TOPLINE:
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.
METHODOLOGY:
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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.
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Teplizumab or placebo was given in two 12-day infusions, 26 weeks apart.
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The primary endpoint was change in beta-cell function, as measured by stimulated C-peptide level at 78 weeks.
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Key secondary endpoints were insulin doses required to meet glycemic goals, A1c levels, time in target glucose range, and clinically significant hypoglycemic events.
TAKEAWAY:
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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).
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Clinically meaningful peak C-peptide levels ≥ 0.2 pmol/L were achieved in 94.9% of teplizumab recipients vs 79.2% of placebo recipients.
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The two groups did not differ significantly in any of the key secondary endpoints.
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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.
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Mild cytokine release syndrome occurred in two patients receiving teplizumab and resolved within 7 days.
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Adverse events leading to treatment discontinuation occurred in 6.9% of the teplizumab group and 2.7% of the placebo group.
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Severe hypoglycemia occurred in 13.4% of patients receiving teplizumab and 16.2% of patients receiving placebo.
IN PRACTICE:
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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.
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“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.
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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.”
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However, he also noted, “Pediatric endocrinologists and primary care providers should think about finding people [with preclinical type 1 diabetes] as early as possible.”
SOURCE:
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.
LIMITATIONS:
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.
DISCLOSURES:
The study was funded by Provention Bio, a Sanofi company.
Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She is on Twitter @MiriamETucker.
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