Anti-Cytokine Therapy for Hemodialysis InflammatION

NCT03141983 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 826900U01DK099919
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 4

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.

Conditions

End-Stage Renal Disease

Keywords

ESRD; End-Stage Kidney Disease

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis

  The primary safety endpoint is serious adverse events per patient-year.

  48 Weeks (after the 24-week treatment period and the 24-week post-treatment period)

• Change in Log-transformed Circulating CRP Concentration After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis

  For this outcome, CRP measurements from Baseline and Week 24 were compared.

  Change from Baseline to 24 Weeks (end of treatment phase)

Secondary Outcomes (16)

• Number of Participants With Adverse Events That Preclude Further Treatment With the Study Agent

  24-week treatment period

• Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Infections

  48 weeks

• Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Neutropenia

  48 weeks

• Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Thrombocytopenia

  48 weeks

• Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Systemic Hypersensitivity Reactions

  48 weeks

Study Arms (2)

Anakinra

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Anakinra DRUG

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.

Also known as: Kineret®

Anakinra

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Maintenance hemodialysis therapy 3 times per week for end-stage renal disease
• ≥6 months since hemodialysis initiation
• C-reactive protein measured by high sensitivity assay (hsCRP) ≥2.0 mg/L at screening and within 10 days prior to randomization
• Most recent single pool Kt/V \> or = 1.2 within 30 days prior to first screening visit
• 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.
• 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.
• 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.
• Ability to provide informed consent

You may not qualify if:

• Current or anticipated use of a hemodialysis central venous catheter
• 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)
• Hospitalization within 30 days unless for vascular access procedure
• Cirrhosis
• Malignancy within the past 5 years with exception of basal or squamous cell carcinoma
• 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)
• 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
• Absolute neutrophil count (ANC) \<2,500 cells/mm3 (2.5 x 109 cells/L)
• Platelet count \<100,000/mm3 (100 x 109/L)
• Known allergy to anakinra
• Anticipated kidney transplantation, change to peritoneal dialysis, or transfer to another dialysis unit within 9 months
• Expected survival less than 9 months
• Pregnancy, anticipated pregnancy, or breastfeeding
• Incarceration
• Receipt of an investigational drug within the past 30 days

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (4)

The George Washington University

Washington D.C., District of Columbia, 20037, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02120, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Washington Kidney Research Institute

Seattle, Washington, 98104, United States

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Natalie Kuzla
• Organization: University of Pennsylvania

nkuzla@pennmedicine.upenn.edu

2672524208

Study Officials

• Laura Dember, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2017
• First Posted: May 5, 2017
• Study Start: December 15, 2017
• Primary Completion: September 2, 2021
• Study Completion: September 2, 2021
• Last Updated: March 14, 2023
• Results First Posted: March 14, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share

Locations

US (4)