Nedosiran in Pediatric Patients with PH1 (PHYOX8)
Bibliographic record
Abstract
Background: Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder leading to excessive hepatic production of oxalate, which can cause deposition of calcium oxalate crystals in the form of recurring kidney stones and nephrocalcinosis.PH1 often presents in childhood and, if left untreated, may result in progressive damage to kidneys and other organs. Nedosiran is a synthetic RNA interference (RNAi) agent designed to selectively reduce hepatic LDH (encoded by the LDHA gene) to decrease oxalate burden. Nedosiran is administered as a monthly subcutaneous injection and is FDA-approved for patients with PH1 (≥9 years of age; eGFR ≥30mL/min/1.73 m2). Methods: PHYOX8 (NCT05001269) is a phase 2 clinical trial evaluating the efficacy and safety of nedosiran in lowering urinary oxalate (Uox) excretion in pediatric participants (birth to 11 years) with PH1 and eGFR ≥30mL/min/1.73m2. Reported here are the results of 15 pediatric patients (2 to 10 years of age) with PH1 who received nedosiran once monthly for 6 months in PHYOX8 (Feb 2022 to Aug 2023). Results: A substantial reduction in spot Uox:creatinine (cr) ratio was observed in patients treated with nedosiran (Figure 1): the least squares (LS) mean of percent change in spot Uox:cr ratio from baseline to month 6 was -64.1% (95% CI: -83.8, -44.4). At the month 6 visit, 6 (40%) participants had normal (i.e. ≤ULN) spot Uox:cr ratios, whereas 11 (73%) had Uox:cr ratios ≤1.5 x ULN. Further, there was a mean reduction of 10% in the surface area of kidney stones from baseline to month 6. The mean eGFR remained stable. Nedosiran was well tolerated; 3 participants experienced treatment-related AEs that did not result in discontinuation of treatment or from the study. There were no treatment-related serious AEs. One participant (6.7%) experienced an injection-site reaction. No muscle pain or weakness was observed. Conclusion: Nedosiran appeared to be safe and well-tolerated in children aged ≥2 years with PH1. Nedosiran treatment led to a substantial reduction of spot Uox:cr in this population. Funding: Commercial Support - Dicerna Pharmaceuticals, a Novo Nordisk Company
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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 | 0.000 | 0.000 |
| 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".