Open-label phase I (single-center)/ phase II (multicenter) with randomization 2:1
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
Biological: Coronavirus-2-specific T cells
Coronavirus-2-specific T cells ex vivo expanded from selected COVID-19 recovered donors
Other: standard of care (SOC)
standard of care (SOC)
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
General Hospital of Thessaloniki Ippokratio- 2nd Propedeutic Department of Internal Medicine
Thessaloniki, Greece
George Papanikolaou Hospital - Gene and Cell Therapy Center- Hematology Dpt- Hematopoietic Stem Cell Transplant Center
Thessaloniki, Greece
Evangelia Yannaki, MD, PI
+30 2313 307518
eyannaki@u.washington.edu
Michael Doumas, MD
+30 2310 992899
michalisdoumas@yahoo.co.uk
Evangelia Yannaki, MD,PI, Principal Investigator
George Papanicolaou Hospital