Anti-Cytokine Therapy for Hemodialysis InflammatION

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.

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