Anti-Cytokine Therapy for Hemodialysis InflammatION (ACTION)

University of Pennsylvania

Status and phase: Completed; Phase 2

Conditions: End-Stage Renal Disease

Treatments: Drug: Anakinra; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03141983

826900

U01DK099919 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 80 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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) ≥2.0 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 2 patient groups, including a placebo group

Anakinra

Active Comparator group

Description:

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.

Treatment:

Drug: Anakinra

Placebo

Placebo Comparator group

Description:

Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution.

Treatment:

Drug: Placebo