A Randomized Double Blind, Placebo Controlled Trial With AMG 108 in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effects of blocking IL-1 signaling with AMG 108 in type 2 diabetes mellitus patients on glycemic control, as measured by change in HbA1c from baseline to end of treatment (EOT).

Official Title
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A Mutiple Dose, Randomized, Double-blind, Placebo-controlled Study of Subcutaneous AMG 108 in Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Biological: AMG 108
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of T2DM ≥ 3 months at time of randomization HbA1c of 7.0 - 9.5% (inclusive) at screening ≥ 18 years of age at the time of randomization BMI ≥ 25 kg/m2 and ≤ 45 kg/m2 at screening, and, per patient self-report, following their regular weight maintenance or reduction diet for the management of diabetes for at least 4 weeks prior to randomization Fasting plasma glucose ≤ 240 mg/dL (13.3 mmol/L) at each of 2 determinations during screening (samples taken at least 1 day apart) No new therapy for the treatment of elevated blood pressure or dyslipidemia, use of any weight loss medication (over the counter or prescription), or initiation of a prescribed weight management or exercise program within 4 weeks before randomization Subject is able and willing to comply with the study's visit requirement Exclusion Criteria: History of type 1 insulin-dependent diabetes Significant signs and symptoms of uncontrolled hyperglycemia (ie, polyuria, polydypsia, polyphagia), in the opinion of the investigator History of significant weight gain or loss (+/- 5%) during the 4 weeks before randomization Triglycerides ≥ 400 mg/dL (4.5 mmol/L) and/or total cholesterol ≥340 mg/dL (8.7 mmol/L) at screening Currently receiving or received within 60 days prior to screening any anti-diabetic pharmaceutical therapy (eg, insulin) other than metformin and/or sulfonylurea. If receiving metformin or sulfonylurea, doses must be stable for ≥ 60 days. Uncontrolled hypertension defined as diastolic pressure > 95 mmHg and/or systolic > 170 mmHg during screening Hepatic function test (alanine aminotranferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin) results at screening > 2 times the upper limit of normal for the central laboratory White blood cell count < 3000 / μL, absolute neutrophil count (ANC) of < 2500 / μL, or platelet count of < 125,000 / μL at screening Any significant inflammatory, rheumatologic, or systemic autoimmune disease in the opinion of the investigator Evidence of active infection, recent infection, or chronic infection, requiring treatment with anti-infectives, hospitalization or IV antibiotics within 4 weeks prior to randomization Active or latent Mycobacterium tuberculosis infection as defined by known positive PPD or chest x-ray findings and failure to complete treatment with appropriate chemoprophylaxis, or exposure to a person with active tuberculosis within 6 months prior to randomization Existence of non-healing wounds or ulcers Known to be positive for hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) Estimated GFR (eGFR) at screening < 30 mL/min as calculated via the MDRD equation (Modification of Diet in Renal Disease study group) Clinical evidence of current malignancy, with the following exceptions: basal or squamous cell carcinoma of the skin, cervical intraepithelial neoplasia, prostate cancer (if stable localized disease, with life expectancy of > 3 years); or receiving or has received chemotherapy and/or radiation therapy for treatment of a malignancy within 6 months prior to randomization Clinically significant cardiovascular disease (eg, heart failure of New York Heart Association [NYHA] class 3 or 4), hematological abnormality, asthma, or chronic obstructive pulmonary disease (eg, requiring oral or IV steroids), in the opinion of the investigator Receipt of any biologic or immunosuppressive therapy (experimental or commercial), including anakinra (Kineret®) or any tumor necrosis factor (TNF) blocking agents (eg, etanercept and infliximab), or live vaccines, within 3 months of randomization Previously received AMG 108 Subject is evidently pregnant (eg, positive human chorionic gonadotropin [HCG] test), is breast feeding, or is of child-bearing potential and not using adequate contraceptive precautions, as determined by the investigator Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s) Subject has any kind of condition (eg, psychiatric illness) or situation that, in the investigator's opinion, compromises the ability of the subject to give written informed consent, may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 40 mg AMG 108 Q2W<br> | Biological: AMG 108<br>* IL-1 inhibitor, subcutaneous injection given every 2 weeks for the duration of the trial. Doses include 150 mg, 75mg, and 40 mg.<br>|
| Active Comparator: 150 mg AMG 108 Q2W<br> | Biological: AMG 108<br>* IL-1 inhibitor, subcutaneous injection given every 2 weeks for the duration of the trial. Doses include 150 mg, 75mg, and 40 mg.<br>|
| Active Comparator: 75 mg AMG 108 Q2W<br> | Biological: AMG 108<br>* IL-1 inhibitor, subcutaneous injection given every 2 weeks for the duration of the trial. Doses include 150 mg, 75mg, and 40 mg.<br>|
| Placebo Comparator: Placebo Q2W<br> | Biological: Placebo<br>* AMG 108 volume matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HbA1c at week 14 (end of treatment) |  | 14 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes Mellitus, AMG 108, HbA1C, glucose, metformin, sulfonylurea, IL-1 Inhibitor, biologic, subcutaneous injection