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Teplizumab and β-Cell Function in Newly Diagnosed Type 1 Diabetes
Eleanor L Ramos1, Colin M Dayan1, Lucienne Chatenoud1
1From Provention Bio, a Sanofi company, Red Bank, NJ (E.L.R., L.A.K., W.T.); Cardiff University, Cardiff, United Kingdom (C.M.D.); Université Paris Cité, CNRS, INSERM, Institut Necker Enfants Malades-INEM, Paris (L.C.); the Department of Pediatrics, Motol University Hospital, Second Faculty of Medicine-Charles University, Prague, Czech Republic (Z.S.); the Barbara Davis Center for Diabetes/University of Colorado School of Medicine, Aurora (K.M.S.); the Medical University of Warsaw, Warsaw, Poland (A.S.); the University of California, San Francisco, San Francisco (S.E.G.); Sanofi, Frankfurt, Germany (E.N.); and the Departments of Immunobiology and Internal Medicine, Yale University, New Haven, CT (K.C.H.).
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.).
Insights
Teplizumab treatment in children and adolescents with newly diagnosed type 1 diabetes demonstrated improved beta-cell function preservation. However, secondary clinical endpoints did not show significant differences between the teplizumab and placebo groups.
Area of Science:
- Immunology
- Endocrinology
- Clinical Trials
Background:
- Teplizumab is an FDA-approved monoclonal antibody for delaying clinical type 1 diabetes in preclinical stages.
- Its efficacy in preventing disease progression in newly diagnosed type 1 diabetes is not yet established.
Purpose of the Study:
- To assess the impact of intravenous teplizumab on beta-cell preservation in children and adolescents with newly diagnosed type 1 diabetes.
- To evaluate clinical endpoints and safety profiles associated with teplizumab treatment.
Main Methods:
- A phase 3, randomized, placebo-controlled trial involving two 12-day courses of teplizumab or placebo.
- Primary endpoint: change in stimulated C-peptide levels at week 78.
- Secondary endpoints: insulin dosage, glycated hemoglobin, time in glucose range, and hypoglycemia events.
Main Results:
- Teplizumab treatment resulted in significantly higher stimulated C-peptide levels at week 78 compared to placebo.
- A higher percentage of teplizumab-treated patients maintained clinically meaningful peak C-peptide levels.
- No significant differences were observed in key secondary clinical endpoints between the groups.
Conclusions:
- Two courses of teplizumab showed a benefit in preserving beta-cell function in newly diagnosed type 1 diabetes.
- No significant differences were found for secondary clinical endpoints, indicating a need for further research.
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