Teplizumab preserves beta-cell function for children with new-onset type 1 diabetes
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Key takeaways:
- Children recently diagnosed with type 1 diabetes had a higher C-peptide level at 78 weeks with teplizumab vs. placebo.
- No differences in HbA1c, time in range or mean insulin dose were observed.
Children with new-onset type 1 diabetes had better preservation of beta-cell function with two 12-day courses of teplizumab compared with those receiving placebo, according to findings published in The New England Journal of Medicine.
“Treatment with teplizumab (Tzield, Provention Bio) administered intravenously every day for two 12-day courses resulted in benefits with respect to the primary endpoint of maintenance of beta-cell function,” Kevan Herold, MD, C.N.H. Long professor of immunobiology and medicine (endocrinology) at Yale School of Medicine, and colleagues wrote. “However, it did not result in significant differences with respect to the key secondary endpoints.”
Researchers conducted a phase 3 double-blind randomized controlled trial at 61 sites in the U.S., Canada and Europe. Children and adolescents aged 8 to 17 years with stage 3 type 1 diabetes who were diagnosed within 6 weeks of randomization were enrolled. Participants were randomly assigned, 2:1, to receive two 12-day courses of intravenous teplizumab or placebo. The two courses were administered 26 weeks apart. A 4-hour mixed-meal tolerance test was conducted to assess C-peptide levels at baseline and 78 weeks. Participants wore a continuous glucose monitor to assess time in glucose range and other CGM metrics during the study. Insulin doses and hypoglycemia were self-reported in an electronic diary. The primary outcome of the study was the change in C-peptide levels from baseline to 78 weeks.
There were 328 participants in the study, of whom 217 received teplizumab and 111 received placebo. The teplizumab group had a greater increase in C-peptide levels from baseline to 78 weeks compared with placebo (least-squares mean difference, 0.13 pmol/mL; 95% CI, 0.09-0.17). In an exploratory analysis, 94.9% of children and adolescents in the teplizumab group had a peak C-peptide level of 0.2 pmol/mL or higher at 78 weeks compared with 79.2% of the placebo group.
No differences between the teplizumab and placebo groups were observed for HbA1c, time in range and mean insulin dose. After 12 weeks, the mean insulin dose was lower for those receiving teplizumab compared with placebo.
Adverse events were reported by 99.5% of participants in the teplizumab group and 97.3% of those receiving placebo. Most of the adverse events were mild or moderate in severity. The proportion of children and adolescents who had adverse events leading to treatment discontinuation was 6.9% in the teplizumab group and 2.7% in the placebo group.
“The side effects of teplizumab observed in the present trial included headache, gastrointestinal symptoms, rash, lymphopenia and mild cytokine release syndrome,” the researchers wrote. “These findings were consistent with previous experience, and the events resolved spontaneously.”
Severe hypoglycemia occurred in 13.4% of the teplizumab group and 16.2% of the placebo group. No events of diabetic ketoacidosis were reported. Epstein-Barr virus reactivation occurred in eight children receiving teplizumab and was asymptomatic in six of those eight. All events resolved without antiviral treatment.
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