Herold, K. C., Dayan, C. M.  ORCID: https://orcid.org/0000-0002-6557-3462, Kordonouri, O., Chatenoud, L., Gitelman, S. E., Šumník, Z., Simmons, K. M., Szypowska, A., Knecht, L. A., Niemoeller, E., Tian, W. and Ramos, E. L.
2025.
PROTECT per-protocol analysis: Preservation of β-cell function in children and adolescents with newly diagnosed type 1 diabetes stage 3.
Diabetologie und Stoffwechsel
20
(S 01)
, S40-S41.
10.1055/s-0045-1807433
|
Abstract
Objective : Teplizumab is an anti-CD3 monoclonal antibody approved in the US for delaying the onset of type 1 diabetes (T1D) stage 3 in individuals aged ≥8 years with T1D stage 2. In the intent-to-treat (ITT) population of the PROTECT trial, teplizumab demonstrated significantly better preservation of β-cell function vs. placebo (PBO; the least squares mean (LSM) difference in C-peptide ln (AUC+1) change from baseline (BL) to week 78 between teplizumab and PBO was 0.13 pmol/ml; p<0.001). In the ITT population, insulin dose was lower with teplizumab vs. PBO starting at week 12. Here, we investigate insulin dose reduction and sustained glycemic control in the per-protocol (PP) population. Methods : The phase 3 PROTECT trial (NCT03875729) in 8- to 17-year-olds with stage 3 T1D, diagnosed for ≤6 weeks, with ≥1 T1D-associated autoantibody and peak C-peptide levels ≥0.2 pmol/ml, randomized participants 2:1 to two 12-day cycles of teplizumab or PBO. The PP population excluded those who received incorrect treatment, took prohibited medications, became pregnant, or had <80% treatment compliance. Results : In the PP analysis, teplizumab showed consistent results with the ITT analysis for insulin use: it was almost unchanged with teplizumab (LSM (95% confidence interval (CI)): 0.45 (0.39; 0.50) units (U)/kg/day(d)) vs. an increase in PBO (0.61 (0.54; 0.69) U/kg/d), resulting in a LSM difference (95% CI) of -0.17 (-0.26; -0.08) U/kg/d (p<0.001). The teplizumab group spent a greater percentage of time in target range (TIR) than the PBO group (LSM (95% CI): 67.6 (64.1; 71.1)% vs. 61.4 (56.5; 66.4)%; LSM difference: 6.17 (0.13; 12.2)%; p=0.045). HbA1c values did not differ significantly between groups: change in LSM (95% CI) vs. BL -2.07 (-2.27; -1.87)% in the teplizumab group vs. -1.94 (-2.21; -1.67)% in the PBO group, LSM difference (95% CI) -0.13 (-0.46; 0.20)% (p=0.454). C-peptide levels, determined by the area under the curve (AUC), analyzed using the natural logarithm ln(AUC+1), were significantly higher with teplizumab vs. PBO in the PP analysis, consistent with the results of the ITT analysis; the change in LSM (95% CI) vs. BL was -0.08 (-0.10; -0.06) pmol/ml for teplizumab vs. -0.22 (-0.25; -0.19) pmol/ml for PBO, LSM difference (95% CI) 0.14 (0.10; 0.18) pmol/ml (p<0.001). C-peptide levels at week 78 were mean±standard deviation 0.46±0.19 pmol/ml (teplizumab; n=165) vs. 0.33±0.21 pmol/ml (PBO; n=82). Conclusion : Participants treated with teplizumab demonstrated better preservation of β-cell function and clinically relevant metabolic outcomes, including lower insulin doses and more TIR vs. PBO.
| Item Type: | Article |
|---|---|
| Date Type: | Published Online |
| Status: | Published |
| Schools: | Schools > Medicine |
| Publisher: | Thieme Gruppe |
| ISSN: | 1861-9002 |
| Last Modified: | 17 Jun 2025 10:45 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/179110 |
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