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

Table 1 Key inclusion and exclusion criteria for the APOLLO study

Inclusion criteria	Exclusion criteria
• Diagnosis of hATTR amyloidosis with documented mutation • Anticipated survival ≥2 years • Aged 18–85 years (inclusive) • NIS of 5–130 • PND score ≤IIIb • NCS sum of the sural SNAP, tibial CMAP, ulnar SNAP, ulnar CMAP, and peroneal CMAP of ≥2 points • Karnofsky performance status ≥60% • Absolute neutrophil count ≥1500 cells/mm³ • Platelet count ≥50,000 cells/mm³ • Adequate biochemical liver function^a • Serum creatinine ≤2 × ULN	• Previous liver transplantation, or liver transplantation planned during study period • Sensorimotor or autonomic neuropathy not related to hATTR amyloidosis • Primary or leptomeningeal amyloidosis • Type 1 diabetes • Type 2 diabetes for ≥5 years • Active hepatitis B or C, or HIV infection • NYHA heart failure classification >2 • Acute coronary syndrome within past 3 months • Uncontrolled cardiac arrhythmia or unstable angina • Severe reaction to a liposomal product or hypersensitivity to oligonucleotides • Unable to take premedications • Received an investigational agent within 30 days/5 half-lives (whichever is longer) of study drug administration • Currently taking tafamidis, diflunisal, doxycycline, or tauroursodeoxycholic acid

CMAP compound muscle action potential; hATTR amyloidosis hereditary transthyretin-mediated amyloidosis; NCS nerve conduction study; NIS Neuropathy Impairment Score; NYHA New York Heart Association; PND polyneuropathy disability; SNAP sensory nerve action potential; ULN upper limit of normal
^aAspartate transaminase and alanine transaminase levels ≤2.5 × ULN; total bilirubin levels within normal limits; international normalized ratio ≤2.0

ISSN: 1471-2377