Phase 3
N=272
Trial of Otelixizumab for Adults With Newly Diagnosed Type 1 Diabetes Mellitus (Autoimmune): DEFEND-1
Diabetes Mellitus, Type 1
Bottom Line
View on ClinicalTrials.gov: NCT00678886 ↗Enrolled (actual)
272
Serious AEs
7.7%
Results posted
Oct 2017
Primary outcome: Primary: Change From Baseline in 2-hour Mixed Meal Stimulated C-peptide Area Under Curve [AUC] (Normalized for 120-minute Time Interval) at Month 12 — -0.21; -0.21 nanomoles per liter — p=0.813
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- otelixizumab infusion plus physician determined standard of care (Biological); placebo infusion plus physician determined standard of care (Biological)
- Age
- Pediatric, Adult · 12+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Jan 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in 2-hour Mixed Meal Stimulated C-peptide Area Under Curve [AUC] (Normalized for 120-minute Time Interval) at Month 12 |
-0.21; -0.21 | 0.813 |
| SECONDARY Number of Participants Who Were Responders for (Glycosylated Hemoglobin) HbA1c/Insulin Use Response at Week 12 and Months 6 and 12 |
45; 85; 42; 74; 34; 56 | 0.737 |
| SECONDARY Mean Daily Insulin Use at Week 12 and Months 6 and 12. |
0.34; 0.31; 0.36; 0.36; 0.42; 0.39 | 0.281 |
| SECONDARY HbA1c Level at Week 12 and Months 6 and 12 |
6.83; 7.02; 6.60; 6.77; 6.45; 6.54 | 0.289 |
| SECONDARY Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12 |
2; 5; 3092; 6322; 4718; 9962 | — |
| SECONDARY Number of Participants With Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12 |
2; 4; 78; 163; 10; 13 | — |
| SECONDARY Number of Hypoglycemic Excursions (<=70 mg/dL) With Most Complete Glucose at Week 12 and Months 6 and 12. |
2.3; 2.8; 3.0; 2.9; 2.9; 3.2 | — |
| SECONDARY Magnitude of Greatest Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12. |
9.4; 10.8; 11.9; 10.6; 11.2; 11.0 | — |
| SECONDARY Number of Participants With Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12 |
72; 127; 57; 121; 56; 111 | — |
| SECONDARY Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12. |
34.0; 32.9; 20.5; 19.9; 5.7; 5.6 | — |
| SECONDARY Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12. |
158.3; 158.4; 128.3; 128.4; 65.7; 65.7 | — |
| SECONDARY Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12 |
90; 177; 90; 177; 65; 130 | — |
| SECONDARY Change From Baseline in Average Daily Risk Range (ADRR) at Week 12 and Months 6 and 12. |
-0.41; 0.71; 2.03; 2.86; 3.29; 4.22 | 0.540 |
| SECONDARY Composite Rank Summary for HbA1c and Exogenous Insulin Use at Month 6 and Month 12 |
238; 247; 245; 244 | 0.957 |
| SECONDARY Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use at Month 6 and Month 12 |
365; 373; 360; 366 | 0.653 |
| SECONDARY Change From Baseline in Level of Cytokines Interleukin (IL-6), IL-10 and Tumor Necrosis Factor-alpha (TNF-a) at Day 1, Day 4, Day 8 |
0.76; 2.78; -0.13; 3.01; 0.45; 14.59 | — |
| SECONDARY Percent Change From Baseline in Circulating Peripheral Lymphocytes CD4+CD25+FoxP3+ T Cells and CD4+CD25hiFoxP3+ T Cells in Type 1 Diabetes Mellitus (TIDM) up to Month 12 |
118.8; 53.4; 94.4; 49.7; 113.2; 40.1 | — |
| SECONDARY Percent Change From Baseline in Cell-bound Otelixizumab on CD4+ T Cells at Day 1, Day 4, Day 8 |
125.1; 914.8; 174.3; 2719.8; 151.5; 471.5 | — |
| SECONDARY Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8 |
93.4; 90.9; 109.7; 50.2; 97.7; 59.0 | — |
| SECONDARY Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8 |
94.2; 91.1; 103.8; 70.8; 101.4; 61.0 | — |
Summary
The purpose of this study is to find out if an 8-day series of otelixizumab infusions leads to greater improvement in insulin secretion as compared with placebo infusion. Insulin secretion will be assessed using mixed meal-stimulated C-peptide.
Subjects will be assigned to receive either otelixizumab or placebo at a ratio of 2:1 (2/3 otelixizumab, 1/3 placebo). These study agents will be administered as an addition to insulin, diet, and other physician determined standard of care treatments.
DEFEND-1 is now closed to enrollment.
DEFEND-2 will begin early in 2010. It is very similar to DEFEND-1 and will again require subjects with new onset type 1 diabetes. Please check back here for more details.
In the meantime, established and new onset type 1 diabetes patients in North America are welcome to consider the TTEDD study:
http://www.clinicaltrials.gov/ct2/show/NCT00451321?term=TTEDD&rank=1
Eligibility Criteria
Inclusion Criteria
- Ages 12-45
- Diagnosis of diabetes mellitus, consistent with ADA criteria
- No more than 90 days between diagnosis and administration of study compounds
- Requires insulin for type 1 diabetes mellitus, or has required insulin at some time between diagnosis and administration of study compounds.
- Stimulated C-peptide level greater than 0.20 nmol/L and less than or equal to 3.50 nmol/L
- Positive for one or more of the autoantibodies typically associated with T1DM: antibody to glutamic acid decarboxylase (anti-GAD); antibody to protein tyrosine phosphatase-like protein (anti-IA-2); zinc transporter autoantibodies (ZNT8); insulin autoantibodies (IAA). A subject who is positive for insulin autoantibodies (IAA) and negative for the other autoantibodies will only be eligible if the subject has used insulin for less than 7 days total.
Exclusion Criteria
- Other, significant medical conditions based on the study doctor's evaluation
Data sourced from ClinicalTrials.gov (NCT00678886). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.