Table 5.
Tertiary prevention trials of combination immunotherapy after diagnosis of diabetes
| Study (ref.) | Drug/phase | Sponsor/contact | Age (years) | Time from diagnosis/eligibility | Route | Dosing | Treated: placebo | Follow-up duration/primary end point | Status/target size |
|---|---|---|---|---|---|---|---|---|---|
| TrialNet MMF/DZB (107) | Mycophenolate mofetil & daclizumab/phase III | NIH, NIDDK, TrialNet/diabetestrialnet.org | 8–45 | ≤12 weeks/C-peptide* ≥0.2 pmol/ml | MMF p.o., DZB i.v. | MMF twice daily 600 mg/m2 for 2 years, DZB twice in 2 weeks 1 mg/kg up to 100 mg | 2:1 | 4 years/MMTT C-peptide | Enrollment closed/n = 126 |
| 03-DK-0245 (108) | exenatide & daclizumab/phase II | NIH, NIDDK, Amylin Pharmaceuticals/1-800-411-1222 (Amylin), prpl@mail.cc.nih.gov | 18–60 | >5 years/C-peptide* 0.3–1.2 ng/ml | Exendin-4 s.c., DZB i.v. | 2 × 2 factorial | 20 weeks | Enrollment closed/n = 16 | |
| Proleukin + rapamune (109) | hrIL-2 (aldesleukin) & sirolimus/phase I | NIH, NIAID ITN/diabetes@benaroyaresearch.org | 18–45 | 3–48 months | hrIL-2 s.c., sirolimus p.o. | hrIL-2 4.5 × 106 IU/day three times weekly for 4 weeks, sirolimus escalating dose for 12 weeks | Open label | 2 years/adverse events MMTT C-peptide | Enrolling/n = 10 |
| 09-DK-0056 (75) | Sitagliptin/lansoprazole rhGAD65 (Diamyd)/phase II | NIH, NIDDK, Diamyd Therapeutics/1-800-411-1222 (Diamyd), prpl@mail.cc.nih.gov, davidmh@intra.niddk.nih.gov | 16–30 | ≤4 months/C-peptide ≥0.2 pmol/ml | Sitagliptin p.o., rhGAD65 s.c. | MMTT C-peptide | Enrolling/n = 164 | ||
| E1-INT (110) | EGF and gastrin/phase II | Transition therapeutics/Aleksandra Pastrak, MD | 18–40 | >1 year | s.c. | Daily for 4 weeks | 3:1 | 6 months/Arg-stimulated C-peptide | Enrollment closed/n = 20 |
| Sao Paulo (64,65) | Autologous stem cell transplantation and cyclophosphamide + rabbit ATG/phase II | University of Sao Paulo, Northwestern University, Genzyme/jvoltar@fmrp.usp.br | 14–31 | ≤6 weeks | i.v. | Cyclophosphamide 200 mg/kg, rabbit ATG 4.5 mg/kg | Open label | 3 years/adverse events, insulin dose | Published/n = 20 |
| Shanghai (67) | Autologous stem cell transplantation and cyclophosphamide + rabbit ATG/phase II | Shanghai JiaoTong University/guangning@medmail.com.cn | 14–35 | ≤6 months | i.v. | Cyclophosphamide 200 mg/kg, rabbit ATG 4.5 mg/kg | Open label | 3 years/insulin dose | Enrolling/n = 30 |
*Stimulated. ATG, anti–T-cell globulin; DZB, daclizumab; EGF, epidermal growth factor; MMF, mycophenolate mofetil; NIAID ITN, National Institute of Allergy and Infectious Diseases Immune Tolerance Network.