Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study

Detalhes bibliográficos
Autor(a) principal: Suhr, O.
Data de Publicação: 2015
Outros Autores: Coelho, T., Buades, J., Pouget, J., Conceicao, I., Berk, J., Schmidt, H., Waddington-Cruz, M., Campistol, J., Bettencourt, B., Vaishnaw, A., Gollob, J., Adams, D.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.16/1984
Resumo: 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).
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spelling Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose studyPatisiranRNA interferencTransthyretin-mediated familial amyloidotic polyneuropathyPolyneuropathyHereditary diseaseGenetic mutationPhase IIClinical trialBACKGROUND: 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.BioMed CentralRepositório Científico do Centro Hospitalar Universitário de Santo AntónioSuhr, O.Coelho, T.Buades, J.Pouget, J.Conceicao, I.Berk, J.Schmidt, H.Waddington-Cruz, M.Campistol, J.Bettencourt, B.Vaishnaw, A.Gollob, J.Adams, D.2016-08-01T09:54:28Z20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.16/1984engOrphanet J Rare Dis. 2015 Sep 4;10:109.1750-117210.1186/s13023-015-0326-6info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-20T10:58:33Zoai:repositorio.chporto.pt:10400.16/1984Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:38:17.353050Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study
title Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study
spellingShingle Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study
Suhr, O.
Patisiran
RNA interferenc
Transthyretin-mediated familial amyloidotic polyneuropathy
Polyneuropathy
Hereditary disease
Genetic mutation
Phase II
Clinical trial
title_short Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study
title_full Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study
title_fullStr Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study
title_full_unstemmed Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study
title_sort Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study
author Suhr, O.
author_facet Suhr, O.
Coelho, T.
Buades, J.
Pouget, J.
Conceicao, I.
Berk, J.
Schmidt, H.
Waddington-Cruz, M.
Campistol, J.
Bettencourt, B.
Vaishnaw, A.
Gollob, J.
Adams, D.
author_role author
author2 Coelho, T.
Buades, J.
Pouget, J.
Conceicao, I.
Berk, J.
Schmidt, H.
Waddington-Cruz, M.
Campistol, J.
Bettencourt, B.
Vaishnaw, A.
Gollob, J.
Adams, D.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Centro Hospitalar Universitário de Santo António
dc.contributor.author.fl_str_mv Suhr, O.
Coelho, T.
Buades, J.
Pouget, J.
Conceicao, I.
Berk, J.
Schmidt, H.
Waddington-Cruz, M.
Campistol, J.
Bettencourt, B.
Vaishnaw, A.
Gollob, J.
Adams, D.
dc.subject.por.fl_str_mv Patisiran
RNA interferenc
Transthyretin-mediated familial amyloidotic polyneuropathy
Polyneuropathy
Hereditary disease
Genetic mutation
Phase II
Clinical trial
topic Patisiran
RNA interferenc
Transthyretin-mediated familial amyloidotic polyneuropathy
Polyneuropathy
Hereditary disease
Genetic mutation
Phase II
Clinical trial
description 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).
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-01-01T00:00:00Z
2016-08-01T09:54:28Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.16/1984
url http://hdl.handle.net/10400.16/1984
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Orphanet J Rare Dis. 2015 Sep 4;10:109.
1750-1172
10.1186/s13023-015-0326-6
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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