Clinical trial NCT03141983: Anti-Cytokine Therapy for Hemodialysis InflammatION
Official title: Anti-Cytokine Therapy for Hemodialysis InflammatION (ACTION): 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: End-Stage Renal Disease
Keywords: ESRD
End-Stage Kidney Disease
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2017-05-05
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis
timeFrame: 48 Weeks (after the 24-week treatment period and the 24-week post-treatment period)
measure: Change in Log-transformed Circulating CRP Concentration After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis
timeFrame: Change from Baseline to 24 Weeks (end of treatment phase)
Secondary outcomes:
measure: Number of Participants With Adverse Events That Preclude Further Treatment With the Study Agent
timeFrame: 24-week treatment period
measure: Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Infections
timeFrame: 48 weeks
measure: Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Neutropenia
timeFrame: 48 weeks
measure: Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Thrombocytopenia
timeFrame: 48 weeks
measure: Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Systemic Hypersensitivity Reactions
timeFrame: 48 weeks
measure: Change in Markers of Inflammation and Oxidative Stress - IL-1β pg/ml
timeFrame: change after 24 weeks of treatment
measure: Change in Markers of Inflammation and Oxidative Stress - IL-6, pg/mL
timeFrame: change after 24 weeks of treatment
measure: Change in Markers of Inflammation and Oxidative Stress - IL-10, pg/mL
timeFrame: change after 24 weeks of treatment
measure: Change in Markers of Inflammation and Oxidative Stress - TNF Alpha, pg/ml
timeFrame: change after 24 weeks of treatment
measure: Change in Markers of Inflammation and Oxidative Stress - Albumin, g/dL
timeFrame: change after 24 weeks of treatment
measure: Change in Patient-reported Indicators of Fatigue After 24 Weeks of Treatment
timeFrame: 24 Weeks (end of treatment phase)
measure: Change in Patient-reported Indicators of Depression After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis
timeFrame: 24 Weeks (end of treatment phase)
measure: Change in Burden of Patient-reported Symptoms After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis
timeFrame: Change after 24 weeks of treatment
measure: Change in Severity of Patient-reported Symptoms After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis
timeFrame: Change after 24 weeks of treatment
measure: Change in Patient-reported Indicators of Quality of Life After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis
timeFrame: 24 Weeks (end of treatment phase)
measure: Change in Measure of Muscle Strength (Hand Grip Strength) After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis
timeFrame: 24 Weeks (end of treatment phase)
Other outcomes:
Locations:
city: Washington
country: United States
facility: The George Washington University
state: District of Columbia
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Seattle
country: United States
facility: University of Washington Kidney Research Institute
state: Washington
Study officials:
affiliation: University of Pennsylvania
name: Laura Dember, MD
role: PRINCIPAL_INVESTIGATOR
References: