Anti-Interleukin-1 in Diabetes Action

Type 1 Diabetes Clinical Trial

— AIDA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00711503
• Other study ID #: 2007-007146-34
• Secondary ID: EudraCT 2007-007
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: July 3, 2008
• Last updated: August 31, 2012
• Start date: January 2009
• Est. completion date: June 2012

Study information

• Verified date: August 2012
• Source: Steno Diabetes Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: June 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Type 1 diabetes diagnosed according to WHO 1999 criteria

• Positive GAD auto-antibodies

• Age 18-35 yrs at onset of diabetes

• Time from first symptoms of diabetes < 12 weeks

• Peak C-peptide more than or equal to 200 pM after a standardized mixed meal test (Boost) at a test carried out when the subject is metabolically stable, i.e. after resolution of any polyuria, polydypsia or ketoacidosis.

Exclusion Criteria:

• Severe liver or renal disease (creatinine > 100 µmol/L, ASAT/ALAT > 2* ULN, alkaline phosphatase > 2 * ULN)

• History of heart disease, signs of cardiac failure or abnormal ECG

• Present or previous malignancy

• Pregnancy or failure of fertile female to comply with contraceptional planning, or breast-feeding. (Safe contraceptive methods include birth control pills, IUD, and gestagen implants) . Plans of pregnancy within 2 years.

• Participation in other clinical intervention studies

• Anti-inflammatory therapy (except aspirin £ 100 mg/d)

• Active infections (CRP>30), history of recurrent infection or predisposition to infections

• Neutropenia: ANC < 1.5*109/L, or anaemia: Haemoglobin < 8.0 g/dL

• Immune-suppressive treatment or immune-deficiency

• Presence at diagnosis of late diabetic complications

• Concurrent vaccination with live vaccine. Known need for live vaccinations within 2 years.

• Use of Etanercept within 6 months before screening or during the double-blinded study period

• Hypersensitivity to E. coli-derived proteins, anakinra or any components of the product.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

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
• saline
The patients are instructed to administer placebo (saline) once daily by subcutaneous injection

Locations

Country	Name	City	State
Denmark	Aalborg Hospital	Aalborg
Denmark	Aarhus Universitetshospital	Aarhus
Denmark	Bispebjerg Universitetshospital	Copenhagen
Denmark	Steno Diabetes Center	Gentofte
Denmark	Nordsjællands Hospital, Hillerød	Hillerød
Germany	Leibniz Center for Diabetes research, Heinrich-Heine University	Duesseldorf
Germany	University of Frankfurt am Main	Frankfurt am Main
Germany	Institut für Diabetesforschung, Munich University of Technology	Munich
Germany	Ulm University, Dept. of Internal Medicine	Ulm	Donau
Italy	University Campus Bio-Medico	Rome
Netherlands	Leiden University Medical Center	Leiden
Poland	Medical University of Bialystok	Bialystok
Spain	Hospital de Cruces, Diabetes Research Group	Barakaldo	Bizkaia
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Hospital Unversitario Insular de Gran Canaria	Las Palmas	Gran Canaria
Spain	Hospital Arnua de Vilanova	Lleida
Switzerland	University Hospital Zürich	Zürich

Sponsors (3)

Lead Sponsor	Collaborator
Steno Diabetes Center	Juvenile Diabetes Research Foundation, Oeresund Diabetes Academy

Countries where clinical trial is conducted

Denmark,  Germany,  Italy,  Netherlands,  Poland,  Spain,  Switzerland, 

References & Publications (1)

Pickersgill LM, Mandrup-Poulsen TR. The anti-interleukin-1 in type 1 diabetes action trial--background and rationale. Diabetes Metab Res Rev. 2009 May;25(4):321-4. doi: 10.1002/dmrr.960. Review. Erratum in: Diabetes Metab Res Rev. 2009 Nov;25(8):780. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	? 2-h AUC C-peptide response		1 month, 3 months, 6 months, 9 months	No
Secondary	Incremental and/or peak C-peptide response, Time to peak C-peptide, insulin requirement per kg body weight per day,frequency of insulin free state with maintenance of HbA1c <7.5%, HbA1c, Means of fasting glucose values, circulating IL-6 and CRP		1 month, 3 months, 6 months, 9 months	No