Efficacy and safety of low-dose otelixizumab anti-CD3 monoclonal antibody in preserving C-peptide secretion in adolescent type 1 diabetes: DEFEND-2, a randomized, placebo-controlled, double-blind, multi-centre study

2013 ◽  
Vol 31 (4) ◽  
pp. 399-402 ◽  
Author(s):  
P. Ambery ◽  
T. W. Donner ◽  
N. Biswas ◽  
J. Donaldson ◽  
J. Parkin ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Type 1 Diabetes ◽  
Low Dose ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Multi Centre Study ◽  
C Peptide ◽  
Centre Study ◽  
Peptide Secretion

scholarly journals Study protocol: Minimum effective low dose: anti-human thymocyte globulin (MELD-ATG): phase II, dose ranging, efficacy study of antithymocyte globulin (ATG) within 6 weeks of diagnosis of type 1 diabetes

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e053669
Author(s):  
Charlotte S Wilhelm-Benartzi ◽  
Sarah E Miller ◽  
Sylvaine Bruggraber ◽  
Diane Picton ◽  
Mark Wilson ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Antithymocyte Globulin ◽  
Low Dose ◽  
Insulin Dose ◽  
Double Blind ◽  
C Peptide ◽  
Link Type ◽  
Significant Difference ◽  
Allocation Ratio

IntroductionType 1 diabetes (T1D) is a chronic autoimmune disease, characterised by progressive destruction of the insulin-producing β cells of the pancreas. One immunosuppressive agent that has recently shown promise in the treatment of new-onset T1D subjects aged 12–45 years is antithymocyte globulin (ATG), Thymoglobuline, encouraging further exploration in lower age groups.Methods and analysisMinimal effective low dose (MELD)-ATG is a phase 2, multicentre, randomised, double-blind, placebo-controlled, multiarm parallel-group trial in participants 5–25 years diagnosed with T1D within 3–9 weeks of planned treatment day 1. A total of 114 participants will be recruited sequentially into seven different cohorts with the first cohort of 30 participants being randomised to placebo, 2.5 mg/kg, 1.5 mg/kg, 0.5 mg/kg and 0.1 mg/kg ATG total dose in a 1:1:1:1:1 allocation ratio. The next six cohorts of 12–15 participants will be randomised to placebo, 2.5 mg/kg, and one or two selected middle ATG total doses in a 1:1:1:1 or 1:1:1 allocation ratio, as dependent on the number of middle doses, given intravenously over two consecutive days. The primary objective will be to determine the changes in stimulated C-peptide response over the first 2 hours of a mixed meal tolerance test at 12 months for 2.5 mg/kg ATG arm vs the placebo. Conditional on finding a significant difference at 2.5 mg/kg, a minimally effective dose will be sought. Secondary objectives include the determination of the effects of a particular ATG treatment dose on (1) stimulated C-peptide, (2) glycated haemoglobin, (3) daily insulin dose, (4) time in range by intermittent continuous glucose monitoring measures, (5) fasting and stimulated dry blood spot (DBS) C-peptide measurements.Ethics and disseminationMELD-ATG received first regulatory and ethical approvals in Belgium in September 2020 and from the German and UK regulators as of February 2021. The publication policy is set in the INNODIA (An innovative approach towards understanding and arresting Type 1 diabetes consortium) grant agreement (www.innodia.eu).Trial registration numberNCT03936634; Pre-results.

scholarly journals Comparison of proinsulin and C-peptide secretion in healthy versus long-standing type 1 diabetes mellitus cohorts: A pilot study

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0207065 ◽  
Author(s):  
Catherine A. Sullivan ◽  
Jose M. Cacicedo ◽  
Iniya Rajendran ◽  
Devin W. Steenkamp
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Pilot Study ◽  
Type 1 Diabetes Mellitus ◽  
C Peptide ◽  
Peptide Secretion

scholarly journals Low-Dose Otelixizumab Anti-CD3 Monoclonal Antibody DEFEND-1 Study: Results of the Randomized Phase III Study in Recent-Onset Human Type 1 Diabetes

Diabetes Care ◽  
2014 ◽  
Vol 37 (10) ◽  
pp. 2746-2754 ◽  
Author(s):  
Ronnie Aronson ◽  
Peter A. Gottlieb ◽  
Jens S. Christiansen ◽  
Thomas W. Donner ◽  
Emanuele Bosi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Type 1 Diabetes ◽  
Low Dose ◽  
Phase Iii ◽  
Recent Onset ◽  
Human Type ◽  
Study Results ◽  
Phase Iii Study ◽  
Human Type 1 Diabetes

scholarly journals A Single Course of Anti-CD3 Monoclonal Antibody hOKT3 1(Ala-Ala) Results in Improvement in C-Peptide Responses and Clinical Parameters for at Least 2 Years after Onset of Type 1 Diabetes

Diabetes ◽  
2005 ◽  
Vol 54 (6) ◽  
pp. 1763-1769 ◽  
Author(s):  
K. C. Herold ◽  
S. E. Gitelman ◽  
U. Masharani ◽  
W. Hagopian ◽  
B. Bisikirska ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Type 1 Diabetes ◽  
Clinical Parameters ◽  
C Peptide

scholarly journals Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications

Diabetes Care ◽  
2020 ◽  
pp. dc200567
Author(s):  
Anita Jeyam ◽  
Helen Colhoun ◽  
Stuart McGurnaghan ◽  
Luke Blackbourn ◽  
Timothy J. McDonald ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Microvascular Complications ◽  
Clinical Impact ◽  
C Peptide ◽  
Peptide Secretion

scholarly journals Low-dose ATG/GCSF in Established Type 1 Diabetes: A Five-Year Follow-up Report

2021 ◽  
Author(s):  
Andrea Lin ◽  
Jasmine A. Mack ◽  
Brittany Bruggeman ◽  
Laura M. Jacobsen ◽  
Amanda L. Posgai ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Low Dose ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Modeling Framework ◽  
C Peptide ◽  
Recent Onset

Previously, we demonstrated low-dose anti-thymocyte globulin (ATG) and granulocyte colony stimulating factor (GCSF) immunotherapy preserved C-peptide for two years in a pilot study of subjects with established type 1 diabetes (n=25). Herein, we evaluated the long-term outcomes of ATG/GCSF in study participants with five years of available follow-up data (n=15). The primary endpoint was area under the curve (AUC) C-peptide during a two-hour mixed-meal tolerance test (MMTT). After five years, there were no statistically significant differences in AUC C-peptide when comparing subjects who received ATG/GCSF versus placebo (p = 0.41). A modeling framework based on mean trajectories in C-peptide AUC over five years, accounting for differing trends between groups, was applied to re-categorize responders (n=9) and non-responders (n=7). ATG/GCSF reponders demonstrated nearly unchanged HbA1c over five years [mean (95% CI) adjusted change = 0.29% (-0.69%, 1.27%)], but the study was not powered for comparisons against non-responders 1.75% (-0.57%, 4.06%) and placebo 1.44% (0.21%, 2.66%). These data underscore the importance of long-term follow up in previous and ongoing phase 2 trials of low-dose ATG in recent-onset type 1 diabetes.

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