Clinical trial NCT05447013: Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients
Official title: Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Severe COVID-19
Keywords: COVID-19
Virus-specific T cells
SARS-CoV-2
Coronavirus-specific T cells
2021-001022-22
Lead sponsor: George Papanicolaou Hospital
Sponsor class: OTHER
Collaborators: name: General Hospital Of Thessaloniki Ippokratio
First posted: 2022-07-07
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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

Eligibility 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

Primary outcomes:
measure: Establishment of a CoV-2-STs bank
timeFrame: Within 2 months before recruitment initiation
measure: Establishment of a CoV-2-STs bank of broad HLA coverage
timeFrame: Within 2 months before recruitment initiation
measure: Pharmacodynamic endpoint-1 (Phase I)
timeFrame: Up to the completion of Ph I
measure: Pharmacodynamic endpoint-2 (Phase I and II)
timeFrame: Up to the completion of Ph I and II
measure: Pharmacodynamic endpoint-3 (Phase II)
timeFrame: Up to the completion of Ph II
measure: Efficacy endpoint-1 (Phase II)
timeFrame: Day 30 and Day 60 (end of follow up)
measure: Efficacy endpoint-2 (Phase II)
timeFrame: Day 30 and Day 60 (end of follow up)
measure: Safety endpoints (Phase I and II)
timeFrame: End-of-follow up (day 60) for all patients in Ph I and Ph II
Secondary outcomes:
measure: Efficacy endpoint-1 (Phase II)
timeFrame: Day 30 for all enrolled patients
measure: Efficacy endpoint-2 (Phase II)
timeFrame: End-of-follow up (day 60)
measure: Efficacy endpoint-3 (Phase II)
timeFrame: Day 20 for all enrolled patients
measure: Safety endpoint (Phase I and II)
timeFrame: End-of-follow up (day 60)
Other outcomes:
Locations:
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki Ippokratio- 2nd Propedeutic Department of Internal Medicine
city: Thessaloniki
country: Greece
facility: George Papanikolaou Hospital - Gene and Cell Therapy Center- Hematology Dpt- Hematopoietic Stem Cell Transplant Center
Study officials:
affiliation: George Papanicolaou Hospital
name: Evangelia Yannaki, MD,PI
role: PRINCIPAL_INVESTIGATOR
References: