Advanced

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

Agardh, Carl-David LU ; Cilio, Corrado M; Lethagen, ÅsaLinda LU ; Lynch, Kristian LU ; Leslie, R David G; Palmér, Mats; Harris, Robert A; Robertson, John A and Lernmark, Åke LU (2005) In Journal of Diabetes and its Complications 19(4). p.238-246
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Safety, Adult-onset autoimmune diabetes, GAD65 immunomodulation
in
Journal of Diabetes and its Complications
volume
19
issue
4
pages
238 - 246
publisher
Elsevier
external identifiers
  • wos:000230771500009
  • scopus:21344461521
ISSN
1873-460X
DOI
10.1016/j.jdiacomp.2004.12.003
language
English
LU publication?
yes
id
5c0ce474-560a-40b5-9692-405c1d88a6cb (old id 142393)
date added to LUP
2007-07-09 13:40:57
date last changed
2017-10-22 04:46:58
@article{5c0ce474-560a-40b5-9692-405c1d88a6cb,
  abstract     = {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.},
  author       = {Agardh, Carl-David and Cilio, Corrado M and Lethagen, ÅsaLinda and Lynch, Kristian and Leslie, R David G and Palmér, Mats and Harris, Robert A and Robertson, John A and Lernmark, Åke},
  issn         = {1873-460X},
  keyword      = {Safety,Adult-onset autoimmune diabetes,GAD65 immunomodulation},
  language     = {eng},
  number       = {4},
  pages        = {238--246},
  publisher    = {Elsevier},
  series       = {Journal of Diabetes and its Complications},
  title        = {Clinical evidence for the safety of GAD65 immunomodulation in adult-onset autoimmune diabetes.},
  url          = {http://dx.doi.org/10.1016/j.jdiacomp.2004.12.003},
  volume       = {19},
  year         = {2005},
}