Final 60-Month Efficacy, Safety, and Kidney Stone Outcomes of a Phase 3 Trial of Lumasiran for Primary Hyperoxaluria Type 1 in Infants and Young Children
Rattachement africain : us, il, gb, fr. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Background: Primary hyperoxaluria type 1 (PH1) is a genetic disease of oxalate overproduction leading to urolithiasis, nephrocalcinosis (NC), and systemic oxalosis. Lumasiran is the first liver-directed RNA interference therapeutic for PH1 administered to infants and children age ≤6 years. We present final efficacy and safety results through Month (M) 60 of ILLUMINATE-B (NCT03905694), including outcomes in patients (pts) who had kidney stone events (KSEs). Methods: This Phase 3, open-label, single-arm study enrolled pts with PH1 age <6 years, eGFR >45 mL/min/1.73m2 (age ≥12M) or normal serum creatinine (age <12M), and urinary oxalate:creatinine ratio (UOx:Cr) > the upper limit of normal. Weight-based lumasiran was administered subcutaneously. Results are summarized descriptively. Results: All pts (N=18) completed the 6M primary analysis, entered the 54M extension, and completed the study at M60. From baseline (BL) to M60, mean (SEM) change in spot UOx:Cr was −74% (4.2), and in plasma oxalate (POx), −25% (12.8). Annual rate of change (slope) in mean eGFR was +0.26 (SEM 0.8) mL/min/1.73m2/y. The most common lumasiran-related adverse events were mild, transient injection site reactions (n=3 pts [17%]). In 14 pts with NC at BL, NC grade (range 0/0-3/3) was improved at M60 in 12 (86%); none worsened. The 4 pts without NC at BL remained NC-free at M60. In the trial, 9 KSEs were reported in only 4 pts, whose spot UOx:Cr change ranged from −74.5% to −93.4% at M60. Two of the pts had 1 KSE each; 1 had BL grade 1/1 NC and improved to complete resolution (0/0) at M60, and 1 had no NC at BL or at M60. The other 2 pts had >1 KSE, and both had grade 3/3 NC at BL; at M60, 1 pt (5 KSEs) had complete NC resolution and the other (2 KSEs) had no change in NC grade. Conclusion: Infants and young children with PH1 had sustained UOx and POx reductions over 60M of lumasiran treatment in ILLUMINATE-B, with stable eGFR and acceptable safety. NC grade improved in most pts, and most did not have KSEs. The 4 pts with KSEs had UOx reductions and changes in NC grade consistent with those of other trial pts. Funding: Commercial Support - Alnylam Pharmaceuticals
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Final 60-Month Efficacy, Safety, and Kidney Stone Outcomes of a Phase 3 Trial of Lumasiran for Primary Hyperoxaluria Type 1 in Infants and Young Children
- Date Crossref
- 01/10/2025
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Mayo Clinic pays non établi dans la noticeÉtablissement de santé
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Texas Children's Hospital pays non établi dans la noticeOrganisme public
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Shaare Zedek Medical Center pays non établi dans la noticeÉtablissement de santé
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Great Ormond Street Hospital pays non établi dans la noticeÉtablissement de santé
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University College London pays non établi dans la noticeUniversité ou école supérieure
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Western Galilee Hospital pays non établi dans la noticeÉtablissement de santé
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Hôpital Femme Mère Enfant pays non établi dans la noticeÉtablissement de santé
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Assistance Publique – Hôpitaux de Paris pays non établi dans la noticeÉtablissement de santé
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Hôpital Robert-Debré pays non établi dans la noticeÉtablissement de santé
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Alnylam Pharmaceuticals (United States) pays non établi dans la noticeEntreprise
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Galilee Medical Center pays non établi dans la noticeÉtablissement de santé
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Robert Debré Hospital pays non établi dans la noticeÉtablissement de santé
Mayo Clinic, Texas Children's Hospital et Shaare Zedek Medical Center, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.