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Trial record 16 of 49 for:    Recruiting, Not yet recruiting, Available Studies | kidney disease | NIDDK

Anti-Cytokine Therapy for Hemodialysis InflammatION (ACTION)

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ClinicalTrials.gov Identifier: NCT03141983
Recruitment Status : Recruiting
First Posted : May 5, 2017
Last Update Posted : February 6, 2019
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
University of Pennsylvania

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
End-Stage Renal Disease Drug: Anakinra Drug: Placebo 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : December 15, 2017
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Anakinra

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 Name: 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.




Primary Outcome Measures :
  1. To evaluate the safety and tolerability of anakinra, for patients receiving maintenance hemodialysis [ Time Frame: 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

  2. Change in log-transformed circulating CRP concentration after 24 weeks of treatment for patients receiving maintenance hemodialysis [ Time Frame: 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 :
  1. Change in markers of inflammation and oxidative stress [ Time Frame: 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

  2. Change in circulating markers of cardiac disease between baseline and end of treatment [ Time Frame: 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

  3. Change in nutritional and metabolic markers after 24 weeks of treatment for patients receiving maintenance hemodialysis [ Time Frame: 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

  4. Change in patient-reported indicators of fatigue after 24 weeks of treatment for patients receiving maintenance hemodialysis [ Time Frame: 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

  5. Change in patient-reported indicators of depression after 24 weeks of treatment for patients receiving maintenance hemodialysis [ Time Frame: 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

  6. Change in patient-reported indicators of illness effects after 24 weeks of treatment for patients receiving maintenance hemodialysis [ Time Frame: 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

  7. Change in patient-reported symptoms after 24 weeks of treatment for patients receiving maintenance hemodialysis [ Time Frame: 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

  8. Change in patient-reported indicators of quality of life after 24 weeks of treatment for patients receiving maintenance hemodialysis [ Time Frame: 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

  9. Change in measure of muscle strength (hand grip strength) after 24 weeks of treatment for patients receiving maintenance hemodialysis [ Time Frame: 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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) >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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03141983


Contacts
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Contact: Laura Dember, MD 215-573-5264 dember@upenn.edu
Contact: Natalie Kuzla, MA 215-573-2935 nkuzla@upenn.edu

Locations
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United States, District of Columbia
The George Washington University Recruiting
Washington, District of Columbia, United States, 20037
Contact: Dominic Raj, MD    202-741-2283    draj@mfa.gwu.edu   
Contact: Sarah Andrews, BS    (202) 741-2571    scandrews@mfa.gwu.edu   
United States, Massachusetts
Brigham & Women's Hospital Recruiting
Boston, Massachusetts, United States, 02120
Contact: David Charytan, MD    617-525-7718    dcharytan@partners.org   
Contact: Angeles Cinelli, BA    (617) 525-9436    mcinelli@partners.org   
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Alp Ikizler, MD    615-343-6104    alp.ikizler@vanderbilt.edu   
Contact: Adrienne R Clagett, NP    (615) 875-5494    adrienne.r.clagett@vanderbilt.edu   
United States, Washington
University of Washington Kidney Research Institute Recruiting
Seattle, Washington, United States, 98104
Contact: Jonathan Himmelfarb, MD    206-616-4717    jhimmelfarb@nephrology.washington.edu   
Contact: Lori Linke    (206) 720-3835    llinke@nephrology.washington.edu   
Sponsors and Collaborators
University of Pennsylvania
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Laura Dember, MD University of Pennsylvania

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Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT03141983     History of Changes
Other Study ID Numbers: 826900
U01DK099919 ( U.S. NIH Grant/Contract )
First Posted: May 5, 2017    Key Record Dates
Last Update Posted: February 6, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Research results will be made available to the scientific community and public in a timely manner. The primary method by which data will be shared with the scientific community will be through peer-reviewed publications and presentation at scientific and professional society meetings. In addition, data and results will be submitted to the NIH in the annual progress reports required under the terms and conditions of the funding award. This study will also be registered with clinicaltrials.gov before initiation.

Data from the study will be submitted to the NIDDK Data Repository in accordance with the NIDDK Data Sharing policy. The policy requires that data sets be transferred no later than 2 years after study completion or 1 year after publication of the primary results, whichever comes first. Through the repository, the study data will be made available to external investigators.


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of Pennsylvania:
ESRD
End-Stage Kidney Disease
Additional relevant MeSH terms:
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Kidney Failure, Chronic
Inflammation
Pathologic Processes
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Interleukin 1 Receptor Antagonist Protein
Pharmaceutical Solutions
Antirheumatic Agents