A Phase 1/2 Prospective, Randomized, Double-blind, Placebo-controlled Multi-center Clinical Trial to Determine the Safety and Efficacy of Denosumab in Improving Beta Cell Function and Glycemic Control Among Patients With Type 1 Diabetes
Type 1 diabetes (T1D) arises from abnormal immune cell-mediated injury to beta cells that make insulin. The injured beta cells can then no longer make the needed amount of insulin to stay healthy. However, in the early stages of T1D, some beta cells are still alive and functioning. Treatment to protect the beta cells against injury at this time could slow the progress of disease. Denosumab is an approved treatment for osteoporosis (a disease that thins and weakens the bones), high blood calcium levels, bone cancer, and other bone problems in patients who have cancer. The research team has found that the bone pathway that denosumab works on to treat these bone conditions also has effects on the health of the beta cells. Lab studies suggest that denosumab may protect and/or increase the number of beta cells and improve how well they work. This study will test whether denosumab is safe and improves beta cell function and blood sugar control in people with early T1D.
• Age: Females 18-50 years; males 21-50 years (minimum age based on skeletal maturity)
• Diagnosis of type 1 diabetes (T1D) based on ADA Criteria:
‣ Hyperglycemia (glycosylated hemoglobin (HbA1c) ≥ 6.5%; OR
⁃ fasting plasma glucose ≥ 126 mg/dl (7.0 mmol/L); OR
⁃ 2-hour plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test; OR
⁃ In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥ 200 mg/dl (11.1 mmol/L)
• Documented history of at least one type 1 diabetes associated autoantibody
‣ GAD specific autoantibodies (GADA);
⁃ Islet-antigen 2 specific autoantibody (IA-2A); and/or
⁃ Zinc Transporter 8 specific autoantibody (ZNT8A)
• Time from T1D diagnosis to screening MMTT must be ≥ 12 months but ≤ 5 years
• Non-fasting C-peptide concentrations of at least 0.2 nmol/L (0.6 ng/ml) at pre-screening and confirmed during a MMTT done at screening visit.
• Serum calcium (corrected for albumin)\* within normal limits per site's local lab
• Agreement by women of childbearing potential (WOCBP) and males of childbearing potential to use a highly effective method of birth control for the course of the study through at least 5 months from the last dose of protocol therapy