T Cell Therapy for COVID-19

(TONI Trial)

Recruiting at 1 trial location

Overseen By Fahmida Hoq, MBBS

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's National Research Institute

Must not be taking: Monoclonal antibodies, JAK inhibitors

Disqualifiers: Active infections, Hypertension, Pulmonary disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 28

Duration: 45 days

24 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take certain medications like biological or immunosuppressive monoclonal antibodies targeting T cells, donor lymphocyte infusion, chimeric antigen receptor T cell infusion, or JAK inhibitors close to the CST infusion. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the T cell treatment for COVID-19?

Research shows that T cell therapy, which uses immune cells from recovered COVID-19 patients, has helped some immunocompromised patients recover from persistent COVID-19. Additionally, these T cells can recognize and attack different variants of the virus, suggesting they could be a promising treatment option. ^{1 2 3 4 5}

Is T cell therapy for COVID-19 safe for humans?

Research shows that SARS-CoV-2-specific T cell therapy is generally safe and well tolerated in humans, including those with severe COVID-19. Larger studies are needed to confirm these findings, but initial trials indicate that this therapy does not pose significant safety concerns. ^{1 2 4 6 7}

How is T Cell Therapy for COVID-19 different from other treatments?

T Cell Therapy for COVID-19 is unique because it uses virus-specific T cells from recovered patients to boost the immune response in those at risk of severe disease. Unlike standard treatments, this therapy involves transferring these specialized immune cells to help the body recognize and fight the virus more effectively, potentially offering a targeted approach against multiple variants of the virus. ^{1 2 3 4 6}

What is the purpose of this trial?

This is an open label, phase I dose-escalation study to evaluate the safety of coronavirus-specific T cell (CST) therapy for prevention of SARS-CoV-2 infection in immunocompromised patients following hematopoietic stem cell transplantation (HSCT). Participants will receive donor-derived CSTs for prevention of SARS-CoV-2 infection after HSCT (≥28 days and \<4 months after HSCT). In this dose escalation trial, three doses (1x107/m2, 2x107/m2, and 4x107/m2) will be tested for safety, with study arms for adult (≥18 years of age and \<80 years) HSCT recipients (Arm A) and pediatric (≥12 years of age and \<18 years) HSCT recipients (Arm B), and defined dose escalations in each study arm. The study agent will be assessed for safety (stopping rules defined) and antiviral activity.

Eligibility Criteria

This trial is for immunocompromised patients aged 12-80 who are post allogeneic hematopoietic stem cell transplantation (HSCT). They must be at risk of COVID-19, have stable vital signs, normal organ function tests, and not be pregnant or breastfeeding. Participants should not have active COVID-19 infection or recent vaccinations and must agree to use effective birth control.

Inclusion Criteria

Your white blood cell count is at least 500 cells per microliter.

I am a teen who had a stem cell transplant recently and am at risk for COVID-19.

Your oxygen levels have been consistently above 92% without needing extra oxygen for at least a week before starting the treatment.

Exclusion Criteria

Participants unwilling to utilize effective contraception during the study period (if applicable)

Your pulse pressure is more than 40 mmHg.

Donating cells would be harmful to my health or mental well-being.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive donor-derived coronavirus-specific T cells (CST) for prevention of SARS-CoV-2 infection after HSCT

45 days

Staggered infusions at least 28 days apart

Follow-up

Participants are monitored for safety and effectiveness after CST infusion

45 days

Regular monitoring visits

Long-term follow-up

Persistence of infused CSTs and antiviral activity are monitored

12 months

Treatment Details

Interventions

• Coronavirus-specific T cell (CST)

Trial Overview The study is testing the safety of donor-derived coronavirus-specific T cells (CST) in preventing COVID-19 after HSCT. It's an open-label phase I trial with dose escalation to determine safe levels for adults and children in separate arms based on their age.

Participant Groups

Group I: Prevention of SARS-CoV-2 infection in immunocompromised pediatric patients Experimental Treatment 1 Intervention

In this dose escalation trial, donor derive coronavirus-specific T cell (CST) (three doses, 1x107/m2, 2x107/m2, and 4x107/m2) will be tested for safety, with study arms for pediatric (≥12 years of age and \<18 years) HSCT recipients (Arm B).

Group II: Prevention of SARS-CoV-2 infection in immunocompromised adult patients Experimental Treatment 1 Intervention

In this dose escalation trial, donor derive coronavirus-specific T cell (CST) (three doses, 1x107/m2, 2x107/m2, and 4x107/m2) will be tested for safety, with study arms for adult (≥18 years of age and \<80 years) HSCT recipients (Arm A)

Coronavirus-specific T cell (CST) is already approved in United States for the following indications:

Approved in United States as ALVR109 for:

• Prevention of SARS-CoV-2 infection in immunocompromised patients following hematopoietic stem cell transplantation (HSCT)

Who Is Running the Clinical Trial?

Children's National Research Institute

Lead Sponsor

Trials

227

Recruited

258,000+

Findings from Research

In a study involving 6 immunocompromised patients with persistent COVID-19, the administration of SARS-CoV-2 viral-specific T cells (VSTs) showed partial responses in some patients, but the overall effectiveness and role of VSTs in recovery remain uncertain due to the use of other antiviral treatments.

