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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Diabetes, Hypoglycemia

Intervention / Treatment
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* Drug: BHT-3021
* Drug: BHT-Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>BHT-3021 | Drug: BHT-3021<br>* Evaluation of up to four dose levels will be given in weekly IM injections for 12 weeks.<br>|
| Placebo Comparator: 2<br>BHT-Placebo | Drug: BHT-Placebo<br>* Evaluation of up to four dose levels will be given in weekly IM injections for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint in this study is safety.Safety parameters include: stimulated C-peptide response levels, opthalmologic examination, laboratory assessments, 24-hr urine protein, allergic reactions and adverse events including hypoglycemia. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary endpoints are pharmacodynamic parameters. Parameters include plasmid levels and insulin mRNA levels in blood and urine, Stimulated C-peptide response and Immunological response. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic, Diabetes, Type 1 Diabetes, Type 1 Diabetes Mellitus, autoimmune disease