Table 3

Tertiary prevention trials of systemic immunomodulation after diagnosis of diabetes

Study (ref.)Drug/phaseSponsor/contactAge (years)Time from diagnosis/eligibilityRouteDosingTreated:placeboFollow-up duration/primary end pointStatus/target size
TTEDD (89)Anti-CD3 (TRX4)/phase IITolerX Inc., JDRF/ and clinicaltrials@tolerx.com18–45Any duration/C-peptide detectablei.v.8 daily injectionsAll:04 years/define highest tolerated doseEnrolling/n = 100
DEFEND (59)Anti-CD3 (otelixizumab)/phase IIITolerX Inc., JDRF/ and defend@tolerx.com18–35≤12 weeks/C-peptide 0.2–3.5 pmol/mli.v.8 daily injections2:12 years/MMTT C-peptideEnrolling/n = 240
AbATE (90)Anti-CD3 (teplizumab)/phase IINIH, NIAID ITN/info@abatetrial.org8–30<8 weeksi.v.14 daily injections/escalation dose; 2nd course after 12 months2:1/open label2 years/MMTT C-peptide (4-h AUC)Enrolling/n = 81
Delay (91)Anti-CD3 (teplizumab)/phase IINIH, NIDDK, JDRF/kevan.herold@yale.edu8–304–12 months/C-peptide* ≥0.2 pmol/mli.v.14 daily injections/escalation dose; 2nd course after 12 months1:11 year/MMTT C-peptide (4-h AUC)Enrolling/n = 60
Protégé (92)Anti-CD3 (teplizumab)/phase IIMacroGenics, Inc., JDRF/aknesel@mmgct.com8–35: 12–17, 8–11≤12 weeks/C-peptide detectablei.v.14 daily injections/2nd course after 6 months3:12 years/insulin dose + A1C MMTT C-peptideEnrolling/n = 530
TrialNet Rituximab (93)Anti-CD20 (rituximab)/phase IINIH, NIDDK, TrialNet, et al./diabetestrialnet.org8–45≤12 weeks/C-peptide* ≥0.2 pmol/mli.v.4 weekly injections of 375 mg/m2 each2:12 years/MMTT C-peptideEnrollment closed/n = 87
START (94)ATG/phase IINIH, NIAID ITN/info@type1diabetestrial.org12–35≤6 weeks/C-peptide* >0.4 pmol/mli.v.4 daily injections/escalation dose2:12 years/MMTT C-peptideEnrolling/n = 66
ATG (95,96)ATG/phase IIMinistry of Health Czech Republic/frsa@medicon.cz15–35≤6 weeks/C-peptide* ≥0.3 pmol/mli.v.4 daily injections1:13 years/C-peptideEnrollment closed/n = 28
TrialNet Abatacept (97)Anti–CTLA-4NIH, NIDDK, TrialNet, et al./diabetestrialnet.org6–45≤12 weeks/C-peptide* ≥0.2 pmol/mli.v.10 mg/kg monthly injections for 2 years (27 doses)2:12 + 2 years/MMTT C-peptideEnrollment closed/n = 111
Interferon (62)hrIFN-α/phase IINIH, NIDDK/kr58q@nih.gov3–25≤6 weeksp.o.5,000 or 30,000 units once daily for 1 year2:11 year/MMTT C-peptideEnrollment closed/n = 81
Neulasta (98)Pegylated GCSF (pegfilgrastim)/phase I/IIJDRF, University of Florida/hallemj@peds.ufl.edu12–45≤6 months/C-peptide ≥0.2 pmol/mls.c.6 mg weekly for 12 weeks1:12 years/adverse events, MMTT C-peptideEnrolling/n = 21
Anakinra (99)IL-1r antagonist (anakinra)/phase I/IIUniversity of Texas Southwestern Med Center/Soumya Adhikarti, MD6–18≤1 weeks.cDaily for 28 daysOpen labelChange in EGR2 expression by PBMC, C-peptideEnrolling/n = 15
AIDA (100)IL-1r antagonist (anakinra)/phase II/IIIJDRF, Steno Diabetes Center, Oeresund Diabetes Academy/tmpo@steno.dk18–35≤12 weeks/C-peptide* ≥0.2 pmol/mls.c.100 mg once daily for 2 years1:1?2 years/adverse events, MMTT C-peptideEnrolling/n = 160
Etanercept (61)TNF-α inhibitor (etanercept)/phase I/IIUniversity of Buffalo, Immunex, Amgen/tquattrin@upa.chob.edu7–18≤4 weeks/positive islet autoantibodys.c.0.4 mg/kg up to 25 mg twice weekly for 24 weeks1:124 weeks/change in A1C, MMTT C-peptideEnrollment closed/n = 18
Cord blood (63)Autologous umbilical cord blood transfusion/phase I/IIJDRF, NIH, University of Florida/>1Autologous cord blood storedi.v.One infusionOpen label2 years/MMTT C-peptide, A1C, insulin doseEnrolling/n = 23
Prochymal (101)Adult human mesenchymal stem cells/phase IIOsiris Therapeutics, JDRF/osiris@osiris.com18–302–16 weeks/C-peptide detectablei.v.Infusion once per month for 3 months1:1?2 years/MMTT C-peptideEnrolling/n = 60
AdiStem (102)Autologous adipose-derived stem cells/phase I/IIAdiStem Ltd./lettielucero@yahoo.com16–60≤2 yearsi.v.One infusionOpen labelInsulin dependence/insulin doseEnrolling/n = 30
Dendritic cells (68)Autologous dendritic cells/phase INIH, NIDDK, University of Pittsburgh/brian.copeman@chp.edu18–35>5 yearsi.d.Intradermal injection of cells treated ex vivo with antisense oligonucleotides1:1Adverse eventsEnrolling/n = 15
  • MMTT C-peptide = area under the curve for C-peptide in response to a 2-h mixed meal tolerance test.

  • *Stimulated.

  • †Pending approval by data monitoring committee. AbATE, Autoimmunity-Blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes; AIDA, Anti–Interleukin-1 in Diabetes Action; ATG, anti–T-cell globulin; AUC, area under the curve; IFN, interferon; GCSF, granulocyte colony–stimulating factor; MMTT, mixed-meal tolerance test; NIAID ITN, National Institute of Allergy and Infectious Diseases Immune Tolerance Network; NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases; NIH, National Institutes of Health; PBMC, peripheral blood mononuclear cell; JDRF, Juvenile Diabetes Research Foundation; START, Study of Thymoglobulin to Arrest Newly Diagnosed Type 1 Diabetes; TNF-α, tumor necrosis factor-α; TTEDD, TRX4 Monoclonal Antibody in Type 1 Diabetes.