dc.contributor.author | Suhr, Ole B | |
dc.contributor.author | Coelho, Teresa | |
dc.contributor.author | Bonilla, Alfonso | |
dc.contributor.author | Pouget, Jean | |
dc.contributor.author | Conceicao, Isabel | |
dc.contributor.author | Berk, John | |
dc.contributor.author | Schmidt, Hartmut | |
dc.contributor.author | Waddington-Cruz, Marcia | |
dc.contributor.author | Campistol, Josep M | |
dc.contributor.author | Bettencourt, Brian R | |
dc.contributor.author | Vaishnaw, Akshay | |
dc.contributor.author | Gollob, Jared | |
dc.contributor.author | Adams, David | |
dc.date.accessioned | 2024-07-04T12:56:26Z | |
dc.date.available | 2024-07-04T12:56:26Z | |
dc.date.issued | 2015-09-04 | |
dc.identifier.citation | Suhr Ole B, Coelho T, Buades-Reine'S J, Pouget J, Conceicao I, Berk J, et al. Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study. Orphanet J Rare Dis. 2015 Sep 04;10:109. | en |
dc.identifier.issn | 1750-1172 | |
dc.identifier.other | http://hdl.handle.net/20.500.13003/10700 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/20141 | |
dc.description.abstract | Background: Transthyretin-mediated amyloidosis is an inherited, progressively debilitating disease caused by mutations in the transthyretin gene. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of patisiran (ALN-TTR02), a small interfering RNA encapsulated within lipid nanoparticles, in patients with transthyretin-mediated familial amyloid polyneuropathy (FAP). Methods: In this phase II study, patients with FAP were administered 2 intravenous infusions of patisiran at one of the following doses: 0.01 (n = 4), 0.05 (n = 3), 0.15 (n = 3), or 0.3 (n = 7) mg/kg every 4 weeks (Q4W), or 0.3 mg/kg (n = 12) every 3 weeks (Q3W). Results: Of 29 patients in the intent-to-treat population, 26 completed the study. Administration of patisiran led to rapid, dose-dependent, and durable knockdown of transthyretin, with the maximum effect seen with patisiran 0.3 mg/kg; levels of mutant and wild-type transthyretin were reduced to a similar extent in Val30Met patients. A mean level of knockdown exceeding 85 % after the second dose, with maximum knockdown of 96 %, was observed for the Q3W dose. The most common treatment-related adverse event (AE) was mild-to-moderate infusion-related reactions in 10.3 % of patients. Four serious AEs (SAEs) were reported in 1 patient administered 0.3 mg/kg Q3W (urinary tract infection, sepsis, nausea, vomiting), and 1 patient administered 0.3 mg/kg Q4W had 1 SAE (extravasation-related cellulitis). Conclusions: Patisiran was generally well tolerated and resulted in significant dose-dependent knockdown of transthyretin protein in patients with FAP. Patisiran 0.3 mg/kg Q3W is currently in phase III development. | en |
dc.description.sponsorship | All authors were responsible for reviewing and interpreting the data. The authors received editorial support from Adelphi Communications Ltd. Biostatistical analyses were conducted by Veristat LLC, Holliston, MA, USA. The authors acknowledge the support of the following co-investigators: Mercedes Uson, Carles Montala, and Cristina Descals (Hospital Son Llatzer, Palma de Mallorca, Spain), and Cecile Cauquil and Marie Theaudin (Univ Paris-Sud, Le Kremlin-Bicetre, Paris, France). The authors also acknowledge contributions from Dorothee Lamann (Universitatsklinikum Munster, Munster, Germany) who provided technical support and Vanessa Benito who was the Study Coordinator at the Hospital Son Llatzer, Palma de Mallorca, Spain. This study was sponsored by Alnylam Pharmaceuticals, Inc. | es_ES |
dc.language.iso | eng | en |
dc.publisher | BioMed Central (BMC) | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Patisiran | en |
dc.subject | RNA interference | en |
dc.subject | Transthyretin-mediated familial amyloidotic polyneuropathy | en |
dc.subject | Polyneuropathy | en |
dc.subject | Hereditary disease | en |
dc.subject | Genetic mutation | en |
dc.subject | Phase II | en |
dc.subject | Clinical trial | en |
dc.subject.mesh | RNA, Small Interfering | * |
dc.subject.mesh | Aged | * |
dc.subject.mesh | Male | * |
dc.subject.mesh | Dose-Response Relationship, Drug | * |
dc.subject.mesh | Female | * |
dc.subject.mesh | Humans | * |
dc.subject.mesh | Middle Aged | * |
dc.subject.mesh | Amyloid Neuropathies, Familial | * |
dc.title | Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study | en |
dc.type | research article | en |
dc.rights.license | Attribution 4.0 International | * |
dc.identifier.pubmedID | 26338094 | es_ES |
dc.format.volume | 10 | es_ES |
dc.format.page | 109 | es_ES |
dc.identifier.doi | 10.1186/s13023-015-0326-6 | |
dc.relation.publisherversion | https://dx.doi.org/10.1186/s13023-015-0326-6 | en |
dc.identifier.journal | Orphanet Journal of Rare Diseases | es_ES |
dc.rights.accessRights | open access | en |
dc.subject.decs | Neuropatías Amiloides Familiares | * |
dc.subject.decs | Relación Dosis-Respuesta a Droga | * |
dc.subject.decs | Humanos | * |
dc.subject.decs | Persona de Mediana Edad | * |
dc.subject.decs | Anciano | * |
dc.subject.decs | Femenino | * |
dc.subject.decs | ARN Interferente Pequeño | * |
dc.subject.decs | Masculino | * |
dc.identifier.scopus | 2-s2.0-84940759062 | |
dc.identifier.wos | 360525400002 | |
dc.identifier.pui | L605848775 | |