Rapid Onset and Sustained Efficacy of Onfasprodil (MIJ821), a Novel NR2B Negative Allosteric Modulator, in Patients With Treatment-Resistant Depression
Bibliographic record
Abstract
Onfasprodil (MIJ821) is a highly potent and novel selective NR2B subunit negative allosteric modulator. This phase 2, randomized, placebo-controlled, proof-of-concept study evaluated efficacy and safety of onfasprodil in patients with treatment-resistant major depression (TRD). Adults with TRD who did not respond to ≥2 antidepressants were randomized (3:3:3:3:6:4) to receive a 40-minute intravenous infusion of onfasprodil 0.16 mg/kg weekly (n = 11), onfasprodil 0.16 mg/kg biweekly (n = 10), onfasprodil 0.32 mg/kg weekly (n = 10), onfasprodil 0.32 mg/kg biweekly (n = 9), placebo weekly (n=20), or ketamine 0.5 mg/kg weekly (n= 10) for 6 weeks. Primary end point was change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score at 24 hours. Secondary end points were change in MADRS score at 48 hours and at final follow-up at 6 weeks. Safety and tolerability were assessed during the study. = .1133) for pooled 0.32 mg/kg groups. The commonest treatment-emergent adverse events in the onfasprodil groups were dizziness (14.3%), transient amnesia (14.3%), and somnolence (11.4%). It had overall a good safety profile and was well tolerated. Onfasprodil appeared to be effective and well-tolerated across all dosing regimens in patients with TRD and demonstrated rapid onset of action (24 hours) with evidence of antidepressant effects to be maintained at Week 6, particularly for the lower-dose group. ClinicalTrials.gov identifier: NCT03756129.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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 source (direct Gemma or distilled Codex), 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".