Anti-Interleukin-1 in Diabetes Action
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      A draw trial of the effect of Interleukin-1 Receptor Antagonist (anakinra, Kineret®) on the
      insulin production in patients with new onset Type 1 diabetes.

      Kineret® is already being used in the treatment of patients suffering from rheumatoid
      arthritis and preclinical studies are now suggesting that it may also be useful for patients
      with Type 1 diabetes. The active substance in Kineret is interleukin-1 receptor antagonist, a
      blocker of an immune-signal molecule named interleukin-1.

      The trial is a blinded randomised trial, in which the patient is allocated to receive the
      active drug (Kineret®) or placebo (saline). The hypothesis is that anti-IL-1 treatment as
      add-on therapy to conventional insulin therapy will preserve or enhance beta-cell function.
    

Detailed description: 
      Objectives:

      The aim of the Anti-Interleukin-1 in Diabetes Action trial (AIDA) study is to test the
      feasibility, safety/tolerability and potential efficacy of anti-IL-1 therapy in maintaining
      or enhancing beta-cell function in people with new onset Type 1 diabetes.

      Trial Design:

      A randomized, placebo controlled, double masked, parallel group, multicentre trial of IL-1
      antagonism in subjects with newly-diagnosed Type 1 diabetes. Patients are instructed to
      inject 100 mg human recombinant interleukin-1 receptor antagonist (anakinra, Kineret®, Amgen,
      CA) or placebo s.c. once daily for 2 years. Endpoints will be evaluated every three months,
      with an interim analysis after 6 months.

      Trial population:

      The design will be a two-stage phase 2a study to address feasibility, safety/tolerability and
      potential efficacy. In the first phase 80 patients between 18 and 35 years of age with new
      on-set Type 1 diabetes will be randomized to anakinra or placebo, and endpoints will be
      analyzed as an interim analysis after 6 months by an independent data and safety monitoring
      board (DSMB). A futility analysis will be performed at this time point to prevent
      continuation of the trial if it shows no likelihood of demonstrating efficacy. In the event
      the trial does show promise of efficacy considering the power of the first phase based on a
      conditional analysis the DSMB can recommend prolongation of the study with recruitment to
      ensure adequate power, and that additional funding is provided.

      Methods and interventions:

      The patients are instructed to administer anti-IL-1 therapy in the form of recombinant human
      non-glycosylated interleukin-1 receptor antagonist (anakinra) at a dose of 100 mg once daily
      or placebo by subcutaneous injection at the same time-point in the morning. Primary and
      secondary endpoints and safety parameters are investigated after 1 month and then every 3
      months.

      Safety:

      Anakinra is FDA approved for the indication rheumatoid arthritis and has an acceptable risk /
      benefit profile in this indication, with more than 100.000 patients treated. Most common
      ad-verse events include mild and transient local injection reactions in 20-50% of subjects
      treated with Anakinra. Consistent with its mechanism of action, anakinra reduces WBC/ANC in
      2.4% of patients and this may increase the risk of infection. Accordingly, treatment with
      anakinra will not be initiated in patients with active infections. Safety will be monitored
      by physical exams and blood and urine tests.
    

Intervention name(s): anakinra; saline
Intervention type(s): Drug; Drug
Intervention description(s): The patients are instructed to administer anti-IL-1 therapy in the form of recombinant human non-glycosylated interleukin-1 receptor antagonist (IL-1Ra, anakinra, Kineret®, Amgen, CA, USA) [13] at a dose of 100 mg once daily by subcutaneous injection; The patients are instructed to administer placebo (saline) once daily by subcutaneous injection
Other intervention name(s): Kineret
Intervention MeSH terms: Interleukin 1 Receptor Antagonist Protein
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: endogenous insulin production; C-peptide level; insulin requirement