Denosumab for Type 1 Diabetes

NCT06524960 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 23797JDRF Award:3-SRA-2023-1421-M-B
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Type 1 Diabetes

Keywords

Type 1 diabetes, denosumab, HbA1c, beta cell function

Outcome Measures

Primary Outcomes (2)

• Primary safety endpoint

  To evaluate the safety of denosumab as assessed by the occurrence of adverse events (primary safety endpoint). Occurrence of treatment-related adverse events in denosumab group compared to placebo group during the 12 months. Toxicity: Toxicity and adverse events (except hypoglycemia and DKA) will be recorded in the eCRFs using the NCI CTCAE v 5.0 (See Section 7.0 for specific AEs). Hypoglycemia and DKA events will be defined per Section 14.1.1. \- From treatment day through Month 12: All grade toxicities/AEs will be recorded. Safety will be assessed at baseline and at 3, 6, 9 and 12 months.

  up to 12 months

• Primary efficacy endpoint

  To evaluate the efficacy of denosumab in improving beta cell function in T1D subjects as measured by difference of mean area under the curve (AUC) of plasma C-peptide during 2-hr mixed meal tolerance test (MMTT) at baseline and 12 months after initiation of treatment (primary efficacy endpoint). Beta cell function as determined by the change in C-peptide AUC during MMTT in denosumab group will be compared to placebo group at 12 months from baseline. Change in Beta cell function (baseline and at 12 months) \- Mixed meal tolerance test

  up to 12 months

Secondary Outcomes (2)

• Beta cell function

  Up to 6 months

• HbA1c improvement

  up to 12 months

Other Outcomes (2)

• Glucose variability

  up to 12 months

• Insulin sensitivity

  up to 12 months

Study Arms (2)

Denosumab

EXPERIMENTAL

Denosumab 60 mg subcutaneous injection

Drug: Denosumab

Placebo

PLACEBO COMPARATOR

Normal Saline 1.0 ml subcutaneous injection

Other: Placebo

Interventions

Denosumab DRUG

Denosumab is a sterile, preservative-free, clear, colorless to pale yellow solution. Each 1 mL single-dose prefilled syringe of denosumab contains 60 mg denosumab (60 mg/mL solution), 4.7% sorbitol, 17 mM acetate, 0.01% polysorbate 20, Water for Injection (USP), and sodium hydroxide to a pH of 5.2.

Denosumab

Placebo OTHER

Placebo is 1 mL of normal saline drawn up in a commercially available syringe.

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (3)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Fouad Kandeel, MD, PhD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

• Rupangi Vasavada, PhD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arthur Riggs Diabetes & Metabolism Research Institute at City of Hope

CONTACT

1-866-44-ISLET(1-866-444-7538); Islets@coh.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Subjects will be randomized to receive denosumab (Prolia) or normal saline placebo. Study treatment assignment will be blinded to study participants and investigators using a modified double-blind approach described below. The statistician at the primary site and the Research Pharmacist and Study Nurse administering denosumab (Prolia)/placebo at each site will know the treatment assignment and no disclosure of treatment will be allowed.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2024
• First Posted: July 29, 2024
• Study Start: September 3, 2024
• Primary Completion (Estimated): October 11, 2027
• Study Completion (Estimated): October 11, 2027
• Last Updated: July 28, 2025

Record last verified: 2025-07

Locations

US (3)