Thymosin Alpha 1 to Prevent COVID-19 Infection in Renal Dialysis Patients (Ta1)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: Thymalfasin

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 262
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 64111
      • Clinical Research Consultants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active arm; 1.6 mg thymalfasin in 1 mL subcutaneous injection twice weekly after dialysis for 8 weeks	Drug: Thymalfasin; Synthetic 28 amino acid peptide; Other Names: Thymosin alpha 1; Ta1; ZADAXIN
No Intervention: Control arm; Standard care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for hospitalization	Number of subjects who become hospitalized	6 months
Hospital length of stay	If subject becomes hospitalized, what length of time does the subject remain hospitalized	6 months
Need for ICU admission	Number of subjects who are entered into the ICU	6 months
ICU length of stay	If subject is entered into the ICU, what length of time does the subject remain in the ICU	6 months
Need for mechanical ventilation	Number of subjects who require mechanical ventilation	6 months
Duration of mechanical ventilation	If mechanical ventilation is required, what length of time the ventilation is required	6 months
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
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
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
Change in lymphocyte subsets (CD4, CD8)	Evaluation of the levels of CD4 and CD8 subjects	6 months
Mortality	Number of subjects who die during the course of the study	6 months
Treatment-emergent adverse events	Number of subjects with mild, moderate, or severe adverse events based on perceived clinical significance of the event	6 months
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
Treatment-emergent laboratory parameters	Number of subjects with mild, moderate, or severe laboratory findings based on perceived clinical significance of the event	6 months

Collaborators and Investigators

• Sponsor: William B. Ershler, MD
• Collaborators: Davita Clinical Research; Clinical Research Consultants, LLC

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2021
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): February 1, 2023

Study Registration Dates

• First Submitted: June 7, 2020
• First Submitted That Met QC Criteria: June 10, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): September 27, 2022
• Last Update Submitted That Met QC Criteria: September 24, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; Hemodialysis; Thymalfasin; Thymosin alpha 1; ZADAXIN
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Thymalfasin
• Other Study ID Numbers: ACW-1221958-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No