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

Diabetes Mellitus, Type 1 Clinical Trial

— DIAGNODE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02352974
• Other study ID #: DIAGNODE-1
• Status: Completed
• Phase: Phase 1
• Start date: January 2015
• Est. completion date: October 2019

Study information

• Verified date: April 2020
• Source: Linkoeping University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: October 2019
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 30 Years

Eligibility

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 ßHCG (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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Drug:
• GAD-Alum

• Vitamin D

Locations

Country	Name	City	State
Sweden	Linköping University	Linköping

Sponsors (4)

Lead Sponsor	Collaborator
Johnny Ludvigsson	Diamyd Medical AB, Ostergotland County Council, Sweden, Swedish Child Diabetes Foundation

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Injection Site Reactions Month 1	Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)	Month 1
Primary	Number of Subjects With Injection Site Reactions Month 2	Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)	Month 2
Primary	Number of Subjects With Injection Site Reactions Month 3	Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)	Month 3
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Mean Change in Fasting C-peptide Value, Month 15	Change from baseline to month 15 in fasting C-peptide value	Baseline to month 15
Secondary	Mean Change in Fasting C-peptide Value, Month 30	Change from baseline to month 30 in fasting C-peptide value	Baseline to month 30
Secondary	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
Secondary	Mean Change in HbA1c, Month 15	Change from baseline to month 15 in HbA1c	Baseline to month 15
Secondary	Mean Change in HbA1c, Month 30	Change from baseline to month 30 in HbA1c	Baseline to month 30
Secondary	Mean Change in HbA1c, Month 43	Change from baseline to month 43 in HbA1c	Baseline to month 43, extension period
Secondary	External Insulin Dose, Baseline	External insulin dose at baseline	Baseline
Secondary	External Insulin Dose, Month 15	External insulin dose at month 15	Month 15
Secondary	External Insulin Dose, Month 30	External insulin dose at month 30	Month 30
Secondary	External Insulin Dose, Month 43	External insulin dose at month 43	Month 43, extension period
Secondary	Mean IDAA1c Values, Baseline	Insulin dose-adjusted HbA1c (IDAA1c)	Baseline
Secondary	Mean IDAA1c Values, Month 15	Insulin dose-adjusted HbA1c (IDAA1c)	Month 15
Secondary	Mean IDAA1c Values, Month 30	Insulin dose-adjusted HbA1c (IDAA1c)	Month 30
Secondary	Mean IDAA1c Values, Month 43	Insulin dose-adjusted HbA1c (IDAA1c)	Month 43, extension period