Two patients fully recovered after receiving VSTs, but it was unclear if the VSTs were the primary factor in their recovery, highlighting the need for further research to understand the potential benefits of VSTs in treating persistent COVID-19 in immunocompromised individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy With Allogeneic Severe Acute Respiratory Syndrome Coronavirus-2-Specific T Cells for Persistent Coronavirus Disease 2019 in Immunocompromised Patients. Haidar, G., Jacobs, JL., Kramer, KH., et al.[2023]

A high percentage (93%) of convalescent COVID-19 donor blood samples met the criteria for generating SARS-CoV-2-specific cytotoxic T-cell lymphocytes (vCTLs), indicating a robust method for T-cell enrichment.

The manufactured SARS-CoV-2-vCTLs exhibited strong functionality, with 79% being IFN-γ+ T cells and a diverse T-cell receptor repertoire, suggesting their potential effectiveness in targeting and treating COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manufacture and Characterization of Good Manufacturing Practice-Compliant SARS-COV-2 Cytotoxic T Lymphocytes. Chu, Y., Milner, J., Lamb, M., et al.[2023]

Adoptive T-cell immunotherapy shows promise for treating viral infections, particularly in immunocompromised patients, by using HLA-matched T cells that can be rapidly expanded from healthy donors.

A study developed a SARS-CoV-2-specific T-cell bank from 12 convalescent individuals, demonstrating that these T cells can effectively target multiple SARS-CoV-2 antigens and remain functional against various virus variants, suggesting a potential treatment for active COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SARS-CoV-2-specific T cells generated for adoptive immunotherapy are capable of recognizing multiple SARS-CoV-2 variants. Panikkar, A., Lineburg, KE., Raju, J., et al.[2022]

SARS-CoV-2-specific T cells can be successfully manufactured from convalescent COVID-19 patients, showing strong cytotoxic potential and stability for up to 72 hours after collection, which is crucial for potential therapeutic use.

The study demonstrates that these T cells can specifically recognize and kill target cells, suggesting that adoptive transfer of these cells could enhance the immune response in COVID-19 patients at risk of severe disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Manufacturing of Highly Cytotoxic Clinical-Grade SARS-CoV-2-specific T Cell Products Covering SARS-CoV-2 and Its Variants for Adoptive T Cell Therapy. Bonifacius, A., Tischer-Zimmermann, S., Santamorena, MM., et al.[2022]

Adoptive cell therapy using SARS-CoV-2 specific T cells from recovered COVID-19 patients can be significantly enhanced by using specific cytokines, leading to over 1,000-fold expansion of these T cells while maintaining their functionality and ability to recognize viral antigens.

The study suggests a novel approach to improve the effectiveness of SARS-CoV-2 T cells by using CRISPR-Cas9 gene editing to inactivate the glucocorticoid receptor gene, which may help counteract the effects of corticosteroids used in severe COVID-19 cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of glucocorticoid-resistant SARS-CoV-2 T cells for adoptive cell therapy. Basar, R., Uprety, N., Ensley, E., et al.[2021]

The study identified SARS-CoV-2-specific T cells (SC2-STs) from 12 COVID-19 convalescent donors, which showed a strong effector memory phenotype and high levels of cytotoxicity markers, indicating their potential effectiveness in targeting COVID-19.

SC2-STs can be expanded and isolated in vitro, demonstrating their ability to respond specifically to viral antigens, making them a promising candidate for off-the-shelf T cell therapy to treat severe COVID-19 cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potency assessment of IFNγ-producing SARS-CoV-2-specific T cells from COVID-19 convalescent subjects. Gil-Bescós, R., Ostiz, A., Zalba, S., et al.[2023]

In a phase 1/2 trial involving 90 patients with severe COVID-19, treatment with convalescent donor-derived SARS-CoV-2-specific T cells (CoV-2-STs) combined with standard care resulted in a significantly higher recovery rate (65% vs. 38%) and a median recovery time of 11 days, indicating improved efficacy over standard care alone.

The CoV-2-ST treatment was found to be safe and well tolerated, with significant expansion of the T cells observed in patients receiving the treatment, suggesting a promising approach for immunotherapy in severe COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial. Papadopoulou, A., Karavalakis, G., Papadopoulou, E., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Therapy With Allogeneic Severe Acute Respiratory Syndrome Coronavirus-2-Specific T Cells for Persistent Coronavirus Disease 2019 in Immunocompromised Patients. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Manufacture and Characterization of Good Manufacturing Practice-Compliant SARS-COV-2 Cytotoxic T Lymphocytes. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

SARS-CoV-2-specific T cells generated for adoptive immunotherapy are capable of recognizing multiple SARS-CoV-2 variants. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Rapid Manufacturing of Highly Cytotoxic Clinical-Grade SARS-CoV-2-specific T Cell Products Covering SARS-CoV-2 and Its Variants for Adoptive T Cell Therapy. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Generation of glucocorticoid-resistant SARS-CoV-2 T cells for adoptive cell therapy. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Potency assessment of IFNγ-producing SARS-CoV-2-specific T cells from COVID-19 convalescent subjects. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial. [2023]