Thymosin Alpha 1 to Prevent COVID-19 Infection in Renal Dialysis Patients

COVID-19 Clinical Trial

— Ta1  

Official title:

A Pilot Trial of Thymalfasin (Ta1) to Prevent COVID-19 Infection in Renal Dialysis Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04428008
• Other study ID #: ACW-1221958-1
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 12, 2021
• Est. completion date: February 2023

Study information

• Verified date: September 2022
• Source: Ershler, William B., MD
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Thymalfasin (thymosin alpha 1 or Ta1), the active pharmaceutical ingredient in ZADAXIN® injection, is a 28-amino acid synthetic peptide, identical to natural Ta1 produced by the thymus gland. Ta1 is a biological response modifier which activates various cells of the immune system, and is therefore expected to have clinical benefits in disorders where immune responses are impaired or ineffective, including acute and chronic viral and bacterial infections, cancers, and vaccine non-responsiveness. Patients with end-stage renal disease (ESRD) on hemodialysis, in addition to their intrinsic kidney disease and frequent burden of comorbidities, also have increased risk of exposure to communicable diseases as they are treated several times each week at hemodialysis centers with several other patients and clinic staff in attendance. The majority of patients are over 60 years of age and many are receiving immunosuppressive medications. Accordingly, ESRD patients are particularly susceptible to COVID-19 infection. Ta1 has been shown to be safely administered to hemodialysis patients. It is our hypothesis that a course of Ta1 administered to individuals with ESRD will reduce the rate and severity of infection with COVID-19.

Description:

Patients with end-stage renal disease (ESRD) on hemodialysis, in addition to their intrinsic kidney disease and frequent burden of comorbidities, also have increased risk of exposure to communicable diseases as they are treated several times each week at hemodialysis centers with several other patients and clinic staff in attendance. The majority of patients are over 60 years of age and many are receiving immunosuppressive medications. Accordingly, ESRD patients are particularly susceptible to COVID-19 infection.

Thymalfasin (thymosin alpha 1, Ta1) is a naturally occurring peptide that has been evaluated for its immunomodulatory activities and related therapeutic potential in several conditions and diseases, including infectious disease and cancer. ZADAXIN, a synthetic form of Ta1, been has been used clinically in pilot studies for treatment of severe acute respiratory syndrome (SARS) and other lung infections including acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disorder (COPD), as well as infections after bone marrow transplant]. Larger clinical trials have shown significant efficacy for treatment of severe sepsis and hepatitis B, along with certain cancers such as melanoma, hepatocellular, and lung cancer. Ta1 has also demonstrated improvement in response to vaccines in the elderly and in patients immunocompromised by renal disease. The beneficial clinical effects of Ta1 result from activation of toll-like receptor (TLR) 9 in dendritic and other immune system cells, resulting in augmentation of T helper (Th1) function, natural killer (NK) cell activity, and increased antibody responses to T-cell dependent antigens. Importantly, Ta1 also leads to an increase in IL-10 producing regulatory T cells, which create feedback inhibition of cytokine production, hence dampening immune response and preventing a pro-inflammatory cytokine storm.

It is our hypothesis that a course of Ta1 administered to individuals at high risk for COVID-19 infection (hemodialysis patients) will reduce the rate of COVID-19 infection and severity of infection with COVID-19, compared to untreated individuals in the same hemodialysis units with comparable risk. The study will also evaluate the need for hospitalization in those patients who do not become infected with COVID-19.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 262
• Est. completion date: February 2023
• Est. primary completion date: October 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

• Age 18 or greater

• Signed informed consent

• End-stage renal disease (ESRD) who receive hemodialysis 2 or more times each week and are expected to continue on dialysis indefinitely.

Exclusion Criteria:

• Patients on short-term hemodialysis, such as those with transient renal dysfunction associated with acute illness who are projected to have return in renal function

• Patients for whom renal transplantation is anticipated within the next six months

• Patients with an anticipated survival of less than 3 months

• Patients with symptoms that might be attributable to COVID-19 infection

• Patients who test positive for SARS-CoV2

• Patients with active infectious disease requiring antibiotics

• Patients with hospitalization within the previous 3 months for acute myocardial infarction or congestive heart failure

• Patients with advanced malignancy receiving cytotoxic chemotherapy

• Patients with a Karnofsky Performance Scale score of less than 60

• Patients with prior history of solid organ (kidney, liver, heart, lung, pancreas) or bone marrow transplant

• Patients with active autoimmune disease on immunosuppressive medication

• Patients receiving Plaquenil

• Participation in an investigational drug or device trial in previous 30 days

• History of allergy or intolerance to Ta1

• Any other medical or psychiatric condition that, in the opinion of the Investigator, would compromise patient safety or interfere with the objectives of the protocol or completion of the protocol treatment

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Thymalfasin
Synthetic 28 amino acid peptide

Locations

Country	Name	City	State
United States	Clinical Research Consultants	Kansas City	Kansas

Sponsors (3)

Lead Sponsor	Collaborator
William B. Ershler, MD	Clinical Research Consultants, LLC, Davita Clinical Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in documented infection with COVID-19 Reduction in infection with COVID-19	Number of subjects who become infected with COVID-19 over the course of the study	6 months
Secondary	Need for hospitalization	Number of subjects who become hospitalized	6 months
Secondary	Hospital length of stay	If subject becomes hospitalized, what length of time does the subject remain hospitalized	6 months
Secondary	Need for ICU admission	Number of subjects who are entered into the ICU	6 months
Secondary	ICU length of stay	If subject is entered into the ICU, what length of time does the subject remain in the ICU	6 months
Secondary	Need for mechanical ventilation	Number of subjects who require mechanical ventilation	6 months
Secondary	Duration of mechanical ventilation	If mechanical ventilation is required, what length of time the ventilation is required	6 months
Secondary	Recovery time from COVID-19	If subject becomes infected with COVID-19, how long does the subject require to recover from the infection	6 months
Secondary	Change in any existing comorbidities or occurrence of newly diagnosed disease	Evaluation of whether any comorbidities are changed over the course of treatment (eg., worsening of congestive heart failure)	6 months
Secondary	Incidence of non-COVID-19 infections	Determination of whether there are more or fewer infections other than COVID-19 (other respiratory, urinary tract, cellulitis, etc.)	6 months
Secondary	Change in lymphocyte subsets (CD4, CD8)	Evaluation of the levels of CD4 and CD8 subjects	6 months
Secondary	Mortality	Number of subjects who die during the course of the study	6 months
Secondary	Treatment-emergent adverse events	Number of subjects with mild, moderate, or severe adverse events based on perceived clinical significance of the event	6 months
Secondary	Treatment-emergent changes in vital signs	Number of subjects with mild, moderate, or severe changes to vital signs based on perceived clinical significance of the event	6 months
Secondary	Treatment-emergent laboratory parameters	Number of subjects with mild, moderate, or severe laboratory findings based on perceived clinical significance of the event	6 months