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.
|Title of host publication||Modern Adaptive Randomized Clinical Trials|
|Subtitle of host publication||Statistical and Practical Aspects|
|Place of Publication||Boca Raton FL USA|
|Number of pages||30|
|Publication status||Published - Jun 2015|