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

NCT02352974 | Completed Phase 1 Results

• 1 other identifier: DIAGNODE-1
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (20)

• Mean Change in C-peptide AUC (Area Under the Curve) (Mean 120min) Value, Month 15

  Baseline to month 15 at 0, 30, 60, 90, 120 minutes post-dose

• Mean Change in C-peptide AUC(Mean 120min) Value, Month 30

  Baseline to month 30 at 0, 30, 60, 90, 120 minutes post-dose

• Mean Change in C-peptide AUC(Mean 120min) Value, Month 43

  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

  Baseline to month 15

• Mean Change in C-peptide 90-minute Value, Month 30

  Baseline to month 30

Study Arms (1)

GAD-Alum+Vitamin D

EXPERIMENTAL

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; Drug: Vitamin D

Interventions

GAD-Alum DRUG

Also known as: Diamyd

GAD-Alum+Vitamin D

Vitamin D DRUG

Also known as: Calciferol

GAD-Alum+Vitamin D

Eligibility Criteria

• Age: 12 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Johnny Ludvigsson: lead
• Swedish Child Diabetes Foundation: collaborator
• Ostergotland County Council, Sweden: collaborator
• Diamyd Medical AB: collaborator

Study Sites (1)

Linköping University

Linköping, Sweden

Location

Related Publications (2)

• 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.

  PMID: 33162978 DERIVED

• 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.

  PMID: 30009185 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases

Interventions

Vitamin D; Cholecalciferol

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholestenes; Cholestanes; Sterols; Membrane Lipids; Lipids

Results Point of Contact

• Title: Åsa Carlsheimer
• Organization: 4Pharma AB

asa.carlsheimer@4pharma.com

+4672244516

Study Officials

• Johnny Ludvigsson, Professor

  Linkoeping University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, Professor

Study Record Dates

• First Submitted: December 9, 2014
• First Posted: February 2, 2015
• Study Start: January 1, 2015
• Primary Completion: October 1, 2019
• Study Completion: October 1, 2019
• Last Updated: April 27, 2020
• Results First Posted: April 27, 2020

Record last verified: 2020-04

Locations

SE (1)