Safety, pharmacokinetics, and preliminary efficacy of a specific anti-IL-1alpha therapeutic antibody (MABp1) in patients with type 2 diabetes mellitus

AIMS: The role of the IL-1 system in development of type 2 diabetes is well established. Using an IL-1 receptor antagonist, which blocks IL-1alpha and -beta activity, or by specifically neutralizing IL-1beta, several clinical studies have demonstrated improvement in insulin secretion and glycaemia. However, the role of IL-1alpha remains to be investigated. METHODS: We evaluated the safety and preliminary efficacy of a neutralizing true human monoclonal antibody against IL-1alpha (MABp1) in an open label trial in patients with type 2 diabetes. Seven patients between 50 to 66years with type 2 diabetes mellitus were enrolled in the study. The study subjects received four biweekly intravenous infusions of MABp1 at 1.25mg/kg body weight up to day 60 and were followed up for a total of 90days. RESULTS: Compared to baseline, after the 60-day period of treatment HbA1c was numerically reduced by 0.14+/-0.21% (p=0.15), fasting C-peptide was increased by 88% (p=0.03), pro-insulin by 48% (p=0.03) and insulin numerically increased by 74% (p=0.11). Systolic blood pressure numerically decreased by 11mmHg (p=0.2). Both HbA1c and blood pressure rebounded to baseline levels thirty days after the end of MABp1 application. Treatment with MABp1 was well tolerated, and no adverse events occurred during the study. CONCLUSION: The results point to a role of IL-1alpha in type 2 diabetes and encourage further investigations. (ClinicalTrials.gov number NCT01427699)