Anti-Cytokine Therapy for Hemodialysis InflammatION
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.
- End-Stage Renal Disease
- Eligible Ages
- Between 18 Years and 85 Years
- Eligible Genders
- Accepts Healthy Volunteers
- 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) >3 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
- 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
- Receipt of an investigational drug within the past 30 days
- Current or anticipated participation in another intervention study
- Phase 2
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
|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.||
|Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution.||
- Active, not recruiting
- University of Pennsylvania
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.