T Cell Therapy for COVID-19

(TONI Trial)

Recruiting at 2 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new coronavirus-specific T cell therapy, focusing on preventing COVID-19 in individuals with weakened immune systems who recently received a stem cell transplant. Researchers will test three different doses to determine which is safest and most effective. Participants should have undergone a stem cell transplant between 28 days and four months ago and be at risk of contracting COVID-19. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that coronavirus-specific T cell (CST) therapy has been tested in several studies to assess its safety. In one study, researchers administered CSTs to 12 patients with weakened immune systems, and the results were promising, with no serious side effects. Another study using similar virus-specific T cells also found the treatment well-tolerated.

These findings suggest that CST therapy might be safe for humans, particularly those with weak immune systems. However, since this trial is in an early stage, it primarily aims to understand the safety of different dose levels. While the initial results are encouraging, the complete safety profile is still being determined. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard COVID-19 treatments, which often include antiviral drugs and monoclonal antibodies, Coronavirus-specific T cell (CST) therapy offers a unique approach by using the body's own immune system to fight the virus. CST therapy harnesses specially trained T cells that specifically target and destroy cells infected with the coronavirus. Researchers are excited about this treatment because it has the potential to provide long-lasting immunity and may be effective even against different variants of the virus, which is a limitation with current treatments. This targeted immune response could lead to quicker recovery times and offer protection where other treatments may fall short.

What evidence suggests that this trial's treatments could be effective for preventing SARS-CoV-2 infection in immunocompromised patients?

Research shows that coronavirus-specific T cell (CST) therapy could aid in treating COVID-19. In earlier studies, patients with severe COVID-19 who received CST therapy found it safe and practical. For patients with weakened immune systems, especially those at high risk of severe COVID-19, CSTs have successfully strengthened the immune response. These special T cells are designed to find and attack the virus directly, boosting the body's natural defenses. While research continues, early results suggest this method could effectively prevent or treat COVID-19 in more vulnerable individuals. Participants in this trial will receive CST therapy, with different arms for adults, older children, and young children to evaluate its effectiveness across age groups. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Young children (2 to <12 years) Experimental Treatment 1 Intervention

Arm C will include pediatric participants who are at least 2 years of age but younger than 12 years.

Group II: Older children (12 to <18 years) Experimental Treatment 1 Intervention

Arm B will include adolescent participants who are at least 12 years of age but younger than 18 years.

Group III: Adults (18 to <80 years) Experimental Treatment 1 Intervention

Arm A will include adult participants who are at least 18 years of age but younger than 80 years.

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

Citations

1. academic.oup.com academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaf302/8159933

Effectiveness and Safety of Autologous Virus-Specific T-Cell ... In this prospective study (N = 12), autologous virus-specific T cells (auto-VSTs) were successfully manufactured in 10 patients (83.3%).

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37460756/

SARS-CoV-2-specific T cell therapy for severe COVID-19 Overall, in hospitalized patients with severe COVID-19, adoptive immunotherapy with CoV-2-STs was feasible and safe.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05141058?cond=COVID-19

T Cell Therapy Opposing Novel COVID-19 Infection in ... 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 ...

4. mdpi.com mdpi.com/1422-0067/25/19/10512

SARS-CoV-2-Specific T-Cell as a Potent Therapeutic ... This study explored the potential of adoptive immunotherapy and harnessing the protective abilities using virus-specific T cells (VSTs).

5. sciencedirect.com sciencedirect.com/science/article/pii/S1465324924007205

A phase I/II study of adoptive SARS-CoV-2-specific T cells ... We report herein the safety and outcomes of 12 immunocompromised patients with or at risk of severe COVID-19 after infusion of adoptive SARS-COV-2-specific T ...