Diabetes Mellitus, Type 1 Immunotherapy Dendritic cells Safety Type 1 diabetes Immunotherapie Dendritische cellen Veiligheid
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.
Sponsors
Leiden Universitu Medical Center
Eligibility
Inclusion criteria
Inclusion criteria: • Age 18-50 years; • Diagnosis of type 1 Diabetes Mellitus 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 and witnessed informed consent.
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; • 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 type 1 Diabetes Mellitus; • 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 ( 200 pmol/L; • Peak insulin C-peptide 64 mmol/ mol. • No positive beta-cell autoantibody or antibodies (eligible autoantibodies: anti IAA, GADA or dIA-2A) • Female patients who are pregnant or breastfeeding;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| a. Primary safety endpoints Occurrence of any of the following safety and feasibility concerns: - hypersensitivity reaction grade ¡Ý 3 to PIpepTolDC product upon intradermal injections - disease exacerbation as defined by ¡Ý 40% decrease of stimulated C-peptide production compared to baseline - 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 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 | — |
Contacts
Public ContactJ.J. Zwaginga
P.O.Box 9600
Outcome results
None listed