Table 5

Tertiary prevention trials of combination immunotherapy after diagnosis of diabetes

Study (ref.)Drug/phaseSponsor/contactAge (years)Time from diagnosis/eligibilityRouteDosingTreated: placeboFollow-up duration/primary end pointStatus/target size
TrialNet MMF/DZB (107)Mycophenolate mofetil & daclizumab/phase IIINIH, NIDDK, TrialNet/diabetestrialnet.org8–45≤12 weeks/C-peptide* ≥0.2 pmol/mlMMF 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 mg2:14 years/MMTT C-peptideEnrollment closed/n = 126
03-DK-0245 (108)exenatide & daclizumab/phase IINIH, NIDDK, Amylin Pharmaceuticals/1-800-411-1222 (Amylin), prpl@mail.cc.nih.gov18–60>5 years/C-peptide* 0.3–1.2 ng/mlExendin-4 s.c., DZB i.v.2 × 2 factorial20 weeksEnrollment closed/n = 16
Proleukin + rapamune (109)hrIL-2 (aldesleukin) & sirolimus/phase INIH, NIAID ITN/diabetes@benaroyaresearch.org18–453–48 monthshrIL-2 s.c., sirolimus p.o.hrIL-2 4.5 × 106 IU/day three times weekly for 4 weeks, sirolimus escalating dose for 12 weeksOpen label2 years/adverse events MMTT C-peptideEnrolling/n = 10
09-DK-0056 (75)Sitagliptin/lansoprazole rhGAD65 (Diamyd)/phase IINIH, NIDDK, Diamyd Therapeutics/1-800-411-1222 (Diamyd), prpl@mail.cc.nih.gov, davidmh@intra.niddk.nih.gov16–30≤4 months/C-peptide ≥0.2 pmol/mlSitagliptin p.o., rhGAD65 s.c.MMTT C-peptideEnrolling/n = 164
E1-INT (110)EGF and gastrin/phase IITransition therapeutics/Aleksandra Pastrak, MD18–40>1 years.c.Daily for 4 weeks3:16 months/Arg-stimulated C-peptideEnrollment closed/n = 20
Sao Paulo (64,65)Autologous stem cell transplantation and cyclophosphamide + rabbit ATG/phase IIUniversity of Sao Paulo, Northwestern University, Genzyme/jvoltar@fmrp.usp.br14–31≤6 weeksi.v.Cyclophosphamide 200 mg/kg, rabbit ATG 4.5 mg/kgOpen label3 years/adverse events, insulin dosePublished/n = 20
Shanghai (67)Autologous stem cell transplantation and cyclophosphamide + rabbit ATG/phase IIShanghai JiaoTong University/guangning@medmail.com.cn14–35≤6 monthsi.v.Cyclophosphamide 200 mg/kg, rabbit ATG 4.5 mg/kgOpen label3 years/insulin doseEnrolling/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.