Thymalfasin for Coronavirus Vaccine Response

Overseen By Eleftherios Mylonakis, MD, PhD

Age: 65+

Sex: Any

Trial Phase: Phase 1

Sponsor: The Methodist Hospital Research Institute

Must not be taking: High-dose corticosteroids, Immunosuppressants

Disqualifiers: Hypoxemia, Advanced cancer, Immunocompromised, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 week

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Thymalfasin (Ta1) can enhance the immune response to the COVID-19 vaccine. Researchers aim to determine if different doses of Ta1 taken before vaccination can strengthen the body's defense system. The trial will also assess the safety of Ta1 and any potential side effects. It is suitable for individuals aged 65 and older preparing for a COVID-19 vaccine booster, provided they do not have serious health conditions like advanced cancer or severe immunodeficiency. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on certain treatments like high-dose corticosteroids or other immunosuppressive drugs, you may be excluded from participating.

Is there any evidence suggesting that Thymalfasin (Ta1) is likely to be safe for humans?

Research has shown that Thymalfasin, also known as Thymosin Alpha 1 or Ta1, is safe in various situations. It strengthens the immune system in older adults and those with weakened immune systems. Previous studies found that Ta1 improved the body's response to the flu vaccine and reduced flu infections, particularly in older individuals. Additionally, Ta1 has been safely administered to patients using dosing schedules similar to those planned for this trial. Although information on the optimal dose is limited, available research suggests that Ta1 is generally well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the typical coronavirus vaccines that rely on stimulating the immune system directly, Thymalfasin, also known as Thymosin Alpha 1 (Ta1), works by boosting the immune system's overall response capacity. This peptide enhances T-cell activity, which is crucial for a robust defense against viruses. Researchers are excited about Ta1 because it offers a complementary approach, potentially increasing the effectiveness of vaccines by priming the immune system before vaccination. Additionally, Ta1's ability to be administered quickly over a short period makes it a promising candidate for rapid immune enhancement.

What evidence suggests that Thymalfasin might be an effective treatment for increasing the immune response to the COVID-19 vaccine?

Research has shown that Thymalfasin, also known as Ta1, may enhance the immune system's response to vaccines. Studies have found that Ta1 can improve vaccine efficacy, particularly in older adults and individuals with weakened immune systems due to kidney disease. In this trial, participants in Treatment Arm A will receive a 4.8 mg dose of Ta1 on Day 0, followed by vaccination, while those in Treatment Arm B will receive the same dose on Day 0 and Day 3, followed by vaccination. However, debate continues regarding its effectiveness in treating COVID-19 itself. Despite this uncertainty, Ta1 is frequently used in treating COVID-19 patients. These findings suggest that Ta1 might help the body respond better to COVID-19 vaccines. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 65 or older who are scheduled to receive a COVID-19 vaccine booster and can consent to the study. They must agree to use barrier contraception post-treatment. People with severe immune compromise, certain medical conditions like advanced cancer, kidney failure, liver disease, heart failure, or those recently treated with investigational drugs cannot participate.

Inclusion Criteria

I am 65 years old or older.

Subjects must be able and willing to provide informed consent or have consent provided by a legally authorized representative (LAR)

I am scheduled to receive a COVID-19 mRNA booster shot.

Exclusion Criteria

My immune system is significantly weakened.

I have a history of anemia or bleeding disorders.

My kidney function has recently worsened significantly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 4.8 mg dose of Ta1 on Day 0 and Day 3 (Treatment arm B) or only on Day 0 (Treatment arm A), followed by COVID-19 vaccination

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including the incidence of treatment-emergent adverse events

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Thymalfasin (Thymosin Alpha 1; Ta1)

Trial Overview The study tests Thymalfasin (Ta1), which may boost the immune response to COVID-19 vaccines in older adults. Participants will receive different doses of Ta1 before their vaccine booster to assess its safety and effectiveness at enhancing vaccine-induced immunity.

How Is the Trial Designed?

Group I: Treatment arm B Experimental Treatment 1 Intervention

A 4.8 mg dose of Ta1 (dose of 1.6 mg in 1 mL of diluent X3) on Day 0 and Day 3, followed by vaccination

Group II: Treatment arm A Experimental Treatment 1 Intervention

A 4.8 mg dose of Ta1 (dose of 1.6 mg in 1 mL of diluent X3) on Day 0, followed by vaccination

Group III: Control Active Control 1 Intervention

No Ta1 prior to vaccination

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Published Research Related to This Trial

In a study of 49 hospitalized COVID-19 patients with low-flow and high-flow oxygen needs, thymosin-α-1 (Tα1) treatment showed a trend towards improved clinical recovery compared to standard care, although the differences were not statistically significant.

Tα1 treatment significantly increased CD4+ T cell counts in patients requiring low-flow oxygen by day 5, indicating a potential mechanism for its efficacy in enhancing immune response in COVID-19 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Trial of Thymalfasin (Thymosin-α-1) to Treat Hospitalized Patients With Hypoxemia and Lymphocytopenia Due to Coronavirus Disease 2019 Infection. Shehadeh, F., Benitez, G., Mylona, EK., et al.[2023]

Thymosin alpha 1 treatment in COVID-19 patients was associated with a significant reduction in 28-day mortality, with a hazard ratio of 0.45, indicating it may improve survival outcomes compared to standard care.

