Children with HLA risk and persistent islet autoantibody positivity which is associated with a defined risk for type 1 diabetes
Conditions
Interventions
Product Name: Diamyd
Product Code: rhGAD65 formulated in alum (GADalum)
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: No INN proposed, rhGAD65 formulated in alum (GAD-alum)
Other
Sponsors
Helena Elding Larsson
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Children from four (4) to 17,99 years of age. 2. Positive GAD65Ab and at least one additional type 1 diabetes-associated autoantibody (IA-2Ab, ZnT8R/W/Q/AAb or IAA). 3. Written informed consent from the child and the child’s parents or legal acceptable representative(s) according to local regulations. Are the trial subjects under 18? yes Number of subjects for this age range: 80 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Ongoing treatment with immunosuppressant therapy (topical or inhaled steroids are accepted). 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, other than influenza, within one month prior to the first dose of the study drug or planned treatment with vaccine up to two 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 other than diabetes within 2 weeks prior to first dosing. 12. Known human deficiency virus (HIV) or hepatitis. 13. Presence of associated serious disease or condition, including active skin infections that preclude subcutaneous injection, which in the opinion of the investigators makes the patient non-eligible for the study. 14. Diabetes-protective HLA-DQ6-genotype. 15. Females who are lactating or pregnant (for females who have started menstruating the possibility of pregnancy must be excluded by urine ßHCG onsite within 24 hours prior to the study drug administration) 16. Males or females not willing to use adequate contraception, if sexually active, until 1 year after the last Diamyd administration. Adequate contraception is as follows: For females of childbearing potential: a. oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable, or implanted hormonal contraceptives (females) b. intrauterine device (females) c. intrauterine system (for example, progestin-releasing coil) (females) d. vasectomized male (with appropriate postvasectomy documentation of the absence of sperm in the ejaculate) For males of childbearing potential: a. condom (male)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate if Diamyd®, in children treated with relatively high dose vitamin D, may delay or stop the autoimmune process leading to clinical type 1 diabetes in children with ongoing persistent beta cell autoimmunity as indicated by multiple positive islet cell autoantibodies. ;Secondary Objective: The secondary objective is to demonstrate that Diamyd® is safe in children at risk for type 1 diabetes. ;Primary end point(s): The proportion of subjects diagnosed with clinical type 1 diabetes in the Diamyd® treated group, compared to the placebo treated group at five years after the first injection. ;Timepoint(s) of evaluation of this end point: At 5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate safety and the change in metabolic status from normal to impaired glucose metabolism in the group of children with normal glucose metabolism at baseline as well as the progression in metabolic status in the children with impaired glucose metabolism at baseline screening, in the non-diabetic children with multiple islet autoantibodies treated with Diamyd® compared to those treated with placebo. Variables to evaluate safety: • Injection site reactions • Occurrence of adverse events (AEs) • Laboratory measurements (biochemistry and haematology including complete blood count (CBC)), including Calcium and Vitamin D in serum • Urine analysis • Physical examinations, including neurological assessments • Epitope-specific GADA titer, isotypes and subtypes as well as antiidiotypic autoantibodies to GADA Metabolic status: • Change from normal to impaired glucose metabolism, defined as any of a) F-glucose = 6.1 mmol/L b) maximum p-glucose at 30, 60, 90 minutes = 11.1 mmol/L in the OGTT c) 120 min p-glucose = 7.8 mmol/L on OGTT d) HbA1c = 39 mmol/mol. Impaired glucose metabolism has to be confirmed at a second visit. This endpoint will be used in the group of children with normal glucose metabolism at baseline screening • Progression of impaired glucose metabolism from one or several of the above variables to additional signs of reduced glucose metabolism, confirmed at a second visit. This endpoint will be used in the group of children with impaired glucose metabolism at baseline. Exploratory endpoints: • Proportion of subjects diagnosed with clinical type 1 diabetes at 1, 2, 3 and 4 years of follow-up. • Time from baseline visit to clinical type 1 diabetes diagnosis • Change from baseline in the following key metabolic variables at various time points: HbA1c, First phase insulin response and K-value from IvGTT, AUC p-glucose and C-peptide from OGTT, 120 minutes glucose and C-peptide after OGTT, fasting C-pepti | — |
Countries
Sweden
Contacts
Public ContactHelena Elding Larsson
Skåne University Hospital
Outcome results
None listed