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Phase 2CompletedNCT02215200

Low-dose anti-thymocyte globulin (ATG) ± GCSF in new-onset T1D (Haller / TrialNet)

A TrialNet Phase 2 trial testing whether a single, brief course of low-dose anti-thymocyte globulin (ATG) — with or without GCSF — can slow the immune destruction of insulin-making cells in people newly diagnosed with type 1 diabetes. Low-dose ATG alone preserved C-peptide and lowered HbA1c out to two years; adding GCSF did not help.

Primary endpoints

  • Mean area under the curve (AUC) C-peptide during a 2-hour mixed-meal tolerance test at 12 months

Results so far

Low-dose ATG alone worked best. At 1 year, mean stimulated C-peptide was significantly higher with ATG (0.646 nmol/L) than placebo (0.406 nmol/L) (p=0.0003); ATG+GCSF (0.528 nmol/L) was not significantly better than placebo. The benefit of ATG alone persisted at 2 years (p=0.00005 vs placebo), while ATG+GCSF again fell short of the prespecified significance threshold. HbA1c was significantly reduced at both 1 and 2 years with ATG and with ATG+GCSF. Immune testing showed ATG shifted T-cell ratios toward a more regulatory (less self-attacking) profile.

The full picture

What was tested, and why it matters

In type 1 diabetes, the immune system destroys the insulin-making "beta" cells in the pancreas. At diagnosis, most people still have some working beta cells — and protecting that residual function makes blood sugar easier to control and lowers the risk of complications. This trial asked whether a short, one-time immune-calming treatment, given soon after diagnosis, could slow that destruction.1

The drug, anti-thymocyte globulin (ATG), temporarily depletes the T-cells that drive the attack. An earlier pilot study had paired low-dose ATG with GCSF (a drug that mobilizes regulatory immune cells), so this trial tested both: ATG alone and ATG plus GCSF.2

Who it was for

The trial enrolled 89 people diagnosed with type 1 diabetes within the previous 100 days, aged over 12 and under 46, who still had detectable insulin production and at least one positive islet autoantibody.13

How it was designed

This was a three-arm, randomized, double-masked, placebo-controlled Phase 2 trial run by the NIH-funded TrialNet network across US centers.13 Participants received low-dose ATG (2.5 mg/kg) plus GCSF (29 people), low-dose ATG alone (29 people), or placebo (31 people).2 The main measure was preserved insulin production — C-peptide during a mixed-meal test — at 1 year, with follow-up to 2 years.12

The key results

Low-dose ATG alone was the clear winner. At 1 year, preserved C-peptide was significantly higher with ATG (0.646 nmol/L) than placebo (0.406 nmol/L), while ATG+GCSF (0.528 nmol/L) was not significantly better than placebo.2 The benefit of ATG alone held at 2 years.1 HbA1c (average blood sugar) was significantly lower with both ATG and ATG+GCSF versus placebo at both time points.12 Immune profiling showed ATG shifted T-cells toward a more regulatory, less self-destructive balance.1

What it means and what's next

A single low-dose ATG course — without ongoing immunosuppression — meaningfully protected beta-cell function for two years, and adding GCSF did not help.12 The authors concluded that low-dose ATG should be studied for preventing or delaying type 1 diabetes in at-risk people before diagnosis, not just treating it after.1

References

  1. Haller MJ, Long SA, Blanchfield JL, et al. Low-Dose Anti-Thymocyte Globulin Preserves C-Peptide, Reduces HbA1c, and Increases Regulatory to Conventional T-Cell Ratios in New-Onset Type 1 Diabetes: Two-Year Clinical Trial Data. Diabetes (2019);68(6):1267–1276. https://doi.org/10.2337/db19-0057 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9

  2. Haller MJ, Schatz DA, Skyler JS, et al. Low-Dose Anti-Thymocyte Globulin (ATG) Preserves β-Cell Function and Improves HbA1c in New-Onset Type 1 Diabetes. Diabetes Care (2018);41(9):1917–1925. https://doi.org/10.2337/dc18-0494 ↩ ↩2 ↩3 ↩4 ↩5 ↩6

  3. National Institute of Diabetes and Digestive and Kidney Diseases (TrialNet). Antithymocyte Globulin (ATG) and Pegylated Granulocyte Colony Stimulating Factor (GCSF) in New Onset Type 1 Diabetes. ClinicalTrials.gov NCT02215200 (2014–2018). https://clinicaltrials.gov/study/NCT02215200 ↩ ↩2