Clinical trial NCT02352974: GAD-Alum (Diamyd) Administered Into Lymph Nodes in Combination With Vitamin D in Type 1 Diabetes (DIAGNODE-1)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 1
Keywords: 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
Lead sponsor: Linkoeping University
Sponsor class: OTHER_GOV
Collaborators: name: Swedish Child Diabetes Foundation
name: Ostergotland County Council, Sweden
name: Diamyd Medical AB
First posted: 2015-02-02
Enrollment: 12
Sex: ALL
Minimum age (years): 12
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Subjects With Injection Site Reactions Month 1
timeFrame: Month 1
measure: Number of Subjects With Injection Site Reactions Month 2
timeFrame: Month 2
measure: Number of Subjects With Injection Site Reactions Month 3
timeFrame: Month 3
measure: Number of Subjects With Injection Site Reactions Month 32
timeFrame: Month 32, extension period
Secondary outcomes:
measure: Mean Change in C-peptide AUC (Area Under the Curve) (Mean 120min) Value, Month 15
timeFrame: Baseline to month 15 at 0, 30, 60, 90, 120 minutes post-dose
measure: Mean Change in C-peptide AUC(Mean 120min) Value, Month 30
timeFrame: Baseline to month 30 at 0, 30, 60, 90, 120 minutes post-dose
measure: Mean Change in C-peptide AUC(Mean 120min) Value, Month 43
timeFrame: Baseline to month 43, extension period at 0, 30, 60, 90, 120 minutes post-dose
measure: Mean Change in C-peptide 90-minute Value, Month 15
timeFrame: Baseline to month 15
measure: Mean Change in C-peptide 90-minute Value, Month 30
timeFrame: Baseline to month 30
measure: Mean Change in C-peptide 90-minute Value, Month 43
timeFrame: Baseline to month 43, extension period
measure: Mean Change in Fasting C-peptide Value, Month 15
timeFrame: Baseline to month 15
measure: Mean Change in Fasting C-peptide Value, Month 30
timeFrame: Baseline to month 30
measure: Mean Change in Fasting C-peptide Value, Month 43
timeFrame: Baseline to month 43, extension period
measure: Mean Change in HbA1c, Month 15
timeFrame: Baseline to month 15
measure: Mean Change in HbA1c, Month 30
timeFrame: Baseline to month 30
measure: Mean Change in HbA1c, Month 43
timeFrame: Baseline to month 43, extension period
measure: External Insulin Dose, Baseline
timeFrame: Baseline
measure: External Insulin Dose, Month 15
timeFrame: Month 15
measure: External Insulin Dose, Month 30
timeFrame: Month 30
measure: External Insulin Dose, Month 43
timeFrame: Month 43, extension period
measure: Mean IDAA1c Values, Baseline
timeFrame: Baseline
measure: Mean IDAA1c Values, Month 15
timeFrame: Month 15
measure: Mean IDAA1c Values, Month 30
timeFrame: Month 30
measure: Mean IDAA1c Values, Month 43
timeFrame: Month 43, extension period
Other outcomes:
Locations:
city: Linköping
country: Sweden
facility: Linköping University
Study officials:
affiliation: Linkoeping University
name: Johnny Ludvigsson, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Casas R, Dietrich F, Barcenilla H, Tavira B, Wahlberg J, Achenbach P, Ludvigsson J. Glutamic Acid Decarboxylase Injection Into Lymph Nodes: Beta Cell Function and Immune Responses in Recent Onset Type 1 Diabetes Patients. Front Immunol. 2020 Oct 9;11:564921. doi: 10.3389/fimmu.2020.564921. eCollection 2020.
citation: Tavira B, Barcenilla H, Wahlberg J, Achenbach P, Ludvigsson J, Casas R. Intralymphatic Glutamic Acid Decarboxylase-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients: A Pilot Clinical Trial in Type 1 Diabetes. J Diabetes Res. 2018 May 24;2018:9391845. doi: 10.1155/2018/9391845. eCollection 2018.