GAD-Alum (Diamyd) Administered Into Lymph Nodes in Combination With Vitamin D in Type 1 Diabetes (DIAGNODE-1)

Study Overview
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Brief Summary
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The objectives of the main study is to: Evaluate the safety of giving GAD-Alum (Glutamic acid decarboxylase) (Diamyd) directly into lymph glands in combination with an oral vitamin D regimen Evaluate how the above mentioned treatments influence the immune system and endogenous insulin secretion. The objective of the sub-study is to: Evaluate safety after a fourth injection with 4 μg GAD-Alum direct into an inguinal lymph gland in 3 adult patients from the main study Evaluate how the above mentioned treatment influences the immune system and endogenous insulin secretion.

Detailed Description
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Eligible patients will be treated with 4 µg GAD-Alum into an inguinal lymph gland at three occasions, with one month intervals in combination with Vitamin D (14 000 IU/week) for 4 months, starting 1 month prior to first GAD-Alum injection. A sub-study will include three adult patients from the main study and evaluate safety after a fourth injection with 4 μg GAD-Alum into an inguinal lymph gland in combination with oral vitamin D intake. The Prolonged Extension Study Period is 12 months and will start 30,5 months after baseline.

Official Title
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Open Label Pilot Trial in Adults With Recent-onset T1D to Evaluate the Safety, Diabetes Status and Immune Response of GAD-antigen (Diamyd®) Therapy Administered Into Lymph Nodes in Combination With an Oral Vitamin D Regimen

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: GAD-Alum
* Drug: Vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent given by patients Type 1 diabetes according to the ADA (American Diabetes Association) classification with < 6 months diabetes duration Age 12.00-29.99 years at diagnosis of Type 1 diabetes Fasting C-peptide ≥0.12 nmol/L Pos GADA(Antibodies to GAD with molecular mass 65,000) but < 50 000 random units Females must agree to avoid pregnancy and have a negative urine pregnancy test Patients of childbearing potential must agree to using adequate contraception, until 1 year after the last administration of GAD-Alum. Exclusion Criteria: Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted) Continuous treatment with any inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted) Treatment with any oral or injected anti-diabetic medications other than insulin Treatment with Vitamin D, marketed or not, or unwilling to abstain from such medication during the trial A history of anaemia or significantly abnormal haematology results at screening A history of epilepsy, head trauma or cerebro-vascular accident, or clinical features of continuous motor unit activity in proximal muscles Clinically significant history of acute reaction to vaccines or other drugs in the past Treatment with any vaccine, including influenza vaccine, within 4 months prior to planned first study drug dose or planned treatment with any vaccine up to 4 months after the last injection with study drug. Participation in other clinical trials with a new chemical entity within the previous 3 months Inability or unwillingness to comply with the provisions of this protocol A history of alcohol or drug abuse A significant illness other than diabetes within 2 weeks prior to first dosing Known human immunodeficiency virus (HIV) or hepatitis Females who are lactating or pregnant (the possibility of pregnancy must be excluded by urine βHCG (beta-human chorionic gonadotropin) on-site within 24 hours prior to the GAD-Alum treatment) Males or females not willing to use adequate contraception until 1 year after the last GAD-Alum treatment Presence of associated serious disease or condition, including active skin infections that preclude subcutaneous injection, which in the opinion of the investigator makes the patient non-eligible for the study Deemed by the investigator not being able to follow instructions and/or follow the study protocol

