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

Dose Finding, Safety and Efficacy of Monthly Subcutaneous Canakinumab Administration for the Treatment of Hyperglycemia in Metformin Monotherapy Treated Type 2 Diabetic Patients: a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study

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.

Inclusion Criteria:

1. Patients must have a documented diagnosis of Type 2 diabetes confirmed by World Health Organization (WHO) criteria either a FPG≥ 7.0 mmol/l (126 mg/dl) or an Oral glucose tolerance test (OGTT) test 2-hour PG ≥ 11.1 mmol/l (200 mg/dl).

2. Patients must:

   • be naïve to anti-diabetes drug therapy (except for short term treatment courses with insulin in connection with hospitalization, etc.)
   • meet protocol specified Glycosylated hemoglobin / hemoglobin A1c (HbA1c) criteria
   • be eligible for metformin monotherapy OR
   • be on stable metformin monotherapy treatment for at least three months at Screening
   • meet protocol specified HbA1c criteria
   • take metformin as their first and only treatment with anti-diabetes drug therapy OR
   • be taking an AGI as their first and only anti-diabetes drug therapy (except short term treatment courses with insulin in connection with hospitalizations, etc)
   • meet protocol specified HbA1c criteria
   • be eligible for metformin monotherapy

3. Patients must have a morning fasting plasma glucose result < 180 mg/dl at Visit 3 (Month -1) analyzed by the Central Laboratory.

4. Were on a daily dose of metformin ≥ 1000 mg (or less according to local regulations)

Exclusion Criteria:

1. Type 1 diabetes, diabetes resulting from pancreatic injury or secondary forms of diabetes.

2. Any of the following significant laboratory abnormalities:

   • Serum Glutamic acid decarboxylase (GAD)-antibody positivity
   • Clinically significant Thyroid stimulating hormone (TSH) outside of normal range at Screening
   • Renal function indicating high risk metformin use, including serum creatinine concentrations (≥1.5 mg/dL for males, ≥1.4 mg/dL for females) or other evidence of abnormal creatinine clearance.
   • Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN), or total bilirubin > 2 x ULN and/or direct bilirubin > ULN at Screening, confirmed with repeat measure within one week.

3. History or current findings of active pulmonary disease as evidenced by a history of positive purified protein derivative (PPD), QuantiFERON-TB Gold (QFT-G), AFB sputum or positive PPD followed by positive chest x-ray or QFT-G, or ongoing antibiotic treatment for latent TB.

4. Risk factors for TB as defined in protocol

5. Known presence or suspicion of active or recurrent bacterial, fungal or viral infection at the time of enrollment proven or suspected to be related to immunocompromise including HIV or active or recurrent Hepatitis B and Hepatitis C.

6. Systemic or local treatment of any immune modulating agent in doses with systemic effects or live vaccinations within 3 months

7. Stroke, myocardial infarction, acute coronary syndrome, revascularization procedure or recurrent TIA within the last 6 months.

8. Unwillingness to use insulin glargine as the additional medication should glycemic control deteriorate.

Other protocol-defined inclusion/exclusion criteria may apply