|
| Antigen type | Antigen | Formulation | Route | Trial (Phase) | Subjects | Outcome and/or immune biomarkers | Reference |
|
| Protein | Insulin | Short-acting insulin | Intravenous | Intravenous insulin (Phase I) | Recent-onset T1D | Higher stimulated C peptide and lower HbA1c versus s.c. NPH insulin | [38] |
| Protein | Insulin | (Ultra)lente/regular insulin (s.c.) + short-acting insulin (i.v.) | Subcutaneous + Intravenous | Joslin Insulin Prophylaxis Trial (Phase I) | At risk | Suggestive of efficacy | [39] |
| Protein | Insulin | Lente/short-acting insulin (s.c.) + short-acting insulin (i.v.) | Subcutaneous + Intravenous | Schwabing Insulin Prophylaxis Trial (Phase I) | At risk | Suggestive of efficacy | [40] |
| Protein | Insulin | Ultralente insulin (s.c.) + short-acting insulin (i.v.) | Subcutaneous + Intravenous | DPT-1 Parenteral arm (Phase III) | At risk | No effect | [41] |
| Protein | Insulin | Ultralente insulin | Subcutaneous | EPPSCIT (Phase II) | At risk | No effect | [42] |
| Protein | Insulin | Short-acting insulin | Oral | ORALE (Phase II) | Recent-onset T1D | No effect | [46] |
| Protein | Insulin | Short-acting insulin | Oral | IMDIAB VII
(Phase II) | Recent-onset T1D | No effect | [47] |
| Protein | Insulin | Short-acting insulin | Oral | DPT-1 Oral arm (Phase III) | At risk | Some efficacy in IAA+ subjects | [49] |
| Protein | Insulin | Short-acting insulin | Oral | Oral insulin tolerance
(Phase III) | Recent-onset T1D | 1 mg improved C-peptide responses in older patients;10 mg accelerated C-peptide decline in younger patients | [48] |
| Protein | Insulin | Short-acting insulin | Oral | NIH/ADA/JDRF oral insulin (Phase III) | At-risk IAA+ | Ongoing | NCT 00419562 |
| Protein | Insulin | Short-acting insulin | Intranasal | INIT-I (Phase I) | At-risk IAA+ | Increase in aAb and decrease in T-cell proliferative responses to insulin | [50] |
| Protein | Insulin | Short-acting insulin | Intranasal | DIPP (Phase III) | At risk | No effect | [51] |
| Protein | Insulin | Short-acting insulin | Intranasal | Intranasal insulin in T1D patients
(Phase II) | Recent-onset, non-insulin-dependent T1D | No effect; decrease in IFN-γ T-cell responses to PI; decrease in Ab responses to exogenous insulin | [52] |
| Protein | Insulin | Short-acting insulin | Intranasal | INIT-II (Phase II) | At risk with preserved 1st phase insulin response | Ongoing | NCT 00336674 |
| Protein | Insulin | Short-acting insulin | Oral or Intranasal | Pre-POINT | IAA- chidren at high genetic risk for T1D | Planned | [123] |
| Protein | GAD | Recombinant GAD in alum (Diamyd) | Subcutaneous | Swedish Diamyd (Phase II) | Recent-onset T1D | Slower decline in fasting and stimulated C-peptide secretion; increase in anti-GAD aAbs and in FowP3 and TGF-β mRNA | [32] |
| Protein | GAD | Recombinant GAD in alum (Diamyd) | Subcutaneous | EU Diamyd
(Phase III) | Recent-onset T1D | Ongoing | NCT 00723411 |
| Protein | GAD | Recombinant GAD in alum (Diamyd) | Subcutaneous | US Diamyd (DIAPREVENT) (Phase III) | Recent-onset T1D | Ongoing | NCT 00751842 |
| Protein | GAD | Recombinant GAD in alum | Subcutaneous | NIDDK/ADA/JDRF GAD-alum
(Phase II) | Recent-onset T1D | Ongoing | NCT 00529399 |
| Protein | GAD | Recombinant GAD in alum (Diamyd) | Subcutaneous | DIAPREV-IT
(Phase II) | At risk, GAD aAb++ ≥1 other aAb | Ongoing | NCT 01122446 |
| Peptide | Insulin | Insulin B chain in incomplete Freund’s adjuvant | Intramuscular | IBC-VS01 (Phase I) | Recent-onset IAA+ T1D | Increased TGF-β production | [66] |
| Peptide | Proinsulin | PIC19- A3 | Intradermal | PI peptide immunotherapy (Phase I) | Long-standing T1D | Transient PI-specific IL-10 secretion in 3/18 patients at 30 g | [67] |
| Modified peptide | Insulin | NBI-6024 ( APL) | Subcutaneous | NBI-6024-0003 (Phase I) | Recent-onset T1D | Shift from Th1 to Th2 responses | [76] |
| Modified peptide | Insulin | NBI-6024 ( APL) | Subcutaneous | Neurocrine NBI-6024
(Phase II) | Recent-onset T1D | No effect | [77] |
| Modified protein | Insulin | Insulin-coupled ECDI-fixed autologous leukocytes | ? | ITN insulin-coupled leukocytes | At risk | Planned | [86] |
| DNA plasmid | Proinsulin | BHT-3021 (PI plasmid) | Intramuscular | Bayhill BHT-3021 (Phase I) | Recent-onset T1D | Ongoing | NCT 00453375 |
| Ag-specific cell therapy | None | Autologous monocyte-derived DCs treated with CD40/CD80/CD86 antisense oligonucleotides | Intradermal | Pittsburgh DC vaccine (Phase I) | Long-standing T1D | Ongoing | NCT 00445913 |
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