In the PROTECT trial, teplizumab preserved β-cell function in newly diagnosed type 1 diabetes patients, slowing the decline of C-peptide levels, but key secondary endpoints, such as time in range and HbA1c, showed numerical trends without statistical significance.
Kevin Herold, MD
Credit: Yale School of Medicine
Use of teplizumab (Tzield) was linked to the preservation of β-cell function in children and adolescents with newly diagnosed type 1 diabetes, according to results of the PROTECT trial.
Presented at the International Society for Pediatric and Adolescent Diabetes (ISPAD) 2023 annual conference, results of the trial suggest use of teplizumab was associated with a significant slowing of the decline of C-peptide levels relative to placebo therapy in people with stage 3 autoimmune type 1 diabetes, but further analysis indicated numerical trends for key secondary endpoints, such as time in range, HbA1c, and total insulin doses, failed to reach statistical significance.1
“Type 1 diabetes is a chronic autoimmune disease, driven by the destruction of the insulin-producing beta cells, and as such, beta cell preservation remains a meaningful unmet need for all patients with diabetes,” said PROTECT principal investigator Kevan Herold, MD, the C.N.H. Long Professor of Immunobiology and of Medicine at Yale School of Medicine.2 “These new results build on the findings from multiple studies across different stages of the disease process, further supporting TZIELD’s potential to modulate the progression of [type 1 diabetes].”
During the 100th anniversary of Leonard Thompson becoming the first human to receive insulin for his type 1 diabetes in 1922, the diabetes community celebrated the ushering in of a new era in management with the US Food and Drug Administration approval of teplizumab for delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes on November 17, 2022. This approval was based on results of the pivotal TN-10 At-Risk trial, which concluded use reduced risk of progression to type 1 diabetes relative to placebo (HR, 0.41 95% CI, 0.22-0.78; P = .006) and also delayed time to diagnosis (59.6 months vs 27.1 months).3
The PROTECT trial was a phase 3, randomized, placebo-controlled trial aimed at assessing the effect of teplizumab use in people with stage 3 type 1 diabetes. With this in mind, the trial enrolled patients and randomized them in a 2:1 ratio to teplizumab or matching placebo for 2, 12-day courses. Investigators pointed out randomization was stratified according to the peak C-peptide level and age.1
The primary outcome of interest for the trial was change from baseline in β-cell function, as measured by stimulated C-peptide levels at week 78. The trial also featured multiple key secondary outcomes, including insulin doses that were required to meet glycemic goals, HbA1c levels, time in the target glucose range, and clinically important hypoglycemic events.1
A total of 228 patients were recruited from 61 sites in North America and Europe from March 2019 through May 2023. Among this cohort, 217 were randomized to teplizumab and 111 were randomized to placebo.1
Upon analysis, results suggested those randomized to teplizumab had significantly higher stimulated C-peptide levels than their counterparts randomized to placebo at week 78 (least-squares mean difference, 0.13 pmol/ml; 95% confidence interval [CI], 0.09 to 0.17; P <.001). Further analysis indicated 94.9% (95% CI, 89.5 to 97.6) of the teplizumab group maintained a clinically meaningful peak C-peptide level of 0.2 pmol/ml, which was only observed in 79.2% (95% CI, 67.7 to 87.4) of those receiving placebo.1
Analysis of secondary endpoints revealed the following:
“The PROTECT results are encouraging, as we believe they showcase the potential for TZIELD to slow down the progression of Stage 3 [type 1 diabetes] in this population, as well as pointing towards favorable trends in relevant aspects for clinicians and people living with type 1 diabetes. We look forward to discussing this new data with the scientific community and regulatory authorities around the world,” added Jose Eduardo Neves, MD, senior vice president and global head of medical affairs at Sanofi.2
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