Evaluation of Changes in Laboratory Parameters from a Phase 2b Trial of Zasocitinib (TAK-279), an Oral, Selective TYK2 Inhibitor, in Patients with Moderate-to-Severe Plaque Psoriasis
Bibliographic record
Abstract
Background: Zasocitinib (TAK-279) is an oral, allosteric, and highly selective tyrosine kinase 2 inhibitor. In a recent phase 2b trial (NCT04999839), more patients with moderate-to-severe plaque psoriasis treated with zasocitinib 15 and 30 mg once daily achieved 75% improvement in the psoriasis area and severity index at Week 12 (primary endpoint) than those receiving placebo (PBO; p < 0.001). Here we report an assessment of laboratory parameters from this study. Methods: In this randomized, multicenter, double-blinded, PBO-controlled study, adults with moderate-to-severe plaque psoriasis were randomized 1:1:1:1:1 to receive oral zasocitinib (2, 5, 15 or 30 mg) or PBO once daily for 12 weeks. The safety analysis set included all patients who received ≥1 dose of the assigned study treatment. Laboratory parameters assessed throughout the trial included creatine kinase (CK), as well as hematologic (neutrophils, lymphocytes, hemoglobin, platelets), hepatic and renal (alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, estimated glomerular filtration rate), and lipid (cholesterol, triglycerides) parameters. Results: In total, 259 patients were included in the safety analysis set. Longitudinal changes in all laboratory parameters were generally similar in the PBO and zasocitinib groups. Mean values of most laboratory parameters remained within normal ranges during the study. There was no relationship between zasocitinib treatment and cytopenia. Some CK elevations were observed in both the PBO and zasocitinib groups, but most were transient or reversible and of Common Terminology Criteria for Adverse Events Grade 1 or 2 (Grade ≥2 events occurred in 2 [3.8%], 2 [4.0%], 6 [11.5%], 4 [7.5%] and 3 [5.8%] patients, in the PBO, and 2, 5, 15 and 30 mg groups, respectively), and were not associated with rhabdomyolysis. Mean triglyceride values were slightly higher than normal ranges at baseline and Week 12 in all treatment groups, including PBO, and were mainly asymptomatic, mild-to-moderate elevations. These changes were not accompanied by increases in serum cholesterol levels. Conclusion: Zasocitinib treatment did not result in adverse changes in hematologic, hepatic, renal or lipid parameters that are associated with Janus kinase (JAK) inhibition, suggesting that the mechanism of action of zasocitinib is distinct from that of JAK1/2/3 inhibition. Further phase 3 studies of zasocitinib in psoriasis are ongoing to confirm these observations (NCT06088043; NCT06108544).
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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 | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".