A Randomized Phase IIa Efficacy and Safety Study of Radium-223 Dichloride With Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (CRPC)

The primary objective in this study is to evaluate bone scan response at Week 24 based on the
quantified technetium-99 bone scan lesion area (BSLA). The safety of radium-223 dichloride in
combination with abiraterone acetate or enzalutamide will be investigated. The study will
evaluate radiological progression free survival, overall survival, and skeletal events. This
study will also explore the clinical utility of different imaging modalities (whole body
quantified technetium-99 bone scan, DW-MRI [diffusion-weighted magnetic resonance imaging]
and NaF [sodium fluoride] PET-CT [positron emission tomography-computed tomography] scan) and
will have a separate central radiological review for applicable secondary and exploratory
imaging endpoints. All subjects will be randomized as assigned randomly by the IXRS
(interactive voice / web response system) system in a 1:1:1 ratio into one of the treatment
arms: radium-223 dichloride alone, 50 kBq/kg (55 kBq/kg after implementation of NIST
[National Institute of Standards and Technology] update) every 4 weeks for up to 6 doses;
radium-223 dichloride, 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4
weeks up to 6 doses together with abiraterone acetate 1,000 mg daily and prednisone 5 mg bid
(twice daily); radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST
update) every 4 weeks up to 6 doses together with enzalutamide 160 mg daily. The study will
consist of screening, treatment and follow-up periods. Study will continue until disease
progression as determined by investigator, or when patient meets criteria for withdrawal from
study. Subjects in treatment arms with abiraterone/prednisone or enzalutamide will have the
option to continue taking oral study therapy until the end of the study (2 years from the
last dose of radium-223 dichloride) if the investigator deems the subject may benefit and
there is no clinical or radiological progression. Subjects who discontinue all study
treatment prior to 2 years from last radium-223 dichloride treatment will enter active
follow-up. During the active follow-up period, the subject will have a safety visit at the
clinic every 12 weeks from the EOT (end of treatment) for up to 2 years from the last dose of
radium-223 dichloride. Beyond 2 years from last radium-223 dichloride treatment,subjects will
enter long-term follow-up and will be followed via phone contact at intervals to assess for
safety (hematological toxicity and new primary malignancies) and overall survival. A separate
long-term safety follow-up study protocol is planned. Once implemented, the study subjects
surviving after the end of the active follow-up will be transitioned to this separate
long-term safety follow-up protocol.