Randomized Clinical Trial on the Long-Term Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1
Introduction: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by hepatic overproduction of oxalate, leading to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. In the 6-month double-blind period (DBP) of ILLUMINATE-A, a phase 3, randomized, placebo-controll...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-03-01
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| Series: | Kidney International Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024921015916 |
| _version_ | 1818488490436853760 |
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| author | Sally A. Hulton Jaap W. Groothoff Yaacov Frishberg Michael J. Koren J. Scott Overcash Anne-Laure Sellier-Leclerc Hadas Shasha-Lavsky Jeffrey M. Saland Wesley Hayes Daniella Magen Shabbir H. Moochhala Martin Coenen Eva Simkova Sander F. Garrelfs David J. Sas Kristin A. Meliambro Taylor Ngo Marianne T. Sweetser Bahru A. Habtemariam John M. Gansner Tracy L. McGregor John C. Lieske |
| author_facet | Sally A. Hulton Jaap W. Groothoff Yaacov Frishberg Michael J. Koren J. Scott Overcash Anne-Laure Sellier-Leclerc Hadas Shasha-Lavsky Jeffrey M. Saland Wesley Hayes Daniella Magen Shabbir H. Moochhala Martin Coenen Eva Simkova Sander F. Garrelfs David J. Sas Kristin A. Meliambro Taylor Ngo Marianne T. Sweetser Bahru A. Habtemariam John M. Gansner Tracy L. McGregor John C. Lieske |
| author_sort | Sally A. Hulton |
| collection | DOAJ |
| description | Introduction: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by hepatic overproduction of oxalate, leading to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. In the 6-month double-blind period (DBP) of ILLUMINATE-A, a phase 3, randomized, placebo-controlled trial in patients with PH1 ≥6 years old, treatment with lumasiran, an RNA interference therapeutic, led to substantial reductions in urinary oxalate (UOx) levels. Methods: We report data to month 12 in the extension period (EP) of ILLUMINATE-A, including patients who continued lumasiran (lumasiran/lumasiran) or crossed over from placebo to lumasiran (placebo/lumasiran). Results: In the lumasiran/lumasiran group (n = 24), the reduction in 24-hour UOx level was sustained to month 12 (mean reduction from baseline, 66.9% at month 6; 64.1% at month 12). The placebo/lumasiran group (n = 13) had a similar time course and magnitude of 24-hour UOx reduction (mean reduction, 57.3%) after 6 months of lumasiran. Kidney stone event rates seemed to be lower after 6 months of lumasiran in both groups compared with the 12 months before consent, and this reduction was maintained at month 12 in the lumasiran/lumasiran group. At study start, 71% of patients in the lumasiran/lumasiran group and 92% in the placebo/lumasiran group had nephrocalcinosis. Nephrocalcinosis grade improved after 6 months of lumasiran in the lumasiran/lumasiran and placebo/lumasiran groups (13% and 8% of patients, respectively). After an additional 6 months of lumasiran, 46% of patients had improvement in nephrocalcinosis grade within the lumasiran/lumasiran group. Estimated glomerular filtration rate (eGFR) remained stable during the course of lumasiran treatment. The most common adverse events (AEs) related to lumasiran were mild, transient injection-site reactions (ISRs). Conclusion: Long-term lumasiran treatment enabled sustained lowering of UOx levels with acceptable safety and encouraging results on clinical outcomes. |
| first_indexed | 2024-12-10T16:51:41Z |
| format | Article |
| id | doaj.art-d1c32da830c840358e1a339f45ee8a45 |
| institution | Directory Open Access Journal |
| issn | 2468-0249 |
| language | English |
| last_indexed | 2024-12-10T16:51:41Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj.art-d1c32da830c840358e1a339f45ee8a452022-12-22T01:40:53ZengElsevierKidney International Reports2468-02492022-03-0173494506Randomized Clinical Trial on the Long-Term Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1Sally A. Hulton0Jaap W. Groothoff1Yaacov Frishberg2Michael J. Koren3J. Scott Overcash4Anne-Laure Sellier-Leclerc5Hadas Shasha-Lavsky6Jeffrey M. Saland7Wesley Hayes8Daniella Magen9Shabbir H. Moochhala10Martin Coenen11Eva Simkova12Sander F. Garrelfs13David J. Sas14Kristin A. Meliambro15Taylor Ngo16Marianne T. Sweetser17Bahru A. Habtemariam18John M. Gansner19Tracy L. McGregor20John C. Lieske21Department of Nephrology, Birmingham Women’s and Children’s Hospital, Birmingham, UK; Correspondence: Sally-Anne Hulton, Department of Nephrology, Birmingham Women’s and Children's Hospital NHS Foundation Trust, Steelhouse Lane, Birmingham B4 6NH, UK.Department of Pediatric Nephrology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDivision of Pediatric Nephrology, Shaare Zedek Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelJacksonville Center for Clinical Research, Jacksonville, Florida, USAVelocity Clinical Research, San Diego, California, USAHôpital Femme Mère Enfant and Centre d’Investigation Clinique Institut National de la Santé et de la Recherche Médicale, Hospices Civils de Lyon, ERKnet, Bron, FrancePediatric Nephrology Unit, Galilee Medical Center and Azrieli Faculty of Medicine, Bar-Ilan University, Nahariya, IsraelIcahn School of Medicine at Mount Sinai, New York, New York, USADepartment of Pediatric Nephrology, Great Ormond Street Hospital, London, UKPediatric Nephrology Institute, Rambam Health Care Campus, Haifa, IsraelUCL Department of Renal Medicine, Royal Free Hospital, London, UKDepartment of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, GermanyAl Jalila Children’s Hospital, Dubai, United Arabs EmiratesDepartment of Pediatric Nephrology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDivision of Pediatric Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USAIcahn School of Medicine at Mount Sinai, New York, New York, USAAlnylam Pharmaceuticals, Cambridge, Massachusetts, USAAlnylam Pharmaceuticals, Cambridge, Massachusetts, USAAlnylam Pharmaceuticals, Cambridge, Massachusetts, USAAlnylam Pharmaceuticals, Cambridge, Massachusetts, USAAlnylam Pharmaceuticals, Cambridge, Massachusetts, USADivision of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USAIntroduction: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by hepatic overproduction of oxalate, leading to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. In the 6-month double-blind period (DBP) of ILLUMINATE-A, a phase 3, randomized, placebo-controlled trial in patients with PH1 ≥6 years old, treatment with lumasiran, an RNA interference therapeutic, led to substantial reductions in urinary oxalate (UOx) levels. Methods: We report data to month 12 in the extension period (EP) of ILLUMINATE-A, including patients who continued lumasiran (lumasiran/lumasiran) or crossed over from placebo to lumasiran (placebo/lumasiran). Results: In the lumasiran/lumasiran group (n = 24), the reduction in 24-hour UOx level was sustained to month 12 (mean reduction from baseline, 66.9% at month 6; 64.1% at month 12). The placebo/lumasiran group (n = 13) had a similar time course and magnitude of 24-hour UOx reduction (mean reduction, 57.3%) after 6 months of lumasiran. Kidney stone event rates seemed to be lower after 6 months of lumasiran in both groups compared with the 12 months before consent, and this reduction was maintained at month 12 in the lumasiran/lumasiran group. At study start, 71% of patients in the lumasiran/lumasiran group and 92% in the placebo/lumasiran group had nephrocalcinosis. Nephrocalcinosis grade improved after 6 months of lumasiran in the lumasiran/lumasiran and placebo/lumasiran groups (13% and 8% of patients, respectively). After an additional 6 months of lumasiran, 46% of patients had improvement in nephrocalcinosis grade within the lumasiran/lumasiran group. Estimated glomerular filtration rate (eGFR) remained stable during the course of lumasiran treatment. The most common adverse events (AEs) related to lumasiran were mild, transient injection-site reactions (ISRs). Conclusion: Long-term lumasiran treatment enabled sustained lowering of UOx levels with acceptable safety and encouraging results on clinical outcomes.http://www.sciencedirect.com/science/article/pii/S2468024921015916lumasirannephrocalcinosisphase 3 clinical trialprimary hyperoxaluria type 1RNA interferenceurinary oxalate |
| spellingShingle | Sally A. Hulton Jaap W. Groothoff Yaacov Frishberg Michael J. Koren J. Scott Overcash Anne-Laure Sellier-Leclerc Hadas Shasha-Lavsky Jeffrey M. Saland Wesley Hayes Daniella Magen Shabbir H. Moochhala Martin Coenen Eva Simkova Sander F. Garrelfs David J. Sas Kristin A. Meliambro Taylor Ngo Marianne T. Sweetser Bahru A. Habtemariam John M. Gansner Tracy L. McGregor John C. Lieske Randomized Clinical Trial on the Long-Term Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1 Kidney International Reports lumasiran nephrocalcinosis phase 3 clinical trial primary hyperoxaluria type 1 RNA interference urinary oxalate |
| title | Randomized Clinical Trial on the Long-Term Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1 |
| title_full | Randomized Clinical Trial on the Long-Term Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1 |
| title_fullStr | Randomized Clinical Trial on the Long-Term Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1 |
| title_full_unstemmed | Randomized Clinical Trial on the Long-Term Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1 |
| title_short | Randomized Clinical Trial on the Long-Term Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1 |
| title_sort | randomized clinical trial on the long term efficacy and safety of lumasiran in patients with primary hyperoxaluria type 1 |
| topic | lumasiran nephrocalcinosis phase 3 clinical trial primary hyperoxaluria type 1 RNA interference urinary oxalate |
| url | http://www.sciencedirect.com/science/article/pii/S2468024921015916 |
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