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 30 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GAD-Alum+Vitamin D<br>GAD-Alum (Diamyd) injected into Lymph Nodes Dosage and interval: One injection of 4 µg Diamyd will be administered into the lymph nodes at three occasions, with one month intervals Vitamin D (Calciferol) in oral solution. Dosage and interval: 2000 IU daily for 120 days | Drug: GAD-Alum<br> <br> * Other names: Diamyd;Drug: Vitamin D<br> <br> * Other names: Calciferol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Injection Site Reactions Month 1 | Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching) | Month 1 | 
| Number of Subjects With Injection Site Reactions Month 2 | Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching) | Month 2 | 
| Number of Subjects With Injection Site Reactions Month 3 | Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching) | Month 3 | 
| Number of Subjects With Injection Site Reactions Month 32 | Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching) | Month 32, extension period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in C-peptide AUC (Area Under the Curve) (Mean 120min) Value, Month 15 | Change from baseline to month 15 in C-peptide AUC (Area Under the Curve) (mean 120min) value AUC (mean 120min) (nmol/L) is the C-peptide AUC during an MMTT (nmol/L*minutes) divided by the duration of the MMTT (minutes) i.e. C-peptide weighted average concentration | Baseline to month 15 at 0, 30, 60, 90, 120 minutes post-dose | 
| Mean Change in C-peptide AUC(Mean 120min) Value, Month 30 | Change from baseline to month 30 in C-peptide AUC(mean 120min) value AUC (mean 120min) (nmol/L) is the C-peptide AUC during an MMTT (nmol/L*minutes) divided by the duration of the MMTT (minutes) i.e. C-peptide weighted average concentration | Baseline to month 30 at 0, 30, 60, 90, 120 minutes post-dose | 
| Mean Change in C-peptide AUC(Mean 120min) Value, Month 43 | Change from baseline to month 43 in C-peptide AUC(mean 120min) value AUC (mean 120min) (nmol/L) is the C-peptide AUC during an MMTT (nmol/L*minutes) divided by the duration of the MMTT (minutes) i.e. C-peptide weighted average concentration | Baseline to month 43, extension period at 0, 30, 60, 90, 120 minutes post-dose | 
| Mean Change in C-peptide 90-minute Value, Month 15 | Change from baseline to month 15 in C-peptide 90-minute value | Baseline to month 15 | 
| Mean Change in C-peptide 90-minute Value, Month 30 | Change from baseline to month 30 in C-peptide 90-minute value | Baseline to month 30 | 
| Mean Change in C-peptide 90-minute Value, Month 43 | Change from baseline to month 43 in C-peptide 90-minute value | Baseline to month 43, extension period | 
| Mean Change in Fasting C-peptide Value, Month 15 | Change from baseline to month 15 in fasting C-peptide value | Baseline to month 15 | 
| Mean Change in Fasting C-peptide Value, Month 30 | Change from baseline to month 30 in fasting C-peptide value | Baseline to month 30 | 
| Mean Change in Fasting C-peptide Value, Month 43 | Change from baseline to month 43 in fasting C-peptide value | Baseline to month 43, extension period | 
| Mean Change in HbA1c, Month 15 | Change from baseline to month 15 in HbA1c | Baseline to month 15 | 
| Mean Change in HbA1c, Month 30 | Change from baseline to month 30 in HbA1c | Baseline to month 30 | 
| Mean Change in HbA1c, Month 43 | Change from baseline to month 43 in HbA1c | Baseline to month 43, extension period | 
| External Insulin Dose, Baseline | External insulin dose at baseline | Baseline | 
| External Insulin Dose, Month 15 | External insulin dose at month 15 | Month 15 | 
| External Insulin Dose, Month 30 | External insulin dose at month 30 | Month 30 | 
| External Insulin Dose, Month 43 | External insulin dose at month 43 | Month 43, extension period | 
| Mean IDAA1c Values, Baseline | Insulin dose-adjusted HbA1c (IDAA1c) | Baseline | 
| Mean IDAA1c Values, Month 15 | Insulin dose-adjusted HbA1c (IDAA1c) | Month 15 | 
| Mean IDAA1c Values, Month 30 | Insulin dose-adjusted HbA1c (IDAA1c) | Month 30 | 
| Mean IDAA1c Values, Month 43 | Insulin dose-adjusted HbA1c (IDAA1c) | Month 43, extension period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diamyd, Diabetes, Juvenile Diabetes, Diabetes Type 1, Type 1 Diabetes, Autoimmune Diabetes, Insulin Dependent Diabetes, Type 1 Diabetes Mellitus, rhGAD65 (Recombinant Human GAD with molecular mass 65,000), GAD65, GAD-Alum, Diabetes Mellitus, Diabetes mellitus Type 1, Glucose Metabolism Disorders, Metabolic Diseases, Vitamin D