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Teplizumab and β-Cell Function in Newly Diagnosed Type 1 Diabetes
EL. Ramos, CM. Dayan, L. Chatenoud, Z. Sumnik, KM. Simmons, A. Szypowska, SE. Gitelman, LA. Knecht, E. Niemoeller, W. Tian, KC. Herold, PROTECT Study Investigators
Language English Country United States
Document type Randomized Controlled Trial, Clinical Trial, Phase III, Journal Article
NLK
ProQuest Central
from 1980-01-03 to 3 months ago
Nursing & Allied Health Database (ProQuest)
from 1980-01-03 to 3 months ago
Health & Medicine (ProQuest)
from 1980-01-03 to 3 months ago
Family Health Database (ProQuest)
from 1980-01-03 to 3 months ago
Psychology Database (ProQuest)
from 1980-01-03 to 3 months ago
Health Management Database (ProQuest)
from 1980-01-03 to 3 months ago
Public Health Database (ProQuest)
from 1980-01-03 to 3 months ago
PubMed
37861217
DOI
10.1056/nejmoa2308743
Knihovny.cz E-resources
- MeSH
- CD3 Complex antagonists & inhibitors immunology MeSH
- Insulin-Secreting Cells drug effects immunology MeSH
- C-Peptide analysis MeSH
- Diabetes Mellitus, Type 1 * diagnosis immunology therapy MeSH
- Child MeSH
- Double-Blind Method MeSH
- Antibodies, Monoclonal, Humanized * adverse effects pharmacology therapeutic use MeSH
- Hypoglycemic Agents administration & dosage therapeutic use MeSH
- Insulin administration & dosage therapeutic use MeSH
- Humans MeSH
- Adolescent MeSH
- Disease Progression MeSH
- T-Lymphocytes drug effects immunology MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Randomized Controlled Trial MeSH
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.).
Cardiff University Cardiff United Kingdom
From Provention Bio a Sanofi company Red Bank NJ
the Barbara Davis Center for Diabetes University of Colorado School of Medicine Aurora
the Departments of Immunobiology and Internal Medicine Yale University New Haven CT
the Medical University of Warsaw Warsaw Poland
the University of California San Francisco San Francisco
Université Paris Cité CNRS INSERM Institut Necker Enfants Malades INEM Paris
References provided by Crossref.org
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- $a Ramos, Eleanor L $u From 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.)
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- $a Teplizumab and β-Cell Function in Newly Diagnosed Type 1 Diabetes / $c EL. Ramos, CM. Dayan, L. Chatenoud, Z. Sumnik, KM. Simmons, A. Szypowska, SE. Gitelman, LA. Knecht, E. Niemoeller, W. Tian, KC. Herold, PROTECT Study Investigators
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- $a 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.).
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- $a Dayan, Colin M $u From 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.)
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