PHYOX8: Nedosiran in Pediatric Patients with Primary Hyperoxaluria
Bibliographic record
Abstract
Background: Primary hyperoxaluria type 1 (PH1) is a genetic disorder causing excessive hepatic oxalate production, leading to kidney stones and nephrocalcinosis, often starting in childhood. If untreated, it can harm kidneys and other organs. Nedosiran is an RNAi therapy that inhibits hepatic lactate dehydrogenase (LDH; LDHA gene), reducing oxalate production. It is administered monthly via subcutaneous injection and is FDA-approved for PH1 patients aged ≥2 years with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2. Methods: PHYOX8 (NCT05001269) is a phase 2 multi-dose, open label clinical trial assessing the efficacy and safety of nedosiran in reducing urinary oxalate (Uox) excretion in pediatric participants (birth to 11 years) with PH and eGFR ≥30mL/min/1.73m2. Reported here are the results from the full cohort of 20 pediatric patients (aged 10 months to 11 years) with PH1 who received nedosiran once-monthly for 6 months in PHYOX8 (Feb 2022 to Feb 2025). The study population was distributed in three age groups: <2 years (n=3), between 2 to <6 years (n=9), and between 6 to 11 years (n=8). The overall mean age was 4.98 years (SD=2.777). Participants were predominantly male (n=14; 70%). Results: As primary endpoint of this study, a significant reduction in mean Uox:creatinine (Cr) ratio was observed in patients receiving nedosiran treatment. The least squares (LS) mean percentage change in the mean Uox:Cr ratio from baseline to month 6 was -66.204 % (95% CI: -81.282, -51.126). At month 6, 9 (45%) participants had normal mean Uox:Cr ratios (i.e. ≤1.0x upper limit of normal [ULN]), while 15 (75%) had ratios ≤1.5x ULN. The mean eGFR remained stable. Consistent with previous reported data, nedosiran was well tolerated. Seven participants (25.9%) had treatment-related adverse events (AEs; unrelated to nedosiran) that did not lead to discontinuation. No serious treatment-related AEs were reported. Injection-site reaction and muscle pain or weakness were observed in one participant each (3.7%). These events, along with kidney stone events, are protocol-defined adverse events of special interest (AESI). Conclusion: Nedosiran was well-tolerated in children aged from 10 months to 11 years with PH1. Nedosiran treatment resulted in a notable reduction of mean Uox:Cr in this population.
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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) | 0.000 | 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 | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".