diabetes type 1 diabetes
Conditions
Interventions
Two intradermal injections of PIpepTolDCs (5x 10e6, 10x 10e6 or 20 x 10e6/
injection in 3 patients each) with a 28-day interval.
Patienten worden behandeld met 2 series van intradermale injecties me
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Age 18-45 years; • Diagnosis of T1D at least 18 months dated from the first insulin injection • Adequate self-assessment of blood glucose values, and recording of glucose values and administered insuline doses as deemed sufficient by the patient*s physician • Stable glycemic control according to the patient*s physician • Possession of *0401 allele at the HLA-DRB1 gene locus; • Written informed consent. Pregnancies during the study must be prevented both by female participant and in case of male participants by them or their partners.
Exclusion criteria
Exclusion criteria: • Use of immunosuppressive or immunomodulatory therapies, including systemic steroids within 1 month prior to enrolment and/or prior monoclonal antibody therapy of any type given for any indication at any time; • Use of beta-cell stimulants (e.g. sulphonylureas), glucagon-like peptide-1 agonists, dipeptidyl peptidase-IV inhibitors, insulin sensitizers (e.g. metformin, thiazolidinediones) • Immunisation with live or killed vaccines or allergic desensitization procedures less than 1 month prior to enrolment; • History of disease associated with autoimmunity or inflammatory disorders other than T1D; • History of malignancy; • Male or female patients who are fertile and are unwilling to use adequate contraception at least 3 months prior to the first administration of PIpepTolDCs until at least 60 days following the last administration of PIpepTolDCs; • Recent ( 64 mmol/ mol. • Lack of beta-cell autoantibodies (eligible autoantibodies: GADA or dIA-2A) • Low vitamin D25 (OH) (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| a. Primary safety endpoints Occurrence of any of the following safety and feasibility concerns: - hypersensitivity reaction grade >= 3 to PIpepTolDC product upon intradermal injections - any infectious complications requiring systemic medical treatment - diagnosis of any new disease associated with autoimmunity - diagnosis of new malignancy - any other serious adverse event b. Primary feasibility endpoints - failure to complete a successful leukapheresis procedure - failure to isolate sufficient numbers of mononuclear cells by leukapheresis for PIpepTolDC production - failure to generate the required dose of PIpepTolDCs - any event that prevents the protocol or follow up to be executed as planned. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints - Improved or decreased stimulated C-peptide production compared to baseline at 12 and 24 weeks - Change in the level or quality of T-cell specific immune responses at 4, 8, 12, and 24 weeks versus baseline. Long term follow up (amendment): - General medical history taking at least one time >1 year after vaccination and if consented by the patient yearly thereafter . - Assessment of remaining changes in the level or quality of T-cell specific immune responses at least one time > 1 year after vaccination and if consented by the patient yearly thereafter versus baseline as defined by: o Change in responsiveness to proinsulin peptide or protein from IFNg- into IL-10-producing as detected by ELISPOT; o Disappearance of T cell responsiveness to autoantigens (GAD, IA-2), as determined by lymphocyte stimulation test (LST); o Disappearance of autoreactive CD8+ T cells as determined by Q-DOT. | — |
Countries
Netherlands
Outcome results
None listed