Severe COVID-19Phase 1/2CoV-2-STsNCT05447013
Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients
A Phase 1/2 study testing Coronavirus-2-specific T cells in people with Severe COVID-19, run by George Papanicolaou Hospital at 2 sites in Greece.
Trial summary
Open-label phase I (single-center)/ phase II (multicenter) with randomization 2:1 Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Severe COVID-19
- What is being tested?
- Coronavirus-2-specific T cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 182 participants
- Where
- 2 sitesGreece
- Study dates
- 2 Jun 2021to 31 Dec 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
Show all 16Show fewer
- 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 locations and contacts
2 sites in 1 country.
Greece2 sites, 2 recruiting
- Recruiting
General Hospital of Thessaloniki Ippokratio- 2nd Propedeutic Department of Internal Medicine
Thessaloniki, 54642
Michael Doumas, MD, +30 2310 992899, michalisdoumas@yahoo.co.uk
- Recruiting
George Papanikolaou Hospital - Gene and Cell Therapy Center- Hematology Dpt- Hematopoietic Stem Cell Transplant Center
Thessaloniki, 57010
Evangelia Yannaki, MD, PI, +30 2313 307518, eyannaki@u.washington.edu
ANASTASIA PAPADOPOULOU, CO-PI, +30 2313 307963, apapadopoulou.gpapanikolaou@n3.syzefxis.gov.gr
About this study
Open-label phase I (single-center)/ phase II (multicenter) with randomization 2:1
Read the 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:
- 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
- Conditions
- Severe COVID-19
- Being tested
- Coronavirus-2-specific T cells, standard of care (SOC)
- Keywords
- COVID-19, Virus-specific T cells, SARS-CoV-2, Coronavirus-specific T cells, 2021-001022-22
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Coronavirus-2-specific T cellsBiological
Coronavirus-2-specific T cells ex vivo expanded from selected COVID-19 recovered donors
standard of care (SOC)Other
standard of care (SOC)
| Study group | Role | What they receive |
|---|---|---|
| For Phase II: Arm A | Experimental | Standard of care (SOC) and Coronavirus-specific T cells (CoV-2-STs) Receives: Biological: Coronavirus-2-specific T cells |
| For Phase II: Arm B | Active comparator | Standard of care (SOC) Receives: Other: standard of care (SOC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Establishment of a CoV-2-STs bank
- Thirty, multi-dose, GMP-generated and released CoV-2-ST products
Measured: 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
Measured: Within 2 months before recruitment initiation
Pharmacodynamic endpoint-1 (Phase I)
•Determination of optimal dose (maximum tolerated dose)
Measured: Up to the completion of Ph I
Pharmacodynamic endpoint-2 (Phase I and II)
- In vivo expansion of CoV-2-STs after administration
Measured: Up to the completion of Ph I and II
Pharmacodynamic endpoint-3 (Phase II)
- Persistence of circulating donor CoV-2-STs by microchimerism analysis
Measured: 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.
Measured: 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
Measured: 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
Measured: End-of-follow up (day 60) for all patients in Ph I and Ph II
Secondary outcomes (4)
Efficacy endpoint-1 (Phase II)
-Clinical status by the 8-point WHO Ordinal Scale on day 30
Measured: Day 30 for all enrolled patients
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)
Measured: End-of-follow up (day 60)
Efficacy endpoint-3 (Phase II)
Percentage of patients with negative PCR by day 20
Measured: Day 20 for all enrolled patients
Safety endpoint (Phase I and II)
•Graft versus host disease (GvHD), by clinical and laboratory assessments
Measured: End-of-follow up (day 60)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2022
- Study start2 Jun 2021
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 182 participants (estimated)
Sponsor and investigators
- Lead sponsor
- George Papanicolaou Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- General Hospital Of Thessaloniki Ippokratio
- Responsible party
- Principal investigator, Evangelia Yannaki, George Papanicolaou Hospital
- Investigators
- Evangelia Yannaki, MD,PI, Principal investigator, George Papanicolaou Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05447013
- Sponsor's protocol ID
- CoV-2-STs-001
- Acronym
- CoV-2-STs
- Status last verified
- Nov 2022
- First submitted
- 30 Jun 2022
- Last updated
- 23 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients
- ClinicalTrials.gov ID
- NCT05447013
- Acronym / sponsor ID
- CoV-2-STs / CoV-2-STs-001
- Conditions
- Severe COVID-19
- Keywords
- COVID-19, Virus-specific T cells, SARS-CoV-2, Coronavirus-specific T cells, 2021-001022-22
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 182 participants (estimated)
- Lead sponsor
- George Papanicolaou HospitalUniversity, hospital or other
- Collaborators
- General Hospital Of Thessaloniki Ippokratio
- Study start
- 2 Jun 2021 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 7 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| For Phase II: Arm A | Experimental | Biological: Coronavirus-2-specific T cellsStandard of care (SOC) and Coronavirus-specific T cells (CoV-2-STs) |
| For Phase II: Arm B | Active comparator | Other: standard of care (SOC)Standard of care (SOC) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (16 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Coronavirus-2-specific T cellsCoronavirus-2-specific T cells ex vivo expanded from selected COVID-19 recovered donors | Biological | For Phase II: Arm A |
| standard of care (SOC)standard of care (SOC) | Other | For Phase II: Arm B |
Primary outcome
Establishment of a CoV-2-STs bank
Time frame: Within 2 months before recruitment initiation
• Thirty, multi-dose, GMP-generated and released CoV-2-ST products
Establishment of a CoV-2-STs bank of broad HLA coverage
Time frame: Within 2 months before recruitment initiation
CoV-2-ST products of a broad HLA repertoire
Pharmacodynamic endpoint-1 (Phase I)
Time frame: Up to the completion of Ph I
•Determination of optimal dose (maximum tolerated dose)
Pharmacodynamic endpoint-2 (Phase I and II)
Time frame: Up to the completion of Ph I and II
• In vivo expansion of CoV-2-STs after administration
Pharmacodynamic endpoint-3 (Phase II)
Time frame: Up to the completion of Ph II
• Persistence of circulating donor CoV-2-STs by microchimerism analysis
Efficacy endpoint-1 (Phase II)
Time frame: Day 30 and Day 60 (end of follow up)
• 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.
Efficacy endpoint-2 (Phase II)
Time frame: Day 30 and Day 60 (end of follow up)
• 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
Safety endpoints (Phase I and II)
Time frame: End-of-follow up (day 60) for all patients in Ph I and Ph 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
4 secondary outcomes
Efficacy endpoint-1 (Phase II)
Time frame: Day 30 for all enrolled patients
Efficacy endpoint-2 (Phase II)
Time frame: End-of-follow up (day 60)
Efficacy endpoint-3 (Phase II)
Time frame: Day 20 for all enrolled patients
Safety endpoint (Phase I and II)
Time frame: End-of-follow up (day 60)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Evangelia Yannaki, MD,PI principal investigator
George Papanicolaou Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Coronavirus-2-specific T cells in people with Severe COVID-19, run by George Papanicolaou Hospital at 2 sites in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Evangelia Yannaki, MD, PI (+30 2313 307518, eyannaki@u.washington.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Establishment of a CoV-2-STs bank (time frame: Within 2 months before recruitment initiation). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2022.