Effects of Recombinant Human Glutamic Acid Decarboxylase on the Progression of Type 1 Diabetes in New Onset Subjects

Study Overview
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Brief Summary
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The purpose of this study is to determine whether treatment with multiple injections of GAD-Alum will preserve the body's own (endogenous) insulin production in patients who have been recently diagnosed with type 1 diabetes mellitus (T1DM).

Detailed Description
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Type 1 diabetes (T1D) is an autoimmune disease. This means that the immune system (the part of the body which helps fight infections) mistakenly attacks and destroys the cells that produce insulin (islet cells found in the pancreas called islet cells). As these cells are destroyed, the body's ability to produce insulin decreases. Glutamic acid decarboxylase (GAD) is one of the major autoantigens (a protein that the immune system is reacting to) involved in the autoimmune process underlying T1DM. GAD-Alum is Recombinant human (rhGAD65) and is used as an antigen-specific immune modulator. Previous studies have shown that it may slow or prevent autoimmune destruction of pancreatic islet cells by introducing immune tolerance. By administering excess autoantigen, the body may stop its attack on its own cells that produce insulin. If the immune system's attack can be halted in a patient with recent onset T1DM, than residual insulin secretion may be maintained. This may be beneficial in decreasing acute and long-term diabetic complications as well as improving glucose control.

Official Title
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Effects of Recombinant Human Glutamic Acid Decarboxylase (rhGAD65) Formulated in Alum (GAD-alum) on the Progression of Type 1 Diabetes in New Onset Subjects

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: GAD-Alum
* Drug: GAD-Alum and Aluminum hydroxide
* Drug: Aluminum hydroxide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 3 to 45 years - Insulin dependent type 1-diabetes mellitus diagnosed within the previous 3 months Stimulated C-peptide levels greater than or equal to 0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) conducted 3 weeks from diagnosis of diabetes Presence of GAD65 antibodies At least one month from last immunization Willing to comply with intensive diabetes management If participant is a woman with reproductive potential, she must be willing to avoid pregnancy and have a negative pregnancy test Willing to forgo routine clinical immunizations during the first 100 days after initial study drug administration Exclusion Criteria: Immunodeficiency or clinically significant chronic lymphopenia Active infection Positive PPD test result Pregnant or lactating or anticipating becoming pregnant for 24 months following first injection Ongoing use of medications known to influence glucose tolerance Require use of systemic immunosuppressant(s) Serologic evidence of current or past HIV, Hep B, or Hep C infection History of malignancies Ongoing use of non-insulin pharmaceuticals to affect glycemic control Participation in another clinical trial with a new chemical entity within the past 3 months Complicating medical issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk including neurological, or clinically significant blood count abnormalities (such as lymphopenia, leukopenia, or thrombocytopenia) History of epilepsy, head trauma or cerebrovascular accident or clinical History of alcohol or drug abuse

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 45 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>3 injections of GAD-Alum vaccine | Drug: GAD-Alum<br>* Participants will receive 3 injections of 20 micrograms GAD-Alum subcutaneously. The first two injections are given 4 weeks apart and the second and third are given 8 weeks apart.<br>* Other names: Diamyd;|
| Experimental: 2<br>2 injections of GAD-Alum vaccine and one injection with Aluminum hydroxide alone | Drug: GAD-Alum and Aluminum hydroxide<br>* Participants will receive 3 injections subcutaneously. The first two will contain 20 micrograms GAD-Alum vaccine and are given 4 weeks apart. The third injection will be Aluminum hydroxide alone and will be given 8 weeks after the second injection.<br>* Other names: Diamyd;|
| Placebo Comparator: 3<br>3 injections of Aluminum hydroxide alone | Drug: Aluminum hydroxide<br>* Participants will receive 3 injections of Aluminum hydroxide alone, subcutaneously. The first two injections are given 4 weeks apart and the second and third are given 8 weeks apart.<br>* Other names: Alhydrogel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Outcome is the Area Under the Stimulated C-peptide Curve (AUC) at the One Year Visit | The primary outcome is the area under the stimulated C-peptide curve (AUC) based on data collected at time 0 to 2 hours of a 4-hour mixed meal glucose tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30 60, 90, and 120 minutes. | Based on mixed meal tolerance test (MMTT) conducted at the one year visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immune tolerance, immunotherapy, antigen-specific tolerance, vaccine induced tolerance, Beta-cell function, T-cells, DPT-1, treatment of type 1 diabetes, new onset type 1 diabetes, juvenile diabetes, T1D, diabetes mellitus, Type 1 diabetes TrialNet, TrialNet