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Clinical evidence for the safety of GAD65 immunomodulation in adult-onset autoimmune diabetes.

Author:
  • Carl-David Agardh
  • Corrado M Cilio
  • ÅsaLinda Lethagen
  • Kristian Lynch
  • R David G Leslie
  • Mats Palmér
  • Robert A Harris
  • John A Robertson
  • Åke Lernmark
Publishing year: 2005
Language: English
Pages: 238-246
Publication/Series: Journal of Diabetes and its Complications1992-01-01+01:00
Volume: 19
Issue: 4
Document type: Journal article
Publisher: Elsevier

Abstract english

The purpose of this Phase II study was to evaluate if alum-formulated human recombinant GAD65 is safe and does not compromise beta cell function. The study was conducted as a randomized, double blind, placebo-controlled, dose-escalation clinical trial in a total of 47 Latent Autoimmune Diabetes in Adults (LADA) patients who received either placebo or 4, 20, 100, or 500 μg Diamyd subcutaneously at Weeks 1 and 4. Safety evaluations, including neurology, beta cell function tests, diabetes status assessment, hematology, biochemistry, and cellular and humoral immunological markers, were repeatedly assessed over 24 weeks. None of the patients had significant study-related adverse events (AE). Fasting c-peptide levels at 24 weeks were increased compared with placebo (P=.0015) in the 20 μg but not in the other dose groups. In addition, both fasting (P=.0081) and stimulated (P=.0236) c-peptide levels increased from baseline to 24 weeks in the 20 μg dose group. GADA log levels clearly increased (P=.0002) in response to 500 μg Diamyd. The CD4+CD25+/CD4+CD25− cell ratio increased (P=.0128) at 24 weeks in the 20 μg group. No sudden increase in HbA1c or plasma glucose or decrease in beta cell function was observed in any of the dose groups. These positive findings for clinical safety further support the clinical development of Diamyd as a therapeutic to prevent autoimmune diabetes.

Keywords

  • Endocrinology and Diabetes
  • Safety
  • Adult-onset autoimmune diabetes
  • GAD65 immunomodulation

Other

Published
  • Genomics, Diabetes and Endocrinology
  • Diabetes and Celiac Unit
  • ISSN: 1873-460X
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79

60:11:015

Jan Waldenströms gata 35, Malmö

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00