No Effect of the Altered Peptide Ligand NBI-6024 on β-Cell Residual Function and Insulin Needs in New-Onset Type 1 Diabetes
- Markus Walter, MD1,
- Areti Philotheou, MD2,
- François Bonnici, MD2,
- Anette-G. Ziegler, MD1,
- Roland Jimenez, BS3 and
- on behalf of the NBI-6024 Study Group*
- 1Diabetes Research Institute, Forschergruppe Diabetes e.V., Munich, Germany;
- 2Diabetes Clinical Trials Unit, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa, and
- 3Clinical Development, Neurocrine Biosciences, San Diego, California.
- Corresponding author: Anette-G. Ziegler, anziegler{at}lrz.uni-muenchen.de.
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 β-cell function in patients with recently diagnosed type 1 diabetes.
RESEARCH DESIGN AND 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 ∼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 β-cell function.
Footnotes
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↵*A complete list of the NBI-6024 Study Group can be found in the appendix.
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Clinical trial reg. no. NCT00873561, clinicaltrials.gov.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received April 6, 2009.
- Accepted August 3, 2009.
- © 2009 by the American Diabetes Association.
