No Effect of the Altered-Peptide Ligand NBI-6024 on Beta Cell Residual Function and Insulin Needs in New-Onset Type 1 Diabetes

  1. Markus Walter, MD1,
  2. Areti Philotheou, MD2,
  3. François Bonnici, MD2,
  4. Anette-G. Ziegler, MD (anziegler{at}lrz.uni-muenchen.de)1,
  5. Roland Jimenez3 and
  6. on behalf of the NBI-6024 study group
  1. 1Diabetes Research Institute, Forschergruppe Diabetes e.V., Munich, Germany
  2. 2Diabetes Clinical Trials Unit, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
  3. 3Clinical Development/Neurocrine Biosciences, Inc

    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.

    Research, Design and Methods - One hundred eighty-eight patients, aged 10-35 years with recently diagnosed type 1 diabetes were randomized for a treatment consisting in the subcutaneous administration of placebo or 1 mg, 0.5 mg or 0.1 mg of NBI-6024 at baseline, week 2 and 4 and then monthly until month 24. Fasting, peak and AUC C-peptide concentrations during a 2-hour mixed meal tolerance test were measured at 3-monthly intervals during treatment. Immune function parameters (islet antibodies, CD4 and CD( T cells) were also studied.

    Results The mean peak C-peptide 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 values were also comparable between the 4 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.

    Footnotes

      • Received April 6, 2009.
      • Accepted August 3, 2009.

    This Article

    1. Diabetes Care
    1. Online-Only Appendix
    2. All Versions of this Article:
      1. dc09-0449v1
      2. 32/11/2036 most recent