A PHASE I STUDY OF FG-3019 IN SUBJECTS WITH TYPE I OR II DIABETES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The research is a Phase 1 study of the safety, biologic activity and effects of escalating doses of FG-3019 in patients with Type 1 or Type 2 diabetes and microalbuminuria (an early stage of diabetic kidney disease, also known as incipient nephropathy). FG-3019 is a human antibody to a protein known as Connective Tissue Growth Factor (CTGF), present in excess in the glomeruli of subjects with microalbuminuria due to Type 1 or Type 2 diabetes mellitus. The primary objective of this study is to determine the safety, tolerability and biologic activity of the drug FG-3019 in diabetic patients whose kidney disease is manifested by microalbuminuria (incipient nephropathy). The secondary objective is to is to determine whether the drug improves microalbuminuria and/or kidney function by comparing baseline values to post-infusion values. The study will not be powered for the secondary outcomes. Three centers will participate in the study: Los Angeles Biomedical Institute, the Joslin Clinic, and the University of Virginia. Enrollment will be competitive, and 20 subjects will be entered at all 3 centers. After obtaining a written informed consent, up to 20 subjects with microalbuminuria will be enrolled in this study in two groups of ten. The first 10 subjects will receive a low dose of FG-3019. Assuming acceptable tolerability, the second group will receive a higher dose of FG-3019. Subjects will initially undergo screening to ensure eligibility. Subject will actively participate in the study for approximately 12 months, during which time a total of four infusions of the drug FG-3019, given every other week over the course of a six week treatment period, will be administered under continuous monitoring in the Harbor-UCLA GCRC, a facility that is well equipped to manage any kind of emergency that may occur during infusions. The first and last infusions will be given during an overnight admission to the GCRC. The second and third admission will involve a 6-hour period of observation after the infusion is completed. Blood and urine samples will be collected before and after each infusion to evaluate the effects of FG-3019. The subject will also come in for frequent visits during the whole length of the study to determine if he/she is experiencing any adverse effects as a result of the infusion and to assess any change in the functioning of the kidneys by measurements from urine and blood samples. The study procedure will be implemented only after obtaining written informed consent, signed and dated by the subject or the subject's legally authorized representative at the time of consent. A copy of the signed informed consent will be given to the person signing the form. Medical information obtained as part of this study will be confidential and will not be disclosed to third parties except on written request by the subject that medical information be given to his/her personal physician. The subjects enrolled in the study will be compensated financially to reimburse for transportation and to compensate for the time devoted to participate in study procedures. There are certain risks to the patients enrolled in the study. These include sensitivity to the drug, and infusion-related events like fever, chills, and rigors. Other signs and symptoms may include headache, nausea, dizziness or hypotension. The chances of these risks are thought to be small. Twenty-one subjects with lung scarring have received single doses of FG-3019 without experiencing serious side-effects. If FG-3019 is safe and effective, the subject may potentially benefit, albeit probably only transiently, by improvement in microalbuminuria or kidney function. However the major benefits of this study will be to the society at large, since the prevalence of diabetes is high and the incidence is increasing worldwide. This drug, if found safe and possibly effective in the human subjects enrolled in the study, could represent a first step in evaluating the efficacy of a first-in-class agent for the treatment of diabetic kidney disease.