1. In this randomized controlled trial, two 12-day courses of teplizumab improved C-peptide levels compared to placebo at week 78 in patients with stage 3 type 1 diabetes.
2. No significant differences were observed between the teplizumab and placebo groups regarding secondary clinical outcomes, including clinically relevant hypoglycemic events.
Evidence evaluation level: 1 (great)
research summary: Type 1 diabetes is an autoimmune disease characterized by T-cell-mediated destruction of pancreatic β-cells, posing a significant burden to disease management. Glycemic control tends to be particularly difficult in young patients, whose disease progresses rapidly. Teplizumab, a humanized anti-CD3 monoclonal antibody, was recently approved by the Food and Drug Administration for patients with preclinical type 1 diabetes aged 8 years and older to delay the onset of clinical disease. Previous studies have demonstrated that short-term administration of teplizumab preserves beta-cell function without significantly impacting long-term safety. This trial investigated whether two short courses of teplizumab preserve beta-cell function and improve important clinical outcomes in children with newly diagnosed stage 3 type 1 diabetes. Overall, teplizumab was demonstrated to improve C-peptide levels compared to placebo at his 78th week, suggesting preservation of beta-cell function. Furthermore, no significant differences were observed between the teplizumab and placebo groups with respect to secondary clinical outcomes such as mean insulin dose, change in glycated hemoglobin, percentage of time within target blood glucose range, and clinically relevant hypoglycemic events. There wasn't. The generalizability of the study results was limited by the lack of ethnic diversity among the participants.
detail [randomized controlled trial]: Provention Bio's Type 1 Diabetes Trial, Evaluation of C-Peptide with Teplizumab (PROTECT), is a randomized, phase 3 study evaluating the efficacy of teplizumab in preserving beta-cell function in young patients with newly diagnosed type 1 diabetes. This is a placebo-controlled trial. Patients aged 8 to 17 years diagnosed with stage 3 disease within 6 weeks were selected. A total of 328 participants were enrolled and, 26 weeks apart, were randomly assigned to receive either teplizumab or placebo in a 2:1 ratio over two 12-day courses. . A cumulative dose of 9 mg per square meter was administered to each individual. The primary endpoint was defined as the change from baseline in C-peptide levels at week 78, with levels measured from the area under the concentration-time curve (AUC) during a 4-hour mixed meal tolerance test. Secondary clinical endpoints included mean daily insulin dose, change in glycated hemoglobin, percentage of time within target blood glucose range, and clinically relevant hypoglycemic events. Treatment with teplizumab resulted in significantly higher C-peptide AUC levels compared with placebo at week 78 (least squares mean difference, 0.13 pmol per milliliter, 95% confidence interval) [CI], 0.09 to 0.17. p<0.001). More specifically, 94.9% (95% CI, 89.5 to 97.6) of patients treated with teplizumab had clinical showed a meaningful peak C peptide concentration of 0.2 pmol/mm or more. 87.4). No significant differences were observed for secondary endpoints, including clinically significant hypoglycemic events. In summary, the PROTECT study showed that his two short courses of teplizumab were effective in preserving beta-cell function but not in improving important clinical outcomes.
