Denosumab for Type 1 Diabetes

Main Inclusion Criteria

• 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

Main Exclusion Criteria

• History of delayed puberty unless there is radiologic evidence of skeletal maturity

• Use of other investigational agents within 3 months of enrollment

• Vitamin D3 deficiency (< 30 ng/ml)

• History of anorexia and/or eating disorder

• BMI > 32 kg/m2

• HbA1c > 9.5%

• Severe hypoglycemia or diabetic ketoacidosis (DKA) within 3 months prior to screening. Subjects who had such episodes within 3-6 months prior to screening, must have written clearance from their treating physician.

• Use of any of the diabetes medications other than insulin within 3 months of enrollment (e.g., metformin, sulfonylurea, GLP-1 agonists, DPP4 inhibitors, Symlin, SGLT2-inhibitors, amylin)

• Treatment with any of the following drugs in past year: immunosuppressants, anticonvulsant therapy, adrenal or anabolic steroids, calcitonin, selective estrogen receptor modulator, sodium fluoride (other than dental treatment), teriparatide, abaloparatide, strontium or aromatase inhibitors; any history of bisphosphonate treatment.

• Bone fractures (excluding skull, facial bones, metacarpals, fingers, toes and spontaneous fractures associated with severe trauma) within the past 12 months

• Disorders associated with altered skeletal structure or function (Paget's disease, chronic liver disease (liver enzymes > twice the upper limit of normal), malignancy, hypoparathyroidism or hyperparathyroidism, acromegaly, Cushing's syndrome, hypopituitarism, chronic obstructive pulmonary disease, alcohol intake > 3 units/day)

• Significant dental/oral disease, including prior history or current evidence of osteonecrosis/osteomyelitis of the jaw, active dental or jaw condition requiring oral surgery, non-healed dental/oral surgery, or planned invasive dental procedures for the course of the study

• Pregnancy or actively breastfeeding (within 6 months prior to screening), or planning to become pregnant with 5 months after last dose of protocol therapy