Patients receiving thymosin alpha 1 showed a greater decrease in C-reactive protein levels, a marker of inflammation, suggesting that it may help reduce inflammation in COVID-19, although it did not significantly affect ventilator-free days or lymphocyte counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Thymosin alpha 1 for the adjuvant treatment of coronavirus disease 2019: a retrospective cohort study]. Wang, T., Lin, Q., Xie, Y., et al.[2022]

In a phase II trial involving 25 patients with unresectable hepatocellular carcinoma (HCC), the combination of transarterial chemoembolization (TACE) and thymalfasin showed a higher rate of patients becoming eligible for transplant (28.6%) compared to TACE alone (0%).

Patients receiving TACE plus thymalfasin had a median overall survival of 110.3 weeks, compared to 57.0 weeks for those receiving TACE alone, and experienced fewer bacterial infections, suggesting a potential benefit of thymalfasin in enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of thymalfasin plus transarterial chemoembolization for unresectable hepatocellular carcinoma. Gish, RG., Gordon, SC., Nelson, D., et al.[2023]

Thymalfasin (thymosin-alpha 1) is an immunomodulating agent that enhances the Th1 immune response and has shown potential in treating various diseases, including chronic hepatitis B and C, AIDS, and certain cancers.

It works by improving immune system parameters, promoting T-cell differentiation and maturation, and has demonstrated efficacy in experimental models of immune dysfunction, particularly in infectious diseases and cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thymalfasin: an immune system enhancer for the treatment of liver disease. Sjogren, MH.[2018]

Thymalfasin (thymosin-alpha 1) is an immunomodulating agent that enhances the Th1 immune response and has shown potential in treating various diseases, including chronic hepatitis B and C, AIDS, and cancer, by improving immune system function.

In experimental models, thymalfasin has demonstrated efficacy in reconstituting immune function and exerting antitumor effects, particularly in cases of infectious diseases and cancers like melanoma and colorectal carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thymalfasin: an immune system enhancer for the treatment of liver disease. Sjogren, MH.[2018]

Thymalfasin (thymosin-alpha1) enhances specific T lymphocyte functions, particularly boosting T helper 1 cell responses that are crucial for fighting viral infections.

It shows promising potential as a standalone treatment for chronic hepatitis B and in combination with interferon-alpha for both chronic hepatitis B and C, warranting further large-scale clinical trials to optimize its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thymalfasin: clinical pharmacology and antiviral applications. Gramenzi, A., Cursaro, C., Andreone, P., et al.[2018]

In a phase III clinical study involving 105 moderate-to-severe COVID-19 patients, Thymosin α1 (Tα1) significantly reduced the death rate to 11.1% compared to 38.5% in the placebo group, indicating its potential efficacy in improving survival rates.

Tα1 also contributed to shorter hospital stays and reduced oxygen support needs, suggesting it positively impacts recovery time and overall patient outcomes when used alongside standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Double-blind Multicenter Two-arm Randomized Placebo-controlled Phase-III Clinical Study to Evaluate the Effectiveness and Safety of Thymosin α1 as an Add-on Treatment to Existing Standard of Care Treatment in Moderate-to-severe COVID-19 Patients. Shetty, A., Chandrakant, NS., Darnule, RA., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04487444

Thymalfasin (Thymosin Alpha 1) to Treat COVID-19 Infection Ta1 has also demonstrated improvement in response to vaccines in the elderly and in patients immunocompromised by renal disease.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9977612/

A pilot trial of Thymalfasin (Ta1) to prevent covid-19 infection ... Ta1 has also demonstrated improvement in response to vaccines in the elderly and in patients immunocompromised by renal disease [14], [15], [16] ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1567576922010694

Thymosin alpha1 use in adult COVID-19 patients Thymosin alpha1 (Ta1) is widely used to treat patients with coronavirus disease 2019 (COVID-19), however, its effect remains unclear.

4. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.673693/full

Efficacy of Thymosin Alpha 1 in the Treatment of COVID-19 Conclusion: Tα1 use in COVID-19 patients was associated with an increased non-recovery rate, especially in those with greater disease severity. Introduction.

5. fda.gov fda.gov/media/183892/download

Thymosin alpha-1 (Ta1) related bulk drug substances • There are insufficient data to establish effectiveness of Ta1 for use in ... Effectiveness – Depressed Response to Vaccinations;. Adjuvant to “ ...

6. trialx.com trialx.com/clinical-trials/listings/322584/thymalfasin-thymosin-alpha-1-ta1-as-an-enhancer-of-vaccine-response-among-older-adults-receiving-booster-doses-of-covid-19-vaccine/

Thymalfasin (Thymosin Alpha 1; Ta1) ... This research study will test the safety and possible harms of Ta1 when it is given to people at different dose levels before COVID-19 ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1567576923002709

A pilot trial of Thymalfasin (Ta1) to prevent covid-19 ... Ta1 has been shown to be safely administered to HD patients on a similar schedule to the one used in the current trial, and was efficacious in enhancing ( ...