Anti-Cytokine Therapy for Hemodialysis InflammatION (ACTION): A Phase II Multi-center Study to Evaluate the Safety and Tolerability of Anakinra, an IL-1 Receptor Antagonist, for Patients Treated With Maintenance Hemodialysis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 4
- 主要终点
- Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis
研究概览
简要总结
Anti-Cytokine Therapy for Hemodialysis InflammatION (ACTION) is a phase II multi-center study to evaluate the safety and tolerability of anakinra, an IL-1 receptor antagonist, for patients treated with maintenance hemodialysis.
详细描述
The ACTION Trial will enroll 80 participants being treated with maintenance hemodialysis for end-stage renal disease. Participants will be randomized to receive Anakinra, 100 mg administered intravenously 3 times per week at the end of the hemodialysis session, or matched placebo. The duration of study drug administration is 24 weeks. There will be an additional 24 weeks of follow-up after study drug administration has been completed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Maintenance hemodialysis therapy 3 times per week for end-stage renal disease
- •≥6 months since hemodialysis initiation
- •C-reactive protein measured by high sensitivity assay (hsCRP) ≥2.0 mg/L at screening and within 10 days prior to randomization
- •Most recent single pool Kt/V > or = 1.2 within 30 days prior to first screening visit
- •Negative tuberculosis interferon gamma release assay (e.g. Quantiferon-TB Gold) for tuberculosis unless documented treatment for a) positive PPD, b) positive interferon gamma release assay, or c) tuberculosis.
- •Negative human immunodeficiency virus (HIV) antibody test, negative hepatitis C Ab test unless viral clearance following direct antiviral therapy is documented, and negative hepatitis B surface antigen positivity.
- •For women of childbearing potential, willingness to use a highly effective method of birth control for up to 4 weeks after the last dose of anakinra.
- •Ability to provide informed consent
排除标准
- •Current or anticipated use of a hemodialysis central venous catheter
- •Acute bacterial infection, including vascular access infection, within 60 days prior to screening unless treated with antibiotics and resolved. Any chronic bacterial infection (e.g., osteomyelitis or bronchiectasis)
- •Hospitalization within 30 days unless for vascular access procedure
- •Malignancy within the past 5 years with exception of basal or squamous cell carcinoma
- •Use of an immunosuppressive drug within the past 3 months except low doses of oral corticosteroids (total daily dose ≤10 mg/day of prednisone or equivalent)
- •Receipt of live vaccine within the past 3 months. Live vaccines include Varicella zoster, measles, oral polio, rotavirus, yellow fever, and the nasal spray influenza vaccine
- •Absolute neutrophil count (ANC) <2,500 cells/mm3 (2.5 x 109 cells/L)
- •Platelet count <100,000/mm3 (100 x 109/L)
- •Known allergy to anakinra
- •Anticipated kidney transplantation, change to peritoneal dialysis, or transfer to another dialysis unit within 9 months
- •Expected survival less than 9 months
- •Pregnancy, anticipated pregnancy, or breastfeeding
- •Incarceration
- •Receipt of an investigational drug within the past 30 days
- •Current or anticipated participation in another intervention study
研究组 & 干预措施
Anakinra
Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra).
Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP.
干预措施: Anakinra (Drug)
Placebo
Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution.
干预措施: Placebo (Drug)
结局指标
主要结局
Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis
时间窗: 48 Weeks (after the 24-week treatment period and the 24-week post-treatment period)
The primary safety endpoint is serious adverse events per patient-year.
Change in Log-transformed Circulating CRP Concentration After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis
时间窗: Change from Baseline to 24 Weeks (end of treatment phase)
For this outcome, CRP measurements from Baseline and Week 24 were compared.
次要结局
- Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Infections(48 weeks)
- Change in Markers of Inflammation and Oxidative Stress - IL-6, pg/mL(change after 24 weeks of treatment)
- Change in Markers of Inflammation and Oxidative Stress - Albumin, g/dL(change after 24 weeks of treatment)
- Number of Participants With Adverse Events That Preclude Further Treatment With the Study Agent(24-week treatment period)
- Change in Markers of Inflammation and Oxidative Stress - IL-1β pg/ml(change after 24 weeks of treatment)
- Change in Markers of Inflammation and Oxidative Stress - IL-10, pg/mL(change after 24 weeks of treatment)
- Change in Markers of Inflammation and Oxidative Stress - TNF Alpha, pg/ml(change after 24 weeks of treatment)
- Change in Patient-reported Indicators of Depression After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis(24 Weeks (end of treatment phase))
- Change in Severity of Patient-reported Symptoms After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis(Change after 24 weeks of treatment)
- Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Neutropenia(48 weeks)
- Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Thrombocytopenia(48 weeks)
- Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Systemic Hypersensitivity Reactions(48 weeks)
- Change in Patient-reported Indicators of Fatigue After 24 Weeks of Treatment(24 Weeks (end of treatment phase))
- Change in Burden of Patient-reported Symptoms After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis(Change after 24 weeks of treatment)
- Change in Measure of Muscle Strength (Hand Grip Strength) After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis(24 Weeks (end of treatment phase))
- Change in Patient-reported Indicators of Quality of Life After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis(24 Weeks (end of treatment phase))