title: No effect of the altered peptide ligand NBI-6024 on beta-cell residual function and insulin needs in new-onset type 1 diabetes.
abstract: OBJECTIVE
  This randomized, four-arm, placebo-controlled, dose-ranging phase 2 trial was conducted to determine whether repeated subcutaneous injections of the altered peptide ligand, NBI-6024, designed to inhibit autoreactive T-cells, improves beta-cell function in patients with recently diagnosed type 1 diabetes.
  
  
  METHODS
  A total of 188 patients, aged 10-35 years, with recently diagnosed type 1 diabetes were randomly assigned for a treatment consisting of the subcutaneous administration of placebo or 1, 0.5, or 0.1 mg NBI-6024 at baseline, weeks 2 and 4, and then monthly until month 24. Fasting, peak, and area under the curve (AUC) C-peptide concentrations during a 2-h mixed-meal tolerance test were measured at 3-month intervals during treatment. Immune function parameters (islet antibodies and CD4 and CD8 T-cells) were also studied.
  
  
  RESULTS
  The mean peak C-peptide concentration at 24 months after study entry showed no significant difference between the groups treated with 0.1 mg (0.59 pmol/ml), 0.5 mg (0.57 pmol/ml), and 1.0 mg NBI-6024 (0.48 pmol/ml) and the placebo group (0.54 pmol/ml). Fasting, stimulated peak, and AUC C-peptide concentrations declined linearly in all groups by approximately 60% over the 24-month treatment period. The average daily insulin needs at month 24 were also comparable between the four groups. No treatment-related changes in islet antibodies and T cell numbers were observed.
  
  
  CONCLUSIONS
  Treatment with altered peptide ligand NBI-6024 at repeated doses of 0.1, 0.5, or 1.0 mg did not improve or maintain beta-cell function.
authors.affiliation: Diabetes Research Institute, Forschergruppe Diabetes e.V., Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Walter
authors.forename: Areti
authors.initials: A
authors.lastname: Philotheou
authors.forename: François
authors.initials: F
authors.lastname: Bonnici
authors.forename: Anette-G
authors.initials: AG
authors.lastname: Ziegler
authors.forename: Roland
authors.initials: R
authors.lastname: Jimenez
mesh_terms: D000293:Adolescent; D000328:Adult; D002096:C-Peptide / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D010919:Placebos; D055815:Young Adult
chemical_list: D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; C460599:NBI6024; D010446:Peptide Fragments; D010919:Placebos
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