Safety assessments
Safety assessments at screening included physical examination, full dermatologic examination, ophthalmic examination, assessment of vital signs (blood pressure, temperature, pulse and respiratory rate) and electrocardiogram and echocardiogram. During treatment, a brief dermatologic examination was performed monthly, and an ophthalmic examination was performed only after the first month unless clinically indicated thereafter. Monthly assessment of vital signs and electrocardiogram were also required during treatment, and an echocardiogram was performed after the first month and every 3 months thereafter. Besides the parameters described in the protocol, additional safety tests were to be performed by the investigators during the course of the study based on newly available data to ensure appropriate safety monitoring. Appropriate local regulatory and ethical approvals applied before any additional testing was performed.AE monitoring was done continuously from the time the first dose of study treatment was administered until 30 days after discontinuation of study treatment. AEs were graded according to CTCAE version 4.0 (ref. 