A phase I study to evaluate the safety, tolerance and pharmacokinetics of anti‐Shiga toxin hyperimmune equine F (ab′)<sub>2</sub> fragments in healthy volunteers
Bibliographic record
Abstract
Aims Shiga toxin‐producing Escherichia coli‐haemolytic uraemic syndrome (STEC‐HUS) is considered a toxaemic disorder in which early intervention with neutralizing antibodies may have therapeutic benefits. INM004, composed of F (ab′)2 fragments from equine immunoglobulins, neutralizes Stx1/Stx2, potentially preventing the onset of HUS. Methods A single‐centre, randomized, phase 1, single‐blind, placebo‐controlled clinical trial to evaluate INM004 safety, tolerance and pharmacokinetics (PK) in healthy adult volunteers, was conducted; in stage I, eight subjects were divided in two cohorts (n = 4) to receive a single INM004 dose of 2 or 4 mg kg−1, or placebo (INM004:placebo ratio of 3:1). In stage II, six subjects received three INM004 doses of 4 mg kg−1 repeated every 24 h, or placebo (INM004:placebo ratio of 5:1). Results Eight subjects (57.1%) experienced mild treatment‐emergent adverse events (TEAEs); most frequent were rhinitis, headache and flushing, resolved within 24 h without changes in treatment or additional intervention. No serious AEs were reported. Peak concentrations of INM004 occurred within 2 h after infusion, with median Cmax values of 45.1 and 77.7 μg mL−1 for 2 and 4 mg kg−1, respectively. The serum concentration of INM004 declined in a biphasic manner (t1/2 range 30.7–52.9 h). Systemic exposures increased with each subsequent dose in a dose‐proportional manner, exhibiting accumulation. Geometric median Cmax and AUC values were 149 and 10 300 μg h mL−1, respectively, in the repeated dose regimen. Additionally, samples from subjects that received INM004 at 2 mg kg−1 showed neutralizing capacity against Stx1 and Stx2 in in vitro assays. Conclusions The results obtained in this first‐in‐human study support progression into the phase 2 trial in children with HUS.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".