A single pivotal adaptive trial in infants with proliferating hemangioma: Rationale, design challenges, experience and recommendations

Stephane Heritier, Caroline C. Morgan-Bouniol, Serigne N. Lo, Stephanie Gautier, Jean Jacques Voisard

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

4 Citations (Scopus)

Abstract

This chapter reflects on our experience when designing and analysing an adaptive confirmatory trial (previously referred to as a seamless Phase II/III trial) in infants with hemangioma over the 2009-2013 period. At the end of the first stage (Phase II) an interim analysis was conducted by an independent data monitoring committee allowing three possible adaptations: 1) selection of one or two active treatment regimens for further study in the second stage (Phase III); 2) sample size reestimation; 3) early stopping for futility. The trial design was defended before the FDA and the EMA prior to trial initiation in 2010, and the primary endpoint was analyzed in 2012. Marketing authorization for the pediatric drug Hemangeol (propranolol hydrochloride) was granted to the sponsor, Pierre Fabre Dermatologie, by the FDA (for orphan indication) in March 2014, and by the EMA in April 2014 under a different spelling (Hemangiol). Hemangeol is the first and only approved treatment for “proliferating infantile hemangioma requiring systemic therapy”. This single pivotal trial is one of the first adaptive confirmatory trials to be conducted successfully in the regulatory setting.

Original languageEnglish
Title of host publicationModern Adaptive Randomized Clinical Trials
Subtitle of host publicationStatistical and Practical Aspects
EditorsOleksandr Sverdlov
Place of PublicationBoca Raton FL USA
PublisherCRC Press
Pages453-482
Number of pages30
ISBN (Electronic)9781482239898
ISBN (Print)9781482239881
DOIs
Publication statusPublished - Jun 2015

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