George Papanicolaou Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Evangelia Yannaki, MD, PI

CONTACT

+30 2313 307518; eyannaki@u.washington.edu

Michael Doumas, MD

CONTACT

+30 2310 992899; michalisdoumas@yahoo.co.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI, Director of the Gene and Cell Therapy Center, Hematology-HCT Unit

Study Record Dates

• First Submitted: June 30, 2022
• First Posted: July 7, 2022
• Study Start: June 2, 2021
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: November 23, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

GR (2)