Prevention Trial: Immune-tolerance With Alum-GAD (Diamyd) and Vitamin D3 to Children With Multiple Islet Autoantibodies

Phase 2

Terminated

• Conditions: Prediabetic State; Diabetes Mellitus, Type 1
• Interventions: Drug: Alum-GAD; Drug: Vitamin D3

• Registration Number: NCT02387164
• Lead Sponsor: Lund University

Brief Summary

The purpose of this study is to evaluate if immune-tolerance with Alum-formulated GAD (Diamyd), in combination with high dose Vitamin D3, may delay or stop the autoimmune process leading to clinical type 1 diabetes in non-diabetic children with ongoing beta-cell autoimmunity as indicated by positive islet autoantibodies.

Detailed Description

The primary objective of this study is to evaluate if immune-tolerance with Alum-formulated GAD (Diamyd), combined with high dose Vitamin D3, may delay or stop the autoimmune process leading to clinical type 1 diabetes (diagnosed according to American Diabetes Association criteria) in non-diabetic 4-17.99 year old children with ongoing beta-cell autoimmunity as indicated by positive islet autoantibodies.

The secondary objective is to demonstrate that treatment with Diamyd is safe in children at risk for type 1 diabetes.

The children will be followed for 5 years in the study. Primary endpoint is proportion of subjects diagnosed with type 1 diabetes in each treatment arm. Secondary endpoints are 1) safety, 2) change in metabolic status from normal to impaired glucose metabolism in the group of children with normal glucose metabolism at baseline screening.

Study Timeline

• Study First Submitted: 2015-03-05
• Study First Submitted QC: 2015-03-06
• Study Start: 2015-03-09
• Study First Posted: 2015-03-12
• Primary Completion: 2019-10-07
• Study Completion: 2019-10-07
• Results First Submitted: 2020-09-10
• Status Verified: 2020-10
• Results First Submitted QC: 2020-10-02
• Results First Posted: 2020-10-27
• Last Update Submitted: 2020-10-27
• Last Update Posted: 2020-11-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

• Children 4-17.99 years of age with positive autoantibodies to glutamate decarboxylase (GADA) and at least one additional type 1 diabetes associated autoantibody (to insulinoma associated protein 2 (IA-2A), Zinktransporter 8 (ZnT8R/Q/WA) or insulin (IAA)).
• Written informed consent from the child and the childs legal representative(s).

Exclusion Criteria

1. Ongoing treatment with immunosuppressant therapy.
2. Diabetes.
3. Treatment with any oral or injected anti-diabetic medications
4. Significantly abnormal hematology results at screening.
5. Clinically significant history of acute reaction to vaccines or other drugs
6. Treatment with any vaccine within one month prior to the first dose of the study drug or planned treatment with vaccine up to three months after the last injection with the study drug.
7. A history of epilepsy, serious head trauma or cerebrovascular accident, or Clinical features of continuous motor unit activity in proximal muscles
8. Participation in other Clinical trials with a new chemical entity within the previous 3 months.
9. History of hypercalcemia.
10. Unwilling to abstain from other medication with Vitamin D during the study period.
11. Significant illness within 2 weeks prior to first dosing.
12. Known Human Immuno Deficiency Virus infection or hepatitis.
13. Presence of associated serious disease or condition.
14. Diabetes-protective Human Leucocyte Antigen (HLA) DQ6.
15. Females who are lactating or pregnant.
16. Males or females not willing to use adequate contraception, if sexually active, until 1 year after the last Diamyd administration.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Alum-GAD, Vitamin D3	Alum-GAD	Two doses à 20 microgram of subcutaneous alum-GAD (Diamyd), 30 Days apart. Vitamin D 2000 U/Daily with start 30 days before the first injection of Diamyd. Vitamin D treatment will continue throughout the whole study period of 5 years.
Alum-GAD, Vitamin D3	Vitamin D3	Two doses à 20 microgram of subcutaneous alum-GAD (Diamyd), 30 Days apart. Vitamin D 2000 U/Daily with start 30 days before the first injection of Diamyd. Vitamin D treatment will continue throughout the whole study period of 5 years.
Placebo, Vitamin D3	Vitamin D3	Two doses of subcutaneous placebo, 30 Days apart. Vitamin D 2000 U/Daily with start 30 days before the first injection of Diamyd. Vitamin D treatment will continue throughout the whole study period of 5 years

Primary Outcome Measures

Name	Time	Method
Type 1 Diabetes Month 24	24 months	Number of patients diagnosed with type 1 diabetes according to ADA (American Diabetes Association) criteria in each study arm month 24
Type 1 Diabetes Status Overall	Over the entire study period up to 2 years	Number of patients diagnosed with type 1 diabetes according to ADA (American Diabetes Association) criteria in each study arm overall. Including one patient diagnosed shortly after the month 24 visit.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in GADA Month 1	Month 1	Change from baseline to month 1 in GADA (Glutamic Acid Decarboxylase Antibodies) titers
Change From Baseline in GADA Month 12	Month 12	Change from baseline to month 12 in GADA titers
Number of Patients Developing Impaired Glucose Metabolism Until Month 18	During 18 months follow-up	Change in metabolic status from normal to impaired glucose metabolism during follow-up in the group of children with normal glucose metabolism at baseline screening.; Impaired glucose metabolism is defined as a) fasting plasma glucose 6.1 mmol/L or more, b) maximum plasma glucose 30, 60, 90 min during oral glucose tolerance test (OGTT) 11.1 mmol/L or more, c) 120 min plasma glucose on OGTT 7.8 mmol/L or more, d) HbA1c 39 mmol/L or more.
Injection Site Reactions Day 1	Day 1	Number of patients experiencing injection site reactions at day 1
Number of Patients With Progressive Impaired Glucose Metabolism Until Month 18	During 18 months follow-up	Number of patients who have progression from already impaired glucose metabolism from one or several criteria to additional signs of reduced glucose metabolism (within children with impaired glucose metabolism at screening).; Impaired glucose metabolism is defined as a) fasting plasma glucose 6.1 mmol/L or more, b) maximum plasma glucose 30, 60, 90 min during oral glucose tolerance test (OGTT) 11.1 mmol/L or more, c) 120 min plasma glucose on OGTT 7.8 mmol/L or more, d) HbA1c 39 mmol/L or more.
Injection Site Reactions Month 1	Month 1	Number of patients experiencing injection site reactions at month 1
Change From Baseline in GADA Month 24	Month 24	Change from baseline to month 24 in GADA titers

Trial Locations

Locations (1)

Clinical Research Center, Pediatric Endocrinology, Jan Waldenströms gata 35, 60:11; 🇸🇪 Malmö, Sweden