ACTION: Anti-Cytokine Therapy for Hemodialysis InflammatION
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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:
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| 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.
|
Outcome Measures
Primary Outcome Measures
- To evaluate the safety and tolerability of anakinra, for patients receiving maintenance hemodialysis [48 Weeks (after the 24-week treatment period and the 24-week post-treatment period)]
The safety endpoints are: 1) adverse events, 2) adverse events that preclude further treatment with the study agent, 3) infections, 4) neutropenia, 5) thrombocytopenia, 6) systemic hypersensitivity reactions
- Change in log-transformed circulating CRP concentration after 24 weeks of treatment for patients receiving maintenance hemodialysis [28 Weeks (after 24 weeks of treatment and the first follow-up measure at Week 28, 4 weeks into the post-treatment phase)]
CRP is measured at 2 screening visits, the Baseline Visit, at 4 week intervals during the treatment phase and at Week 28.
Secondary Outcome Measures
- Change in markers of inflammation and oxidative stress [28 Weeks (after 24 weeks of treatment and the first follow-up measure at Week 28, 4 weeks into the post-treatment phase)]
Change in circulating markers of inflammation and oxidative stress between baseline and end of treatment
- Change in circulating markers of cardiac disease between baseline and end of treatment [28 Weeks (after 24 weeks of treatment and the first follow-up measure at Week 28, 4 weeks into the post-treatment phase)]
Change in circulating markers of cardiac disease between baseline and end of treatment
- Change in nutritional and metabolic markers after 24 weeks of treatment for patients receiving maintenance hemodialysis [28 Weeks (after 24 weeks of treatment and the first follow-up measure at Week 28, 4 weeks into the post-treatment phase)]
Change in circulating nutritional and metabolic markers between baseline and end of treatment
- Change in patient-reported indicators of fatigue after 24 weeks of treatment for patients receiving maintenance hemodialysis [28 Weeks (after 24 weeks of treatment and the first follow-up measure at Week 28, 4 weeks into the post-treatment phase)]
Change in patient reported outcomes using the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale at baseline, Weeks 12, 24 and 28
- Change in patient-reported indicators of depression after 24 weeks of treatment for patients receiving maintenance hemodialysis [28 Weeks (after 24 weeks of treatment and the first follow-up measure at Week 28, 4 weeks into the post-treatment phase)]
Change in patient reported outcomes using the Beck Depression Inventory - II (BDI-II) scale at baseline, Weeks 12, 24 and 28
- Change in patient-reported indicators of illness effects after 24 weeks of treatment for patients receiving maintenance hemodialysis [28 Weeks (after 24 weeks of treatment and the first follow-up measure at Week 28, 4 weeks into the post-treatment phase)]
Change in patient reported outcomes using the Illness Effects Questionnaire (IEQ) at baseline, Weeks 12, 24 and 28
- Change in patient-reported symptoms after 24 weeks of treatment for patients receiving maintenance hemodialysis [28 Weeks (after 24 weeks of treatment and the first follow-up measure at Week 28, 4 weeks into the post-treatment phase)]
Change in patient reported outcomes using the Dialysis Symptom Index at baseline, Weeks 12, 24 and 28
- Change in patient-reported indicators of quality of life after 24 weeks of treatment for patients receiving maintenance hemodialysis [28 Weeks (after 24 weeks of treatment and the first follow-up measure at Week 28, 4 weeks into the post-treatment phase)]
Change in patient reported outcomes using the Kidney Disease - Quality of Life subscale of the SF-12 (KDQOL SF-12) at baseline, Weeks 12, 24 and 28
- Change in measure of muscle strength (hand grip strength) after 24 weeks of treatment for patients receiving maintenance hemodialysis [28 Weeks (after 24 weeks of treatment and the first follow-up measure at Week 28, 4 weeks into the post-treatment phase)]
Change in measurement of hand grip strength using a standard dynamometer at baseline, Weeks 12, 24 and 28
Eligibility Criteria
Criteria
Inclusion Criteria:
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Maintenance hemodialysis therapy 3 times per week for end-stage renal disease
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≥6 months since hemodialysis initiation
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C-reactive protein measured by high sensitivity assay (hsCRP) ≥2.0 mg/L at screening and within 10 days prior to randomization
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Most recent single pool Kt/V > or = 1.2 within 30 days prior to first screening visit
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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.
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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.
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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.
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Ability to provide informed consent
Exclusion Criteria:
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Current or anticipated use of a hemodialysis central venous catheter
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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)
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Hospitalization within 30 days unless for vascular access procedure
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Cirrhosis
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Malignancy within the past 5 years with exception of basal or squamous cell carcinoma
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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)
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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
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Absolute neutrophil count (ANC) <2,500 cells/mm3 (2.5 x 109 cells/L)
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Platelet count <100,000/mm3 (100 x 109/L)
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Known allergy to anakinra
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Anticipated kidney transplantation, change to peritoneal dialysis, or transfer to another dialysis unit within 9 months
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Expected survival less than 9 months
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Pregnancy, anticipated pregnancy, or breastfeeding
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Incarceration
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Receipt of an investigational drug within the past 30 days
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Current or anticipated participation in another intervention study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The George Washington University | Washington | District of Columbia | United States | 20037 |
| 2 | Brigham & Women's Hospital | Boston | Massachusetts | United States | 02120 |
| 3 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232 |
| 4 | University of Washington Kidney Research Institute | Seattle | Washington | United States | 98104 |
Sponsors and Collaborators
- University of Pennsylvania
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
- Principal Investigator: Laura Dember, MD, University of Pennsylvania
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 826900
- U01DK099919