Purpose

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.

Condition

Eligibility

Eligible Ages
Between 18 Years and 85 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Maintenance hemodialysis therapy 3 times per week for end-stage renal disease
  2. ≥6 months since hemodialysis initiation
  3. C-reactive protein measured by high sensitivity assay (hsCRP) >3 mg/L at screening and within 10 days prior to randomization
  4. Most recent single pool Kt/V > or = 1.2 within 30 days prior to first screening visit
  5. 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.
  6. 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.
  7. 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.
  8. Ability to provide informed consent

Exclusion Criteria

  1. Current or anticipated use of a hemodialysis central venous catheter
  2. 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)
  3. Hospitalization within 30 days unless for vascular access procedure
  4. Cirrhosis
  5. Malignancy within the past 5 years with exception of basal or squamous cell carcinoma
  6. 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)
  7. 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
  8. Absolute neutrophil count (ANC) <2,500 cells/mm3 (2.5 x 109 cells/L)
  9. Platelet count <100,000/mm3 (100 x 109/L)
  10. Known allergy to anakinra
  11. Anticipated kidney transplantation, change to peritoneal dialysis, or transfer to another dialysis unit within 9 months
  12. Expected survival less than 9 months
  13. Pregnancy, anticipated pregnancy, or breastfeeding
  14. Incarceration
  15. Receipt of an investigational drug within the past 30 days
  16. Current or anticipated participation in another intervention study

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
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.
  • Drug: Anakinra
    Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.
    Other names:
    • Kineret®
Placebo Comparator
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.
  • Drug: Placebo
    Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37232
Contact:
Alp Ikizler, MD
615-343-6104
alp.ikizler@vanderbilt.edu

More Details

NCT ID
NCT03141983
Status
Recruiting
Sponsor
University of Pennsylvania

Study Contact

Laura Dember, MD
215-573-5264
dember@upenn.edu

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.