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Efficacy and safety...
Efficacy and safety of patisiran for familial amyloidotic polyneuropathy : a phase II multi-dose study
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- Suhr, Ole B. (author)
- Umeå universitet,Medicin
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Coelho, Teresa (author)
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Buades, Juan (author)
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Pouget, Jean (author)
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Conceicao, Isabel (author)
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Berk, John (author)
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Schmidt, Hartmut (author)
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Waddington-Cruz, Marcia (author)
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Campistol, Josep M. (author)
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Bettencourt, Brian R. (author)
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Vaishnaw, Akshay (author)
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Gollob, Jared (author)
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Adams, David (author)
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(creator_code:org_t)
- 2015-09-04
- 2015
- English.
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In: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 10
- Related links:
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https://ojrd.biomedc...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- Patisiran
- RNA interference
- Transthyretin-mediated familial amyloidotic polyneuropathy
- Polyneuropathy
- Hereditary disease
- Genetic mutation
- Phase II
- Clinical trial
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Suhr, Ole B.
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Coelho, Teresa
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Buades, Juan
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Pouget, Jean
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Conceicao, Isabe ...
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Berk, John
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show more...
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Schmidt, Hartmut
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Waddington-Cruz, ...
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Campistol, Josep ...
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Bettencourt, Bri ...
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Vaishnaw, Akshay
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Gollob, Jared
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Adams, David
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Orphanet Journal ...
- By the university
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Umeå University