medwireNews: Early treatment with the anti-CD3 monoclonal antibody teplizumab may help to preserve β-cell function in children and adolescents with newly diagnosed type 1 diabetes, results of the phase 3 PROTECT study show.
Kevan Herold (Yale University, New Haven, Connecticut, USA) and colleagues report in The New England Journal of Medicine that participants given two 12-day courses of intravenous teplizumab (total cumulative dose 9 mg/m2) 26 weeks apart had significantly higher stimulated C-peptide levels, a marker of β-cell function, at week 78 than those given placebo.
The authors explain that although teplizumab is approved by the US Food and Drug Administration to delay the onset of clinical type 1 diabetes (stage 3) in patients aged 8 years or older with preclinical (stage 2) disease, it is unclear whether the treatment can prevent progression in those who have just been diagnosed with clinical disease.
To investigate, they recruited 328 children and adolescents (mean age 12 years, 57% male) from the United States, Canada, and Europe within 6 weeks of being diagnosed with stage 3 type 1 diabetes.
Herold and team found that, at 78 weeks post-treatment, the mean C-peptide area under the concentration-time curve (AUC) had fallen by 0.09 pmol/mL, from a baseline of 0.54 pmol/mL, in the 217 participants randomly assigned to receive teplizumab.
In the 111 participants given placebo, the mean C-peptide AUC fell by 0.21 pmol/mL from a baseline of 0.53 pmol/mL, resulting in a least-squares mean difference in the change from baseline of 0.13 pmol/mL between the two arms. This “represents a 59.3% difference between the groups, favoring teplizumab,” Herold et al remark.
In addition, 94.9% of patients treated with teplizumab maintained a clinically meaningful peak C-peptide level of at least 0.2 pmol/mL during the follow-up period, compared with 79.2% of those given placebo.
However, the investigators note that there were no significant differences between the two groups for the key secondary outcomes of insulin dose required to meet glycemic goals, glycated hemoglobin levels, time in the target glucose range, and clinically important hypoglycemic events.
The majority of patients in both groups experienced at least one adverse event (AE) that was typically mild or moderate (grade 1 or 2) in severity and resolved spontaneously. The most common AEs in both groups were headache, gastrointestinal symptoms, rash, lymphopenia, and mild cytokine release syndrome, which occurred primarily in association with administration of teplizumab or placebo.
Epstein–Barr virus (EBV) reactivation, an AE of special interest, occurred in eight patients treated with teplizumab, with six cases being asymptomatic. There was also one new case of EBV infection in each treatment group, but all cases resolved without antiviral treatment.
Herold et al conclude: “In this trial involving patients with type 1 diabetes, treatment with teplizumab administered intravenously every day for two 12-day courses resulted in benefits with respect to the primary end point of maintenance of β-cell function.”
The study findings were simultaneously published at ISPAD 2023 in Rotterdam, the Netherlands.
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N Engl J Med 2023; doi:10.1056/NEJMoa2308743
ISPAD 49th Annual Conference; Rotterdam, the Netherlands: Oct 18–21, 2023