Dose Finding, Safety and Efficacy of Monthly Subcutaneous Canakinumab Administration in Metformin Monotherapy Treated Type 2 Diabetic Patients

Summary

This was a four month dose ranging study followed by a 24 to 48 month extension at the selected dose to characterize the safety and efficacy of the injectable IL-1B (interleukin 1, beta) antagonist canakinumab in the treatment of patients with Type 2 diabetes mellitus (T2DM) already treated on maximum dose metformin.

Timeline

Start

2009-04

Primary completion

2010-11

Completion

2010-11

Outcome

Missed primary endpoint

Stopped: “Numerically modest lowering of HbA1c with canakinumab in combination with metformin was inadequate to continue patients with T2DM into Period IV of this study.”

paper with maximal effect noted in the 50mg dose of canakinumab (-0.18% difference vs placebo; multiplicity-adjusted, P=0.13902) PMID 24075453 ↗

Publications

• Noe A, Howard C, Thuren T, Taylor A, Skerjanec A. Pharmacokinetic and pharmacodynamic characteristics of single-dose Canakinumab in patients with type 2 diabetes mellitus. Clin Ther. 2014 Nov 1;36(11):1625-37. doi: 10.1016/j.clinthera.2014.08.004. Epub 2014 Sep 18.
• Hensen J, Howard CP, Walter V, Thuren T. Impact of interleukin-1beta antibody (canakinumab) on glycaemic indicators in patients with type 2 diabetes mellitus: results of secondary endpoints from a randomized, placebo-controlled trial. Diabetes Metab. 2013 Dec;39(6):524-31. doi: 10.1016/j.diabet.2013.07.003. Epub 2013 Sep 25.
• Ridker PM, Howard CP, Walter V, Everett B, Libby P, Hensen J, Thuren T; CANTOS Pilot Investigative Group. Effects of interleukin-1beta inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb randomized, placebo-controlled trial. Circulation. 2012 Dec 4;126(23):2739-48. doi: 10.1161/CIRCULATIONAHA.112.122556. Epub 2012 Nov 5.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Canakinumab	Monoclonal antibody	5 mg	Subcutaneous
Subject	Canakinumab	Monoclonal antibody	15 mg	Subcutaneous
Subject	Canakinumab	Monoclonal antibody	50 mg	Subcutaneous
Subject	Canakinumab	Monoclonal antibody	150 mg	Subcutaneous
Background	Metformin	Small molecule	500 mg	—
Background	Metformin	Small molecule	1000 mg	—

Indications