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Prevention Trial: Immune-tolerance With Alum-GAD (Diamyd) and Vitamin D3 to Children With Multiple Islet Autoantibodies (DiAPREV-IT2)

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ClinicalTrials.gov Identifier: NCT02387164
Recruitment Status : Terminated (The study was interrupted early and terminated when only 26 out of 80 patients were enrolled due to new clinical study results indicating that the current study would not be informative.)
First Posted : March 12, 2015
Results First Posted : October 27, 2020
Last Update Posted : November 17, 2020
Sponsor:
Collaborator:
Region Skane
Information provided by (Responsible Party):
Helena Elding Larsson, Lund University

Tracking Information
First Submitted Date  ICMJE March 5, 2015
First Posted Date  ICMJE March 12, 2015
Results First Submitted Date  ICMJE September 10, 2020
Results First Posted Date  ICMJE October 27, 2020
Last Update Posted Date November 17, 2020
Actual Study Start Date  ICMJE March 9, 2015
Actual Primary Completion Date October 7, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 27, 2020)
  • Type 1 Diabetes Month 24 [ Time Frame: 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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 6, 2015)
Type 1 diabetes [ Time Frame: 5 years ]
Proportion of subjects diagnosed with type 1 diabetes according to ADA criteria in each study arm
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 2, 2020)
  • Number of Patients Developing Impaired Glucose Metabolism Until Month 18 [ Time Frame: 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.
  • Number of Patients With Progressive Impaired Glucose Metabolism Until Month 18 [ Time Frame: 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 Day 1 [ Time Frame: Day 1 ]
    Number of patients experiencing injection site reactions at day 1
  • Injection Site Reactions Month 1 [ Time Frame: Month 1 ]
    Number of patients experiencing injection site reactions at month 1
  • Change From Baseline in GADA Month 1 [ Time Frame: Month 1 ]
    Change from baseline to month 1 in GADA (Glutamic Acid Decarboxylase Antibodies) titers
  • Change From Baseline in GADA Month 12 [ Time Frame: Month 12 ]
    Change from baseline to month 12 in GADA titers
  • Change From Baseline in GADA Month 24 [ Time Frame: Month 24 ]
    Change from baseline to month 24 in GADA titers
Original Secondary Outcome Measures  ICMJE
 (submitted: March 6, 2015)
  • Impaired glucose metabolism [ Time Frame: During 5 year 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.
  • Safety as measured by occurrence of adverse events [ Time Frame: 5 years follow-up ]
    Evaluation of safety of Diamyd and high dose Vitamin D3 in non-diabetic children as measured by occurrence of adverse events, injection site reactions, abnormal laboratory parameters or physical exam.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Prevention Trial: Immune-tolerance With Alum-GAD (Diamyd) and Vitamin D3 to Children With Multiple Islet Autoantibodies
Official Title  ICMJE 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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Diabetes Mellitus, Type 1
  • Prediabetic State
Intervention  ICMJE
  • Drug: Alum-GAD
    Two doses à 20 microgram 30 days apart subcutaneously administrated
    Other Names:
    • Diamyd
    • GAD-Alum
    • Alumformulated GAD
  • Drug: Vitamin D3
    2000 Units (IE) (50 microgram) vitamin D3 daily
    Other Name: Cholecalciferol
Study Arms  ICMJE
  • Experimental: Alum-GAD, 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.
    Interventions:
    • Drug: Alum-GAD
    • Drug: Vitamin D3
  • Placebo Comparator: Placebo, 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
    Intervention: Drug: Vitamin D3
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 14, 2019)
26
Original Estimated Enrollment  ICMJE
 (submitted: March 6, 2015)
80
Actual Study Completion Date  ICMJE October 7, 2019
Actual Primary Completion Date October 7, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02387164
Other Study ID Numbers  ICMJE DiAPREV/2014
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Helena Elding Larsson, Lund University
Study Sponsor  ICMJE Lund University
Collaborators  ICMJE Region Skane
Investigators  ICMJE
Principal Investigator: Helena Elding Larsson, MD, PhD Lund University
PRS Account Lund University
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP