Phase 1 Study of BHT-3021 in Subjects With Type 1 Diabetes Mellitus

A Randomized, Blinded, Placebo Controlled, Safety and Pharmacodynamic Study of BHT-3021 With Open Label Cross-Over in Subjects With Type I Diabetes Mellitus

The purpose of this study is to determine the safety of BHT-3021 injections given weekly for 12 weeks and to evaluate the effect of BHT-3021 on antibody and immune (T cell) responses to autoantigens (e.g. insulin). Changes in pancreatic beta cell function, insulin requirements and blood glucose levels will also be evaluated.

Type 1 diabetes results from an attack by the body's own immune system on the insulin producing cells in the pancreas. Around 80% of diagnosed patients have detectable antibodies to islet cell self-proteins including, insulin IA-2 and glutamic acid decarboxylase. The drug, BHT-3021 is being studied because an agent that stops autoimmune damage could offer patients benefit.

Study Description: A Randomized, Blinded, Placebo Controlled, Safety and Pharmacodynamic Study of BHT-3021 with Open Label Cross-Over in Subjects with Type I Diabetes Mellitus that will enroll up to 72 subjects in this trial. Subjects will be randomized to BHT-3021 or BHT-placebo in a 2:1 ratio.

The duration of the study is approximately 25 to 37 months depending on treatment assignment: 4 week Screening Period; 12 month Blinded Treatment and Evaluation Period; 12 month Cross-over Treatment and Evaluation Period (BHT-placebo subjects only); 12 month Long Term Follow-Up period.

Inclusion Criteria

• Diagnosis of Type 1a Diabetes Mellitus based on ADA Criteria
• ≤5 years since T1D was diagnosed
• ≥ 18 years of age
• ≤ 40 years of age at the time of diagnosis of Type 1a diabetes
• Presence of antibodies to at least one of the following antigens:

insulin, GAD-65, or IA-2

• Detectable fasting C-peptide level
• C-peptide increase during screening mixed meal tolerance test with a minimal stimulated value of ≥ 0.2 pmol/mL
• Presence of antibodies to at least one of the following antigens: insulin, GAD-65, or IA-2. If insulin antibody positive only, determination must be within 2 weeks of insulin initiation

Exclusion Criteria:

• BMI > 30 kg/m2
• Unstable blood sugar control defined as one or more episodes of severe hypoglycemia (defined as hypoglycemia that required the assistance of another person) within the last 30 days
• Current use of inhalable insulin
• Previous immunotherapy for T1D
• Administration of an experimental agent for T1D at any time or use of an experimental device for T1D within 30 days prior to screening, unless approved by the medical monitor
• History of any organ transplant, including islet cell transplant