Type II Diabetes Mellitus MedDRA version: 9.1 Level: LLT Classification code 10012601 Term: Diabetes mellitus
Conditions
Interventions
Product Name: Canakinumab
Product Code: ACZ885
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: canakinumab
Current Sponsor code: ACZ885
Concentration unit: mg milligram(s)
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must give written informed consent before any study related procedures are performed. 2. Patients must have a documented diagnosis of Type 2 diabetes confirmed by WHO criteria either a FPG= 7.0 mmol/l (126 mg/dl) or an OGTT test 2-hour PG = 11.1 mmol/l (200 mg/dl). 3. Patients must: • be naïve to anti-diabetes drug therapy (except for short term treatment courses with insulin in connection with hospitalization, etc.) • have an HbA1c between 7.5% and 11% (inclusive) at Screening analyzed by the Central Laboratory • be eligible for metformin monotherapy OR • be on stable metformin monotherapy treatment for at least three months at Screening • have an HbA1c between 7.0% and 9% (inclusive) at Screening analyzed by the Central Laboratory • take metformin as their first and only treatment with anti-diabetes drug therapy (except for short term treatment courses with insulin in connection with hospitalization, etc.) OR • be taking an a-glucosidase inhibitor as their first and only treatment with antidiabetes drug therapy (except for short term treatment courses with insulin in connection with hospitalization, etc.) • have the a-glucosidase inhibitor stopped and be washed out from the a-glucosidase inhibitor for at least a week prior to Run-in • have an HbA1c between 7.0% and 9.0% (inclusive) at Screening analyzed by the Central Laboratory • be eligible for metformin monotherapy 4. Patients must have a morning fasting plasma glucose result =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Type 1 diabetes, diabetes that is a result of pancreatic injury or secondary forms of diabetes, e.g. Cushing’s syndrome and acromegaly. 2. Any of the following significant laboratory abnormalities: • Serum GAD-antibody positivity analyzed by the Central Laboratory. • Clinically significant TSH outside of normal range at Screening analyzed by the Central Laboratory. • 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) at Screening. • Total bilirubin >2 times ULN and/or direct bilirubin greater than the ULN at Screening. 3. Known chronic liver disease of any aetiology. 4. History or current findings of active pulmonary disease (e.g. tuberculosis, fungal diseases) as evidenced by any of the following: • History of positive PPD skin test result followed by positive chest x-ray/positive QFT-G test and no completion of treatment. • A positive PPD skin test followed by a positive chest x-ray or positive QFT(-G) test (with or without positive chest x-ray) during the screening period. • History of a positive QFT(-G) test and no completion of treatment. • History of a positive AFB sputum sample and no completion of treatment. • Requirement for administration of antibiotics against latent tuberculosis (e.g., isoniazide). Courses of antibiotic therapy started prior to entering the study should not be prematurely terminated to allow inclusion into the study. 5. One of the risk factors for TB such as: • History of any of the following: residence in a congregate setting (e.g. jail or prison, homeless shelter, or chronic care facility), substance abuse (e.g. injection or noninjection); health-care workers with unprotected exposure to patients who are at high risk of TB or patients with TB disease before the identification and correct airborne precautions of the patient, or • Close contact (i.e. share the same air space in a household or other enclosed environment for a prolonged period (days or weeks, not minutes or hours)) with a person with active pulmonary TB disease. 6. 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 immunocompromisation, including patients with evidence of Human Immunodeficiency Virus (HIV) infection. 7. Known presence or suspicion of active or recurrent Hepatitis B and Hepatitis C infections (based on history and/or findings from the Central Lab). 8. Any surgical or underlying hepatic, hematologic, pulmonary, infectious, autoimmune or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and/or places the patient at unacceptable risk for participation in immunodulatory therapy. 9. Any systemic treatment or local treatment of any immune modulating agent in doses with systemic effects. 10. Live vaccinations within 3 months prior to the Randomization Visit or live vaccinations planned during the trial and up to three months following the last dose. 11. Stroke, myocardial infarction, acute coronary syndrome, revascularization procedure or recurrent TIA within the last 6 months. 12. Unwillingness to use insulin glargine as the additional medication should glycemic control deteriorate. 13. Use of other investigational drugs at the time of enro
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: For Period II • To assess safety and tolerability of four doses of ACZ885 (5 mg, 15 mg, 50 mg, and 150 mg) vs. placebo as an add-on regimen over 4 months. • To assess the effect on HbA1c of four doses of ACZ885 (5 mg, 15 mg, 50 mg, and 150 mg) vs. placebo as an add-on regimen over 4 months. For Period III • To assess the anti-apoptotic effect of ACZ885 vs. placebo on the meal challenge derived dynamic phase secreted insulin per unit of glucose concentration in patients who have been on study drug anywhere from 6 months to 18 months. For Period IV • To assess the safety and tolerability of active treatment of ACZ885 vs. placebo, as an add-on regimen over a minimum of 24 months (up to 48 months) period.;Secondary Objective: For Period II: • To evaluate the effect of 4-month treatment of ACZ885 at doses 5 mg, 15 mg, 50 mg, and 150 mg vs. placebo on the following variables: • Area under the curve (AUC) and peak values of C-peptide following meal test • Area under the curve (AUC), 2-hour value and peak value of glucose and insulin following meal test • Insulin secretion rate derived based on glucose and C-peptide following meal test • Average and peak values based on 7-point glucose meter data For Period IV: • To evaluate the effect of long-term treatment of ACZ885 at the dose selected based on the efficacy and safety data from the 4-month treatment period vs. placebo on the following variables: • Duration of insulin use and insulin dose • Area under the curve (AUC) and peak values of C-peptide following meal test • Area under the curve (AUC), 2-hour value and peak value of glucose and insulin following meal test For detailed list see full protocol ;Primary end point(s): The primary efficacy variable for the dose finding period (Period II) is the change from baseline in HbA1c at Month 4. | — |
Countries
Belgium, Germany, Hungary, United Kingdom
Outcome results
None listed