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

Johnny Ludvigsson12 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Diabetes Mellitus, Type 1

Interventions

Eligibility

Sex: ALLMin age: 12 YearsMax age: 30 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Informed consent given by patients 2. Type 1 diabetes according to the ADA (American Diabetes Association) classification with \< 6 months diabetes duration 3. Age 12.00-29.99 years at diagnosis of Type 1 diabetes 4. Fasting C-peptide ≥0.12 nmol/L 5. Pos GADA(Antibodies to GAD with molecular mass 65,000) but \< 50 000 random units 6. Females must agree to avoid pregnancy and have a negative urine pregnancy test 7. Patients of childbearing potential must agree to using adequate contraception, until 1 year after the last administration of GAD-Alum. Exclusion Criteria: 1. Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted) 2. Continuous treatment with any inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted) 3. Treatment with any oral or injected anti-diabetic medications other than insulin 4. Treatment with Vitamin D, marketed or not, or unwilling to abstain from such medication during the trial 5. A history of anaemia or significantly abnormal haematology results at screening 6. A history of epilepsy, head trauma or cerebro-vascular accident, or clinical features of continuous motor unit activity in proximal muscles 7. Clinically significant history of acute reaction to vaccines or other drugs in the past 8. 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. 9. Participation in other clinical trials with a new chemical entity within the previous 3 months 10. Inability or unwillingness to comply with the provisions of this protocol 11. A history of alcohol or drug abuse 12. A significant illness other than diabetes within 2 weeks prior to first dosing 13. Known human immunodeficiency virus (HIV) or hepatitis 14. 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) 15. Males or females not willing to use adequate contraception until 1 year after the last GAD-Alum treatment 16. 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 17. Deemed by the investigator not being able to follow instructions and/or follow the study protocol

Outcomes

Primary Outcomes

Number of Subjects With Injection Site Reactions Month 1

Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)

Time frame: Month 1

Number of Subjects With Injection Site Reactions Month 2

Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)

Time frame: Month 2

Number of Subjects With Injection Site Reactions Month 3

Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)

Time frame: Month 3

Number of Subjects With Injection Site Reactions Month 32

Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)

Time frame: Month 32, extension period

Secondary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Baseline to month 15

Mean Change in Fasting C-peptide Value, Month 30

Change from baseline to month 30 in fasting C-peptide value

Time frame: Baseline to month 30

Mean Change in Fasting C-peptide Value, Month 43

Change from baseline to month 43 in fasting C-peptide value

Time frame: Baseline to month 43, extension period

Mean Change in HbA1c, Month 15

Change from baseline to month 15 in HbA1c

Time frame: Baseline to month 15

Mean Change in HbA1c, Month 30

Change from baseline to month 30 in HbA1c

Time frame: Baseline to month 30

Mean Change in HbA1c, Month 43

Change from baseline to month 43 in HbA1c

Time frame: Baseline to month 43, extension period

External Insulin Dose, Baseline

External insulin dose at baseline

Time frame: Baseline

External Insulin Dose, Month 15

External insulin dose at month 15

Time frame: Month 15

External Insulin Dose, Month 30

External insulin dose at month 30

Time frame: Month 30

External Insulin Dose, Month 43

External insulin dose at month 43

Time frame: Month 43, extension period

Mean IDAA1c Values, Baseline

Insulin dose-adjusted HbA1c (IDAA1c)

Time frame: Baseline

Mean IDAA1c Values, Month 15

Insulin dose-adjusted HbA1c (IDAA1c)

Time frame: Month 15

Mean IDAA1c Values, Month 30

Insulin dose-adjusted HbA1c (IDAA1c)

Time frame: Month 30

Mean IDAA1c Values, Month 43

Insulin dose-adjusted HbA1c (IDAA1c)

Time frame: Month 43, extension period

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes