NCT00711503

Anti-Interleukin-1 in Diabetes Action

A Randomised Clinical Trial of the Effect of Interleukin-1 Receptor Antagonism on the Insulin Production in Patients With New Onset Type 1 Diabetes

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 69 (actual)
• Sponsor: Steno Diabetes Center Copenhagen · Academic / Other
• Sex: All
• Age: 18 Years – 35 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Type 1 Diabetes

Interventions

Type	Name	Description
DRUG	anakinra	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
DRUG	saline	The patients are instructed to administer placebo (saline) once daily by subcutaneous injection

Timeline

• Start date: 2009-01-01
• Primary completion: 2012-01-01
• Completion: 2012-06-01
• First posted: 2008-07-09
• Last updated: 2012-09-03

Locations

17 sites across 7 countries: Denmark, Germany, Italy, Netherlands, Poland, Spain, Switzerland