BACKGROUND: Patisiran is an investigational RNA interference (RNAi) therapeutic 
in development for the treatment of hereditary ATTR (hATTR) amyloidosis, a 
progressive disease associated with significant disability, morbidity, and 
mortality.
METHODS: Here we describe the rationale and design of the Phase 3 APOLLO study, 
a randomized, double-blind, placebo-controlled, global study to evaluate the 
efficacy and safety of patisiran in patients with hATTR amyloidosis with 
polyneuropathy. Eligible patients are 18-85 years old with hATTR amyloidosis, 
investigator-estimated survival of ≥2 years, Neuropathy Impairment Score (NIS) 
of 5-130, and polyneuropathy disability score ≤IIIb. Patients are randomized 2:1 
to receive either intravenous patisiran 0.3 mg/kg or placebo once every 3 weeks. 
The primary objective is to determine the efficacy of patisiran at 18 months 
based on the difference in the change in modified NIS+7 (a composite measure of 
motor strength, sensation, reflexes, nerve conduction, and autonomic function) 
between the patisiran and placebo groups. Secondary objectives are to evaluate 
the effect of patisiran on Norfolk-Diabetic Neuropathy quality of life 
questionnaire score, nutritional status (as evaluated by modified body mass 
index), motor function (as measured by NIS-weakness and timed 10-m walk test), 
and autonomic symptoms (as measured by the Composite Autonomic Symptom Score-31 
questionnaire). Exploratory objectives include assessment of cardiac function 
and pathologic evaluation to assess nerve fiber innervation and amyloid burden. 
Safety of patisiran will be assessed throughout the study.
DISCUSSION: APOLLO represents the largest randomized, Phase 3 study to date in 
patients with hATTR amyloidosis, with endpoints that capture the multisystemic 
nature of this disease.
TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov ( NCT01960348 
); October 9, 2013.