Teplizumab preserves ß-cell function in children with new-onset T1D

Treatment with teplizumab significantly preserved beta(ß)-cell function, as measured by C-peptide levels, in children and adolescents with new-onset type 1 diabetes (T1D) compared with placebo, according to the PROTECT* study.

“In 2022, teplizumab, a humanized monoclonal antibody to CD3 on T cells, was approved by the FDA to delay the onset of clinical (stage 3) T1D in patients aged ≥8 years with preclinical (stage 2) T1D,” said the researchers.

“[However, it is unknown] whether treatment with intravenous teplizumab in patients with newly diagnosed T1D can prevent disease progression, [particularly in younger populations],” they noted.

This phase III, placebo-controlled trial analysed 328 children and adolescents aged 8–17 years who were newly diagnosed with (stage 3) T1D within 6 weeks prior to randomization. Participants were randomly assigned to receive two 12-day courses, 26 weeks apart, of teplizumab intravenously (n=217) or placebo (n=111).

At week 78, patients treated with teplizumab had significantly higher C-peptide AUC levels than those treated with placebo (0.46 vs 0.34 pmol/mL; least-square [LS] mean difference, 0.13 pmol/mL; p<0.001). [N Engl J Med 2023;389:2151-2161]

In addition, 94.9 percent of the teplizumab-treated patients achieved a clinically meaningful peak C-peptide level of ≥0.2 pmol/mL at week 78 compared with 79.2 percent of the placebo-treated patients.

Key secondary endpoints

The mean glycated haemoglobin level, at 6.97 percent in the teplizumab group and 7.07 percent in the placebo group, was rapidly controlled but did not differ significantly between the treatment groups through week 78.

The mean percentage of time with a target glucose range of 70–180 mg/dL or 3.9–10 mmol/L was also comparable between the teplizumab and placebo groups (LS mean difference, 4.71 percentage points).

Similar rates of clinically important hypoglycaemic events were also observed in both treatment groups at week 78 (4.68 percent [teplizumab] vs 4.24 percent [placebo]).

The mean daily insulin dose was 0.45 units/kg/day in the teplizumab group and 0.60 units/kg/day in the placebo group (LS mean difference, -0.13 units/kg/day).

“[Overall], the secondary endpoints did not meet thresholds for statistical significance [between the treatment groups], and the trial was probably underpowered to address them,” the researchers noted.

Adverse events

Adverse events (AEs) occurred in 99.5 percent of the patients in the teplizumab arm compared with 97.3 percent in the control arm, with 6.9 percent vs 2.7 percent, respectively, leading to treatment discontinuation.

The most common AEs observed with teplizumab were headaches, gastrointestinal symptoms, rash, lymphopenia, and mild cytokine release syndrome, although “these findings were consistent with previous experience, and the events resolved spontaneously,” noted the researchers.

“Of note, our trial focused on children and adolescents, who represent the age groups most affected by T1D and who are considered to have the greatest need for improved treatment,” said the researchers. “These two 12-day courses of teplizumab in children and adolescents with newly diagnosed T1D showed benefit with respect to the primary endpoint of preservation of ß-cell function.”

“In this trial, the FDA and other corresponding authorities accepted the change in ß-cell function alone as the primary endpoint, a strategy that would seem to be indicated for other studies in the future,” wrote Dr Johnny Ludvigsson from the Department of Biomedical and Clinical Sciences at Linköping University, Linköping, Sweden, in an editorial. [N Engl J Med 2023;389:2199-2201]