Phase 3
N=179
Trial of Otelixizumab for Adolescents and Adults With Newly Diagnosed Type 1 Diabetes Mellitus (Autoimmune): DEFEND-2
Diabetes Mellitus, Type 1
Bottom Line
View on ClinicalTrials.gov: NCT01123083 ↗Enrolled (actual)
179
Serious AEs
8.4%
Results posted
Sep 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 — -0.14; -0.23 nanomoles per liter — p=0.051
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Otelixizumab (Biological); Placebo (Biological)
- Age
- Pediatric · 12+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Mar 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 |
-0.14; -0.23 | 0.051 |
| SECONDARY Change From Baseline in 2 Hour Mixed Meal-stimulated C-peptide AUC (Normalized for 120-minute Time Interval) at Week 12 and 6 Months |
0.05; -0.05; -0.04; -0.10 | 0.022 sig |
| SECONDARY Change From Baseline in Stimulated C-Peptide Mean AUC at Week 12, Month 6, 12 and 18 |
0.0519; -0.0472; -0.0455; -0.0945; -0.1236; -0.2331 | — |
| SECONDARY Number of Participants With Responder Status |
19; 42; 11; 26; 10; 23 | 0.912 |
| SECONDARY Change From Baseline in Mean Daily Insulin Use Over 7 Consecutive Days During the 2 Weeks Prior to the Assessment |
-0.04; -0.08; 0.01; -0.04; 0.01; 0.05 | 0.210 |
| SECONDARY Change From Baseline in HbA1c Levels Over 7 Consecutive Days During the 2 Weeks Prior to the Assessment |
-0.82; -1.01; -0.65; -0.65; -0.61; -0.47 | 0.582 |
| SECONDARY Average Number of Severe Hypoglycemic Events and Documented Symptomatic Hypoglycemic Events From Baseline to Month 12 |
33; 11; 429; 690; 822; 1300 | — |
| SECONDARY Percentage of Participants With Change From Baseline in Severe Hypoglycemic Events and Documented Symptomatic Hypoglycemic Events at Month 12 |
11.5; 5.9; 36.1; 28.8; 45.9; 43.2 | — |
| SECONDARY Composite Rank Sum: HbA1c and Exogenous Insulin Use at 6 and 12 Months |
119; 110; 96; 110 | 0.452 |
| SECONDARY Composite Rank Sum: C-Peptide AUC, HbA1c and Exogenous Insulin Use at 6 and 12 Months |
206; 186; 180; 170 | 0.123 |
Summary
DEFEND-2 is a Phase 3 confirmatory study for the Phase 3 DEFEND-1 study. The study objective is to find out if an 8-day series of otelixizumab infusions leads to greater improvement in insulin secretion as compared with placebo. 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 standard of care treatments.
Eligibility Criteria
Inclusion Criteria
- Ages 12-17
- 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. In Canada, has to be using insulin at the time of dosing.
- 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 (NCT01123083). 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.