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

General Hospital of Thessaloniki "George Papanikolaou"

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Severe COVID-19

Treatments: Biological: Coronavirus-2-specific T cells; Other: standard of care (SOC)

Study type: Interventional

Funder types: Other

Identifiers

NCT05447013

CoV-2-STs-001

Details and patient eligibility

About

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

Full description

Phase I (single-center): The investigators will administer CoV-2-STs in a dose escalation regimen of 2 dose levels (DL1: 1,5x10^7 CoV-2-STs in total; DL2: 2x10^7 CoV-2-STs/m^2). 3 patients will be treated at each dose level (traditional 3+3 design) following by a 12-day wait period to assess safety of the infusions prior to escalating the next dose level (maximum 12 patients). The maximum tolerated dose will be determined Phase II (multicenter): Randomization 2:1, 60 patients will receive the standard of care (SOC) plus CoV-2-STs (ARM A) at the optimum dose which will be determined in phase I and 30 patients will receive only SOC (Arm Β) Phase II (multicenter, extension): Randomization 2:1, 53 patients will be enrolled in Arm A to receive SOC and up to two doses of COV-2-STs and 27 patients will receive only SOC.

Randomization: Patients who meet the eligibility criteria after signing the informed consent form they will randomly be assigned at 2:1 ratio to each of the 2 treatment groups. Patients assigned to arm A will be HLA-typed for HLA-A, B and DRB1 within 24h, and a suitable for them T cell product will be selected from the cell bank. If a suitable product is found, they will continue to arm A, otherwise, they will be assigned to arm B.

Objectives:

i) To determine the feasibility of establishing a bank with GMP-compliant generated SARS-CoV-2 specific T-cells (CoV-2-STs), well-characterized in terms of specificity, phenotype and expression of human leucocyte antigens (HLA), which will be produced by 30 COVID-19 recovered donors with broad HLA diversity in order to be suitable for administration to at least 90 COVID-19 patients ii) To determine the safety of CoV-2-ST administration as cellular immunotherapy in COVID-19 patients, who meet specific inclusion criteria iii) To determine the efficacy of CoV-2-ST administration as cellular immunotherapy in COVID-19 patients, who meet specific inclusion criteria

Enrollment: 182 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: Hospitalized patients, SARS-CoV-2 PCR positive, within 8 days from the onset of the symptoms (immunosuppressed patients are excluded from the time limit when they become chronic carriers of the virus), who have:

• 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)

Exclusion Criteria:

• 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
• Karnofsky score ≤50

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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182 participants in 2 patient groups

For Phase II: Arm A

Experimental group

Description:

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

Treatment:

Biological: Coronavirus-2-specific T cells

For Phase II: Arm B

Active Comparator group

Description:

Standard of care (SOC)

Treatment:

Other: standard of care (SOC)