Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy

David Adams, Ole B. Suhr, Peter J. Dyck, William J. Litchy, Raina G. Leahy, Jihong Chen, Jared Gollob, Teresa Coelho

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number181
JournalBMC neurology
Volume17
Issue number1
DOIs
StatePublished - Sep 11 2017

Keywords

  • APOLLO
  • HATTR amyloidosis
  • MNIS+7
  • Methods
  • Patisiran
  • Polyneuropathy
  • RNA interference

ASJC Scopus subject areas

  • Clinical Neurology

Fingerprint Dive into the research topics of 'Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy'. Together they form a unique fingerprint.

Cite this