Low-Dose Otelixizumab Anti-CD3 Monoclonal Antibody DEFEND-1 Study: Results of the Randomized Phase III Study in Recent-Onset Human Type 1 Diabetes
Bibliographic record
Abstract
OBJECTIVE: Previous studies demonstrated that the anti-CD3 monoclonal antibody otelixizumab, administered at a total dose of 48-64 mg, can slow the loss of C-peptide in recent-onset type 1 diabetes patients, with frequent reactivation of Epstein Barr virus (EBV). The DEFEND-1 (Durable Response Therapy Evaluation for Early or New-Onset Type 1 Diabetes) trial was designed to test whether a lower dose of otelixizumab could preserve C-peptide secretion in new-onset type 1 diabetes patients. RESEARCH DESIGN AND METHODS: A multicenter, randomized, placebo-controlled trial was performed in sites in the U.S., Canada, and Europe. Two hundred eighty-one patients were randomized to treatment with 3.1 mg otelixizumab administered over 8 days or placebo. The primary end point of the study was the change in C-peptide area under the curve (AUC) from a 2-h mixed-meal tolerance test at month 12. RESULTS: The change in 2-h C-peptide AUC was not different between placebo-treated patients and otelixizumab-treated patients (-0.20 vs. -0.22 nmol/L, P = 0.81). Secondary end points, including HbA1c, glucose variability, and insulin dose, were also not statistically different between the two groups. More patients in the otelixizumab group than in the placebo group experienced adverse events, mostly grade 1 or grade 2. There was no EBV reactivation (viral load >10,000 copies/10(6) peripheral blood mononuclear cells) in the otelixizumab group, in contrast with previously published studies at higher doses of otelixizumab. CONCLUSIONS: Otelixizumab was well tolerated in patients with recent-onset type 1 diabetes at a total dose of 3.1 mg, but did not achieve preservation of levels of C-peptide or other markers of metabolic control.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".