A Pilot Trial of Thymalfasin (Ta1) to Prevent COVID-19 Infection in Renal Dialysis Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 189
- 试验地点
- 2
- 主要终点
- Reduction in documented infection with COVID-19 Reduction in infection with COVID-19
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Active arm
1.6 mg thymalfasin in 1 mL subcutaneous injection twice weekly after dialysis for 8 weeks
干预措施: Thymalfasin (Drug)
Control arm
Standard care
结局指标
主要结局
Reduction in documented infection with COVID-19 Reduction in infection with COVID-19
时间窗: 6 months
Number of subjects who become infected with COVID-19 over the course of the study
Number of Participants With COVID-19 Infection
时间窗: 6 months
Number of subjects who become infected with COVID-19 over the course of the study
次要结局
- ICU length of stay(6 months)
- Need for mechanical ventilation(6 months)
- Duration of mechanical ventilation(6 months)
- Recovery time from COVID-19(6 months)
- Change in any existing comorbidities or occurrence of newly diagnosed disease(6 months)
- Incidence of non-COVID-19 infections(6 months)
- Change in lymphocyte subsets (CD4, CD8)(6 months)
- Treatment-emergent adverse events(6 months)
- Need for hospitalization(6 months)
- Hospital length of stay(6 months)
- Need for ICU admission(6 months)
- Treatment-emergent changes in vital signs(6 months)
- Treatment-emergent laboratory parameters(6 months)
- Mortality(6 months)
- Hospitalization(6 months)
- Non-COVID-19 Infections(6 months)
研究者
William B. Ershler, MD
Hematology Consultant (Private)
Ershler, William B., MD