No registrations found.
ID
Source
Brief title
Health condition
Diabetes Mellitus, Type 1
Immunotherapy
Dendritic cells
Safety
Type 1 diabetes
Immunotherapie
Dendritische cellen
Veiligheid
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 outcome
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
Study objective
Diabetes Mellitus type 1 is an autoimmune disease that cannot be cured. Complications due to insufficient regulation of blood glucose by exogenous insulin reduce life expectancy and quality of life. Proinsuline-loaded Tolerogenic DCs are induce antigen-specific Tregs and thereby inhibit autoimmune destruction of beta-cells.
Study design
weeks: 4, 8, 12, 24
Intervention
Two intradermal injections of PIpepTolDCs (5x 10e6, 10x 10e6 or 20 x 10e6/ injection in 3 patients each) with a 28-day interval.
J.J. Zwaginga
Albinusdreef 2
Leiden 2300 RC
The Netherlands
J.J. Zwaginga
Albinusdreef 2
Leiden 2300 RC
The Netherlands
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
• 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 (< 3 months) fasting insulin C-peptide > 200 pmol/L;
• Peak insulin C-peptide < 200 pmol/L after stimulation with Mixed Meal Tolerance Tests (MMTT).
• Recent (< 3 months) HbA1c > 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
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL5425 |
| NTR-old | NTR5542 |
| Other | : ABR48984 |