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Teplizumab (Tzield) infusions in children and adolescents with new-onset type 1 diabetes met the primary endpoint of preserved beta-cell function and trended toward improved secondary glycemic endpoints.
- The study was a phase 3, randomized, placebo-controlled trial of teplizumab (n = 217) vs placebo (n = 111) in children and adolescents aged 8-17 years within 6 weeks of clinical type 1 diabetes (stage 3) onset.
- Teplizumab or placebo was given in two 12-day infusions, 26 weeks apart.
- The primary endpoint was change in beta-cell function, as measured by stimulated C-peptide level at 78 weeks.
- Key secondary endpoints were insulin doses required to meet glycemic goals, A1c levels, time in target glucose range, and clinically significant hypoglycemic events.
- Patients randomly assigned to receive teplizumab had significantly higher stimulated C-peptide levels than did patients assigned to placebo at week 78, with a difference of 0.13 pmol/mL (P < .001).
- Clinically meaningful peak C-peptide levels ≥ 0.2 pmol/L were achieved in 94.9% of teplizumab recipients vs 79.2% of placebo recipients.
- The two groups did not differ significantly in any of the key secondary endpoints.
- Adverse events occurred in 99.5% of patients with teplizumab and 97.3% of patients with placebo; these included headache, gastrointestinal symptoms, rash, and lymphopenia.
- Mild cytokine release syndrome occurred in two patients receiving teplizumab and resolved within 7 days.
- Adverse events leading to treatment discontinuation occurred in 6.9% of the teplizumab group and 2.7% of the placebo group.
- Severe hypoglycemia occurred in 13.4% of patients receiving teplizumab and 16.2% of patients receiving placebo.
- Teplizumab, a humanized monoclonal antibody to CD3 on T cells, was approved by the US Food and Drug Administration in November 2022 to delay the onset of clinical type 1 diabetes in patients aged 8 years or older with preclinical (stage 2) disease.
- "There's been discussion for a few years about what regulatory agencies might be looking for in studies of new-onset diabetes. [Secondary endpoint data] collected in this trial…are all trending in the same direction even though they don't meet a statistical P value," lead author Kevan C. Herold, MD, of Yale University, told Medscape Medical News.
- Herold, who conducted a previous trial of teplizumab in people with new-onset type 1 diabetes, added, "This confirmed what had been found in the earlier trials that basically indicate that this drug works. And it works whenever you give it."
- However, he also noted, "Pediatric endocrinologists and primary care providers should think about finding people [with preclinical type 1 diabetes] as early as possible."
The study was published October 18, 2023 in The New England Journal of Medicine. The lead author is Eleanor L. Ramos, MD, of Provention Bio, a Sanofi company, Red Bank, New Jersey.
The trial was complicated by the COVID-19 pandemic. The study population was mostly White. There was possible unblinding to the investigators. The study was probably underpowered for secondary endpoints.
The study was funded by Provention Bio, a Sanofi company.
Teplizumab, a humanized monoclonal antibody to CD3 on T cells, is approved by the Food and Drug Administration to delay the onset of clinical type 1 diabetes (stage 3) in patients 8 years of age or older with preclinical (stage 2) disease. Whether treatment with intravenous teplizumab in patients with newly diagnosed type 1 diabetes can prevent disease progression is unknown.
In this phase 3, randomized, placebo-controlled trial, we assessed β-cell preservation, clinical end points, and safety in children and adolescents who were assigned to receive teplizumab or placebo for two 12-day courses. The primary end point was the change from baseline in β-cell function, as measured by stimulated C-peptide levels at week 78. The key secondary end points were the insulin doses that were required to meet glycemic goals, glycated hemoglobin levels, time in the target glucose range, and clinically important hypoglycemic events.
Patients treated with teplizumab (217 patients) had significantly higher stimulated C-peptide levels than patients receiving placebo (111 patients) at week 78 (least-squares mean difference, 0.13 pmol per milliliter; 95% confidence interval [CI], 0.09 to 0.17; P<0.001), and 94.9% (95% CI, 89.5 to 97.6) of patients treated with teplizumab maintained a clinically meaningful peak C-peptide level of 0.2 pmol per milliliter or greater, as compared with 79.2% (95% CI, 67.7 to 87.4) of those receiving placebo. The groups did not differ significantly with regard to the key secondary end points. Adverse events occurred primarily in association with administration of teplizumab or placebo and included headache, gastrointestinal symptoms, rash, lymphopenia, and mild cytokine release syndrome.
Two 12-day courses of teplizumab in children and adolescents with newly diagnosed type 1 diabetes showed benefit with respect to the primary end point of preservation of β-cell function, but no significant differences between the groups were observed with respect to the secondary end points. (Funded by Provention Bio and Sanofi; PROTECT ClinicalTrials.gov number, NCT03875729
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