Clinical trial NCT04428008: Thymosin Alpha 1 to Prevent COVID-19 Infection in Renal Dialysis Patients
Official title: A Pilot Trial of Thymalfasin (Ta1) to Prevent COVID-19 Infection in Renal Dialysis Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: COVID-19
Keywords: COVID-19
Thymalfasin
Thymosin alpha 1
ZADAXIN
Hemodialysis
Lead sponsor: Ershler, William B., MD
Sponsor class: OTHER
Collaborators: name: Davita Clinical Research
name: Clinical Research Consultants, LLC
First posted: 2020-06-11
Enrollment: 262
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be centrally randomized to receive either study treatment drug (Ta1) or no Ta1. Randomization will be stratified by site.
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Reduction in documented infection with COVID-19 Reduction in infection with COVID-19
timeFrame: 6 months
Secondary outcomes:
measure: Need for hospitalization
timeFrame: 6 months
measure: Hospital length of stay
timeFrame: 6 months
measure: Need for ICU admission
timeFrame: 6 months
measure: ICU length of stay
timeFrame: 6 months
measure: Need for mechanical ventilation
timeFrame: 6 months
measure: Duration of mechanical ventilation
timeFrame: 6 months
measure: Recovery time from COVID-19
timeFrame: 6 months
measure: Change in any existing comorbidities or occurrence of newly diagnosed disease
timeFrame: 6 months
measure: Incidence of non-COVID-19 infections
timeFrame: 6 months
measure: Change in lymphocyte subsets (CD4, CD8)
timeFrame: 6 months
measure: Mortality
timeFrame: 6 months
measure: Treatment-emergent adverse events
timeFrame: 6 months
measure: Treatment-emergent changes in vital signs
timeFrame: 6 months
measure: Treatment-emergent laboratory parameters
timeFrame: 6 months
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: Clinical Research Consultants
state: Kansas
Study officials:
References: