Thymalfasin (Thymosin Alpha 1; Ta1) as an Enhancer of Vaccine Response Among Older Adults Receiving Booster Doses of COVID-19 Vaccine

Inclusion criteria

Subjects who meet all of the following criteria will be eligible to participate in the study:

• Age 65 or greater.
• Able and willing to provide informed consent or have consent provided by a legally authorized representative (LAR).
• Scheduled for SARS-CoV-2 mRNA vaccination booster dose.
• If a male subject, the subject must agree to use barrier contraception (ie, condoms) from Day 1 through 30 days following the last dose of study drug.

Exclusion criteria

Subjects who meet any of the following criteria will be excluded from participation in the study.

Laboratory related exclusion criteria should be assessed using historical records and lab results available in the subjects' electronic medical records.

• Hypoxemia for any reason, defined as either oxygen saturation (SpO2) ≤ 93% on room air or a requirement for supplemental oxygen support.
• Participants with one of the following:

• Acute liver failure defined as INR ≥ 1.5 and altered mental status in a patient without cirrhosis or pre-existing liver disease.
• Acute kidney failure defined as an increase in serum creatinine of ≥0.3 mg/dL within 48 hours or ≥50% within 7 days OR urine output of <0.5 mL/kg/hour for >6 hours
• Heart failure with NYHA functional classification III or IV.
• Advanced cancer being treated with cytotoxic chemotherapy.
• Participants have end stage renal disease requiring hemodialysis or peritoneal dialysis, or chronic kidney disease with GFR < 30 mL/min/1.73m2
• Participants with a known history of cirrhosis and Child-Pugh score B or C.
• Participants who are moderately or severely immunocompromised defined as:

• Are receiving active treatment for solid tumor and hematologic malignancies.
• Have hematologic malignancies (e.g., chronic lymphocytic lymphoma, non Hodgkin lymphoma, multiple myeloma, acute leukemia) and are known to have poor responses to COVID-19 vaccines, regardless of the treatment status for the hematologic malignancy.
• Received a solid-organ or islet transplant and are receiving immunosuppressive therapy.
• Received chimeric antigen receptor T cell (CAR T-cell) therapy or a hematopoietic cell transplant (HCT) and are within 2 years of transplantation or are receiving immunosuppressive therapy.
• Have a moderate or severe primary immunodeficiency (e.g., severe combined immunodeficiency, DiGeorge syndrome, Wiskott-Aldrich syndrome, common variable immunodeficiency disease).
• Have advanced or untreated HIV infection (defined as people with HIV and CD4 T lymphocyte cell counts <200 cells/mm3, a history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV).
• Are receiving active treatment with high-dose corticosteroids (i.e., ≥20 mg prednisone or equivalent per day for ≥2 weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, or immunosuppressive or immunomodulatory biologic agents (e.g., B cell-depleting agents).
• Participants with uncontrolled autoimmune or rheumatologic disease.
• Participants have received 6 doses or more of the COVID-19 vaccine. (Removed in Amendment 3)
• Participants with a history of myocarditis, pericarditis, or myopericarditis.
• Participants with a history of anemia or bleeding disorders. For anemia, the exclusion criterion will be met if any of the following are true:

i. Active anemia, defined as Hb<9 g/dL within 30 days prior to screening, ii. Unresolved anemia: Hb<11 g/dL (females) or <12 g/dL (males) during any window of >=3 months in the past year AND no evidence of measures of correction (e.g. iron supplementation, transfusion) in the same time window, iii. High risk etiologies of anemia: myelodysplastic syndromes, aplastic anemia, hemoglobinopathies (e.g., sickle cell trait, sickle cell anemia), anemia due to malignancy, anemia due to chronic kidney disease, anemia due to untreated nutritional deficiencies, anemia due to toxic exposures (e.g., chronic lead poisoning), or any other high-risk etiology as determined by the study investigator,

iv. Anemia with intensive recent (within 6 months) interventions, including red blood cell transfusion or IV iron infusion, v. Symptomatic anemia in the year prior to screening, including shortness of breath, exercise intolerance, type 3 myocardial infarction, if clearly attributed to the anemia.

• Participants who have precautions or contraindications to COVID-19 vaccine per the CDC interim clinical considerations for use of COVID-19 vaccines, including the following:

• History of a severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a component of the COVID-19 vaccine
• History of a diagnosed non-severe allergy to a component of the COVID-19 vaccine
• History of a non-severe, immediate (onset less than 4 hours) allergic reaction after administration of a previous dose of one COVID-19 vaccine type
• Moderate or severe acute illness, with or without fever
• History of multisystem inflammatory syndrome in adults
• History of myocarditis or pericarditis within 3 weeks after a dose of any COVID19 vaccine
• History of allergy or intolerance to Ta1.
• SARS-CoV-2 or other infection, during screening.
• SARS-CoV-2 mRNA or other SARS-CoV-2 vaccination during the previous 6 months.
• Participants who have dermatologic conditions that could affect local solicited adverse event (AE) assessment (e.g., psoriasis patches affecting skin over the sites of injection).
• Any medical condition that, in the judgement of the Investigator, could interfere with treatment or compliance with the protocol.
• Has received an investigational drug within the previous 30 days.