The national blueprint for future factor VIII inhibitor clinical trials: NHLBI State of the Science (SOS) Workshop on factor VIII inhibitors.
clinical trials
haemophilia
inherited bleeding disorders
inhibitor formation
Journal
Haemophilia : the official journal of the World Federation of Hemophilia
ISSN: 1365-2516
Titre abrégé: Haemophilia
Pays: England
ID NLM: 9442916
Informations de publication
Date de publication:
Jul 2019
Jul 2019
Historique:
received:
26
11
2018
revised:
29
12
2018
accepted:
31
01
2019
entrez:
23
7
2019
pubmed:
23
7
2019
medline:
19
12
2019
Statut:
ppublish
Résumé
Inhibitor formation is a major complication of haemophilia for which clinical trials are planned. Despite emerging novel haemostatic agents, challenges of rare disease trials are limited subjects and lack of an organized research organization with strategic resources and partnerships. The charge to Working Group 1 was to establish scientific priorities and innovative implementation strategies to conduct inhibitor prevention and eradication trials. To determine feasibility of trial design and strategic resources and partnerships to be leveraged, two clinical trial concepts were considered. For the Inhibitor Prevention Trial, we considered adaptive design with early stopping rules, dynamic randomization and Master Protocol models to reduce sample size; and registries to provide concurrent controls and natural history data. For the Inhibitor Eradication Trial using gene therapy, an adaptive design was considered in a small number of subjects, and, if safe and meeting regulatory requirements, enrolment would be expanded. A Haemophilia Clinical Trials Group (HCTG) infrastructure was envisioned, with uniform procedures and standardized outcomes, data collection and assays, within which trial concepts would be developed, vetted and prioritized by a Steering Committee, and submitted to NIH and other research sponsors for review and funding. Mechanistic studies would be embedded within the trials, early stage investigators trained and mentored, and the research infrastructure established within the haemophilia centre (HTC) network and supported by partnerships with foundations, community, federal partners and industry. The success of inhibitor trials will depend on innovative trial design and an organized HCTG research infrastructure, leveraged through community partnerships.
Identifiants
pubmed: 31329364
doi: 10.1111/hae.13717
pmc: PMC9883697
mid: NIHMS1864187
doi:
Substances chimiques
Factor VIII
9001-27-8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
581-589Subventions
Organisme : NHLBI NIH HHS
ID : K08 HL146991
Pays : United States
Informations de copyright
Publication 2019. This article is a U.S. Government work and is in the public domain in the USA.
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