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

Phase 2TerminatedNCT02387164

Lund University26 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

Conditions

Diabetes Mellitus, Type 1 Prediabetic State

Interventions

Alum-GADDRUG

Two doses à 20 microgram 30 days apart subcutaneously administrated

Vitamin D3DRUG

2000 Units (IE) (50 microgram) vitamin D3 daily

Eligibility

Sex: ALLMin age: 4 YearsMax age: 18 Years

Medical Language ↔ Plain English

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.

Locations (1)

Clinical Research Center, Pediatric Endocrinology, Jan Waldenströms gata 35, 60:11

Malmö, Sweden

Outcomes

Primary Outcomes

Type 1 Diabetes Month 24

Number of patients diagnosed with type 1 diabetes according to ADA (American Diabetes Association) criteria in each study arm month 24

Time frame: 24 months

Type 1 Diabetes Status Overall

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.

Time frame: Over the entire study period up to 2 years

Secondary Outcomes

Number of Patients Developing Impaired Glucose Metabolism Until Month 18

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.

Time frame: During 18 months follow-up

Number of Patients With Progressive Impaired Glucose Metabolism Until Month 18

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.

Time frame: During 18 months follow-up

Injection Site Reactions Day 1

Number of patients experiencing injection site reactions at day 1

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.