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

Severe COVID-19 Clinical Trial

— CoV-2-STs  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05447013
• Other study ID #: CoV-2-STs-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 2, 2021
• Est. completion date: December 31, 2022

Study information

• Verified date: November 2022
• Source: George Papanicolaou Hospital
• Contact: Evangelia Yannaki, MD, PI
• Phone: +30 2313 307518
• Email: eyannaki[@]u.washington.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 182
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 (=2?) or/and ferritin (>1000ng/ml) or/and CRP (=3?) or/and LDH (=2?)

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

Related Conditions & MeSH terms

• COVID-19
• Severe COVID-19

Intervention

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)

Locations

Country	Name	City	State
Greece	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

Sponsors (2)

Lead Sponsor	Collaborator
George Papanicolaou Hospital	General Hospital Of Thessaloniki Ippokratio

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Establishment of a CoV-2-STs bank	• Thirty, multi-dose, GMP-generated and released CoV-2-ST products	Within 2 months before recruitment initiation
Primary	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
Primary	Pharmacodynamic endpoint-1 (Phase I)	•Determination of optimal dose (maximum tolerated dose)	Up to the completion of Ph I
Primary	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
Primary	Pharmacodynamic endpoint-3 (Phase II)	• Persistence of circulating donor CoV-2-STs by microchimerism analysis	Up to the completion of Ph II
Primary	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)
Primary	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)
Primary	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	Efficacy endpoint-1 (Phase II)	-Clinical status by the 8-point WHO Ordinal Scale on day 30	Day 30 for all enrolled patients
Secondary	Efficacy endpoint-2 (Phase II)	time to improvement by 1 & 2 categories from day 0 according to the 8-point Ordinal Scale; time to PCR negativity; time to lymphopenia recovery; hospitalization time ( day 0 to discharge)	End-of-follow up (day 60)
Secondary	Efficacy endpoint-3 (Phase II)	Percentage of patients with negative PCR by day 20	Day 20 for all enrolled patients
Secondary	Safety endpoint (Phase I and II)	•Graft versus host disease (GvHD), by clinical and laboratory assessments	End-of-follow up (day 60)