MedDRA version: 21.0 Level: PT Classification code 10066389 Term: Latent autoimmune diabetes in adults System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: rhGAD65-alum
Pharmaceutical Form: Solution for injection
INN or Proposed INN: GAD-alum
Other descriptive name: RHGAD65
Concentration unit: µg/ml microgram(s)/millilitre
Concentration typ
Sponsors
NTNU, Dept of Clinical and Molecular Medicine, Gastrosenteret
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent by the patient. 2. Diagnosis of LADA and diabetes debut within the last 18 months before inclusion 3. Male or female between 30-70 years of age 4. Fasting C-peptide levels = 0.3 nmol/l 5. High anti-GAD titers (>190 U/ml) 6. Patients must be insulin independent at baseline by clinical judgement and C-peptide criteria 7. Antidiabetic medication in the form of metformin is acceptable for inclusion as well as medications not mentioned under exclusion criteria 8. Females must agree to avoid pregnancy and have a negative urine pregnancy test. Patients of childbearing potential must agree to use adequate contraception, until one (1) year after the last administration of GAD-alum Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 1. Current or previous treatment with immunosuppressant therapy (topical or inhaled steroids are accepted) 2. Continuous treatment with anti-inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted) 3. Systemic treatment with glucocorticoids 4. Treatment with any vaccine, including influenza vaccine, within 1 month prior to planned first study drug dose or planned treatment with any vaccine up to 1 month after the last injection with study drug 5. Antidiabetic medication (metformin excepted) 6. Significantly abnormal hematology results at screening 7. A history of epilepsy, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles 8. Clinically significant history of acute reaction to vaccines in the past. 9. Renal disease (as defined by serum creatinine >150 µmol/l) 10. Serious cardiovascular events (myocardial infarction, stroke) within the last year preceding recruitment. 11. Participation in other clinical trials with a new chemical entity within the previous 3 months 12. A history of alcohol or drug abuse 13. Known HIV or hepatitis 14. Presence of associated serious disease or condition, including active skin infections that preclude intralymphatic injection, which in the opinion of the investigator makes the patient non-eligible for the study 15. Other serious chronic disease as judged by investigator. 16. Females who are lactating, are pregnant or intend to become pregnant. 17. Inability or unwillingness to comply with the provisions of this protocol 18. Deemed by the investigator not being able to follow instructions and/or follow the study protocol 19. Treatment with any other supplementation of vitamin D, marketed or not, or unwilling to abstain from such medication during the 120 days daily intake of Divisun (non-investigational medicinal product)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The purpose of the trial is to evaluate the effects of 3 intra-nodal injections of GAD-alum in a population of LADA patients with high GADA titers. The primary objective is to evaluate safety and feasibility of this treatment regimen. The pilot study will be performed in order to support the launch of a larger placebo controlled clinical trial in the LADA population. ;Secondary Objective: Secondary objectives are to test if the treatment induces a strong GAD-specific immune response similar to what has previously been observed in type 1 diabetes patients and to test for indications of preservation of endogenous insulin production.;Primary end point(s): Variables for evaluation of safety and feasibility: 1) Injection site reactions 2) Occurrence of AEs 3) Laboratory measurements (hematology and clinical chemistry) 4) Physical examinations, including neurological assessments 5) anti-GAD65 titer in serum 6) Vital signs (blood pressure) ;Timepoint(s) of evaluation of this end point: 1) Injection site reactions will be evaluated 1 hour post injection vs. before injection. 2) Occurrence of Adverse Events will be evaluated continuously during the study. Status will be summarized at 5 and 12 months after the first injection. 3)-6) Status will be summarized at 5 and 12 months after the first injection. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1)-9) Status will be summarized at 5 and 12 months after the first injection of GAD-alum and compared to status at baseline.;Secondary end point(s): Variables for the evaluation of beta cell insulin secretion capacity and metabolic control: 1) Insulin secretion capacity measured by glucagon- and MMTT (mixed meal tolerance test) stimulated C-peptide. 2) HbA1c. 3) Fasting glucose. 4) Fasting C-peptide 5) Maximum C-peptide during MMTT. Variables for the evaluation of immunological response: 6) Serum concentration of GAD65-specific IgG1, IgG2, IgG3 and IgG4 antibodies for all included patients 7) Supernatant concentrations of IL-1, IL-2, IL-5, IL-13, IL-10, IL-17, IFN-? and TNF secreted during cultivation of PBMCs isolated from all included patients 8) Characterization of PBMCs with FACS using CD3, CD4, CD8, CD45RA, CCR7, CD25, CD127, FOXp3 at baseline 9) Analyses of the proliferation of PBMCs isolated from all included patients during cultivation with vehicle, GAD65 and control antibody. | — |
Countries
Norway, Sweden
Contacts
Public ContactIngrid K Hals
NTNU, Dep of Clinical and Molecular Medicine, Gastrosenteret
Outcome results
None listed