a study of the safety and pharmacokinetics of an anti-inflammatory therapeutic antibody (mabp1) in patients with type 2 diabetes

Conditions: Type 2 Diabetes

Summary: the purpose of this study is to determine if t2-18c3, a true human monoclonal antibody that blocks inflammation, is safe to use in patients with type 2 diabetes. the study will also be looking at the ability of t2-18c3 to improve control of blood sugar levels in diabetics by blocking inflammation in the pancreas.

this is a phase i, open label study of the safety and pharmacokinetics of t2-18c3 in patients with t2d. nine patients will receive four biweekly iv infusions of the study drug, t2-18c3, at a dose level of 1.25 mg/kg. these patients will be followed for a total of 90 days to examine safety, pharmacokinetics, and preliminary efficacy.

Eligibility criteria:
inclusion criteria: * american diabetes association (ada) diagnostic criteria for type 2 diabetes (t2d) * hba1c \>7.0% and ≤ 10% * current t2d duration \> 3 months at screening * t2d and other diseases must be stable. stable disease is defined as disease which did not require a change in medication or dosing level on 4 or more consecutive days or 7 days in total within 28 days prior to day 0. * age ≥ 18 and ≤ 70 at screening * bmi ≥ 23 and ≤ 40 kg/m2 * for female patients of child-bearing age, a negative serum pregnancy test. for patients with reproductive potential, a willingness to utilize adequate contraception (oral contraception plus a mechanical barrier) and not become pregnant (or have their partner\[s\] become pregnant) during the study * agrees not to change diet and exercise regimen during the trial * signed and dated ethics committee (ec) approved informed consent before any protocol-specific screening procedures are performed exclusion criteria: * use of the following medications: * daily use of steroids or aspirin ≥ 700 mg per week * immunosuppressive treatment * thiazolidinediones * concomitant treatment with any other therapeutic antibody, or treatment with any biologic agent that blocks the il-1 or tnfα signaling pathway * change in medication for diabetes within 28 days prior to day 0, defined as a change in dosing level on 4 or more consecutive days or 7 days in total * hemoglobin \ 1.5mg/dl, ast/alt \>2 x uln, alkaline phosphatase \>2 x uln * abnormal, untreated t3, t4, thyroglobulin, or tsh levels or history of grave's disease * known hiv antibody, hepatitis b surface antigen and/or hepatitis c antibody * history of malignancy within 5 years prior to study entry other than carcinoma in situ of the cervix, or adequately treated, nonmetastatic squamous or basal cell carcinoma of the skin * history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies * history of tuberculosis, positive ppd test, active atopic disease requiring medication, or asthma * infectious disease: * crp \>30 mg/l, fever, or infection requiring treatment with antibiotics within 3 weeks prior to screening * history of recurrent infection or predisposition to infection * active leg or foot ulcer * immunodeficiency * female patients who are pregnant, planning to become pregnant during the course of the study, or breast-feeding * receipt of a live (attenuated) vaccine within 3 months prior to screening * major surgery within 28 days prior to day 0 * participation in an investigational drug or device trial within 30 days prior to screening