Repository logo
 
Publication

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

2015Journal article Open access
Simple item page
dc.contributor.authorSuhr, O.
dc.contributor.authorCoelho, T.
dc.contributor.authorBuades, J.
dc.contributor.authorPouget, J.
dc.contributor.authorConceicao, I.
dc.contributor.authorBerk, J.
dc.contributor.authorSchmidt, H.
dc.contributor.authorWaddington-Cruz, M.
dc.contributor.authorCampistol, J.
dc.contributor.authorBettencourt, B.
dc.contributor.authorVaishnaw, A.
dc.contributor.authorGollob, J.
dc.contributor.authorAdams, D.
dc.date.accessioned2016-08-01T09:54:28Z
dc.date.available2016-08-01T09:54:28Z
dc.date.issued2015
dc.description.abstractBACKGROUND: 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).pt_PT
dc.description.abstractMETHODS: 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).pt_PT
dc.description.abstractRESULTS: 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).pt_PT
dc.description.abstractCONCLUSIONS: 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.pt_PT
dc.identifier.citationOrphanet J Rare Dis. 2015 Sep 4;10:109.pt_PT
dc.identifier.doi10.1186/s13023-015-0326-6pt_PT
dc.identifier.issn1750-1172
dc.identifier.urihttp://hdl.handle.net/10400.16/1984
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBioMed Centralpt_PT
dc.relation.publisherversionhttp://download.springer.com/static/pdf/256/art%253A10.1186%252Fs13023-015-0326-6.pdf?originUrl=http%3A%2F%2Fojrd.biomedcentral.com%2Farticle%2F10.1186%2Fs13023-015-0326-6&token2=exp=1470044958~acl=%2Fstatic%2Fpdf%2F256%2Fart%25253A10.1186%25252Fs13023-015-0326-6.pdf*~hmac=55a82b8f504725d86096efb68ea3a8edb789fb53c3de39f5824cbee78830f961pt_PT
dc.subjectPatisiranpt_PT
dc.subjectRNA interferencpt_PT
dc.subjectTransthyretin-mediated familial amyloidotic polyneuropathypt_PT
dc.subjectPolyneuropathypt_PT
dc.subjectHereditary diseasept_PT
dc.subjectGenetic mutationpt_PT
dc.subjectPhase IIpt_PT
dc.subjectClinical trialpt_PT
dc.titleEfficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose studypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceEnglandpt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage109pt_PT
oaire.citation.titleOrphanet Journal of Rare Diseasespt_PT
oaire.citation.volume10pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Efficacy and safety of patisiran.pdf
Size:
583.22 KB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.35 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

SNF - Artigos publicados em revistas indexadas na Pubmed/Medline