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

Diabetes Mellitus, Type 1 Clinical Trial

— DiAPREV-IT2  

Official title:

Double-blind, Investigator-initiated Study to Determine the Effect of Alum-GAD (Diamyd) in Combination With Vitamin D3 on the Progression to Type 1 Diabetes in Children With Multiple Islet Autoantibodies

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02387164
• Other study ID #: DiAPREV/2014
• Status: Terminated
• Phase: Phase 2
• Start date: March 9, 2015
• Est. completion date: October 7, 2019

Study information

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

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: October 7, 2019
• Est. primary completion date: October 7, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Prediabetic State

Intervention

Drug:
• Alum-GAD
Two doses à 20 microgram 30 days apart subcutaneously administrated
• Vitamin D3
2000 Units (IE) (50 microgram) vitamin D3 daily

Locations

Country	Name	City	State
Sweden	Clinical Research Center, Pediatric Endocrinology, Jan Waldenströms gata 35, 60:11	Malmö

Sponsors (2)

Lead Sponsor	Collaborator
Lund University	Region Skane

Country where clinical trial is conducted

Sweden, 

References & Publications (3)

Andersson C, Carlsson A, Cilio C, Cedervall E, Ivarsson SA, Jonsdottir B, Jönsson B, Larsson K, Neiderud J, Lernmark A, Elding Larsson H; DiAPREV-IT Study Group. Glucose tolerance and beta-cell function in islet autoantibody-positive children recruited to a secondary prevention study. Pediatr Diabetes. 2013 Aug;14(5):341-9. doi: 10.1111/pedi.12023. Epub 2013 Mar 8. — View Citation

Elding Larsson H, Larsson C, Lernmark Å; DiAPREV-IT study group. Baseline heterogeneity in glucose metabolism marks the risk for type 1 diabetes and complicates secondary prevention. Acta Diabetol. 2015 Jun;52(3):473-81. doi: 10.1007/s00592-014-0680-1. Epub 2014 Nov 8. — View Citation

Ludvigsson J, Krisky D, Casas R, Battelino T, Castaño L, Greening J, Kordonouri O, Otonkoski T, Pozzilli P, Robert JJ, Veeze HJ, Palmer J, Samuelsson U, Elding Larsson H, Åman J, Kärdell G, Neiderud Helsingborg J, Lundström G, Albinsson E, Carlsson A, Nordvall M, Fors H, Arvidsson CG, Edvardson S, Hanås R, Larsson K, Rathsman B, Forsgren H, Desaix H, Forsander G, Nilsson NÖ, Åkesson CG, Keskinen P, Veijola R, Talvitie T, Raile K, Kapellen T, Burger W, Neu A, Engelsberger I, Heidtmann B, Bechtold S, Leslie D, Chiarelli F, Cicognani A, Chiumello G, Cerutti F, Zuccotti GV, Gomez Gila A, Rica I, Barrio R, Clemente M, López Garcia MJ, Rodriguez M, Gonzalez I, Lopez JP, Oyarzabal M, Reeser HM, Nuboer R, Stouthart P, Bratina N, Bratanic N, de Kerdanet M, Weill J, Ser N, Barat P, Bertrand AM, Carel JC, Reynaud R, Coutant R, Baron S. GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus. N Engl J Med. 2012 Feb 2;366(5):433-42. doi: 10.1056/NEJMoa1107096. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	24 months
Primary	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.	Over the entire study period up to 2 years
Secondary	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.	During 18 months follow-up
Secondary	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.	During 18 months follow-up
Secondary	Injection Site Reactions Day 1	Number of patients experiencing injection site reactions at day 1	Day 1
Secondary	Injection Site Reactions Month 1	Number of patients experiencing injection site reactions at month 1	Month 1
Secondary	Change From Baseline in GADA Month 1	Change from baseline to month 1 in GADA (Glutamic Acid Decarboxylase Antibodies) titers	Month 1
Secondary	Change From Baseline in GADA Month 12	Change from baseline to month 12 in GADA titers	Month 12
Secondary	Change From Baseline in GADA Month 24	Change from baseline to month 24 in GADA titers	Month 24

External Links

•   Link to the description of the first DiAPREV-IT study, that have included 50 children and is still ongoing