Teplizumab and β-Cell Function in Newly Diagnosed Type 1 Diabetes.

Adolescent Child Humans Diabetes Mellitus, Type 1 C-Peptide Hypoglycemic Agents / adverse effects Antibodies, Monoclonal, Humanized / adverse effects Double-Blind Method

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
07 Dec 2023
Historique:
medline: 7 12 2023
pubmed: 20 10 2023
entrez: 20 10 2023
Statut: ppublish

Résumé

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.).

Sections du résumé

BACKGROUND 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 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 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 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.).

Identifiants

DOI: 10.1056/NEJMoa2308743 PMID: 37861217
pubmed: 37861217
doi: 10.1056/NEJMoa2308743
doi:

Substances chimiques

teplizumab S4M959U2IJ
C-Peptide 0
Hypoglycemic Agents 0
Antibodies, Monoclonal, Humanized 0

Banques de données

ClinicalTrials.gov
['NCT03875729']

Types de publication

Randomized Controlled Trial Clinical Trial, Phase III Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2151-2161

Investigateurs

Philippe Lysy (P)
Bart Keymeulen (B)
Dominique Beckers (D)
Sara Van Aken (S)
Constantin Polychronakos (C)
Thomas G Elliott (TG)
Mary Jetha (M)
Carol Huang (C)
Zdenek Sumnik (Z)
Jaroslav Skvor (J)
Jiri Strnadel (J)
Laure Oilleau-Barral (L)
Jacques Beltrand (J)
Jean-Claude Carel (JC)
Candace Ben Signor (C)
Regis Coutant (R)
Fabienne Dalla-Vale (F)
Pascal Barat (P)
Marie Hoflack (M)
Marc Nicolino (M)
Karine Braun (K)
Brigitte Mignot (B)
Rachel Reynaud (R)
Stephane Perdereau (S)
Reinhard Berner (R)
Norbert Jorch (N)
Karl Otfried Schwab (KO)
Olga Kordonouri (O)
Thomas Meissner (T)
Desiree Dunstheimer (D)
Katharina Warncke (K)
Juergen Grulich-Henn (J)
Kristine Chobanyan-Juergens (K)
Laszlo Blatniczky (L)
Andrea Luczay (A)
Iren Kantor (I)
Eva Hosszu (E)
Katalin H Nagy (KH)
Violetta Csakvary (V)
Agnes Maroti (A)
Tamas Niederland (T)
Mieczyslaw Szalecki (M)
Malgorzata Wajda-Cuszlag (M)
Ewa Pankowska (E)
Malgorzata Mysliwiec (M)
Agnieszka Szypowska (A)
James Greening (J)
John Gregory (J)
Ambika Shetty (A)
Neil Wright (N)
Nilanjana Ray (N)
Stephen Gitelman (S)
Leonard Chuck (L)
Gad Kletter (G)
Bhuvana Sunil (B)
Michael Gottschalk (M)
Kimber Simmons (K)
Stephen Leichter (S)
David Liljenquist (D)
Kashif Latif (K)
Bruce Bode (B)
Teresa Quattrin (T)
Henry Rodriguez (H)
Quentin Van Meter (Q)
Kurt Griffin (K)
Linda DiMeglio (L)
Michael Haller (M)
Carla Greenbaum (C)
Louis Philipson (L)
Neil White (N)
Kevan Herold (K)
Michelle Van Name (M)
Steven Willi (S)
Robert Rapaport (R)
Michael Tansey (M)
William Russell (W)
Wayne Moore (W)
Michael Thompson (M)
David Baidal (D)
Romeu Azevedo (R)
Robert Hoffman (R)
Antoinette Moran (A)
Perrin White (P)
Patrick McCarthy (P)
Jason Gaglia (J)
Luis Casas (L)
Ines Guttmann-Bauman (I)
Ali Calikoglu (A)
Ksenia Tonyushkina (K)
Rushika Conroy (R)
Bracha Goldsweig (B)
Jose Quintos (J)
Kateryna Kotlyarevska (K)
Matthew Benson (M)
Jose Canas (J)
Anuradha Viswanathan (A)
Katherine Kutney (K)
Ramin Alemzadeh (R)
Anzar Haider (A)
Daniel Flynn (D)

Informations de copyright

Copyright © 2023 Massachusetts Medical Society.

Auteurs

Eleanor L Ramos (EL)

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.).

Colin M Dayan (CM)

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.).

Lucienne Chatenoud (L)

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.).

Zdenek Sumnik (Z)

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.).

Kimber M Simmons (KM)

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.).

Agnieszka Szypowska (A)

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.).

Stephen E Gitelman (SE)

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.).

Laura A Knecht (LA)

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.).

Elisabeth Niemoeller (E)

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.).

Wei Tian (W)

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.).

Kevan C Herold (KC)

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.).

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › Teplizumab and β-Cell Function in Newly...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Teplizumab and β-Cell Function in Newly...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Teplizumab and β-Cell Function in Newly...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Diabète de type 1 › Teplizumab and β-Cell Function in Newly...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Hormones peptidiques › Hormones pancréatiques › Insulines › Peptide C › Teplizumab and β-Cell Function in Newly...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hypoglycémiants › Teplizumab and β-Cell Function in Newly...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Teplizumab and β-Cell Function in Newly...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Méthode en double aveugle › Teplizumab and β-Cell Function in Newly...