Study of Efficacy, Safety of Fulranumab Monotherapy for OA of Hip or Knee, PAI3003

This is a randomized (the study drug is assigned by chance), double-blind (neither physician
nor participant knows the name of the assigned drug), placebo-controlled (an inactive
substance is given to one group of participants while active drug is given to another group
of participants to see if there is a difference in response), parallel-group (study drugs
given to participants in all treatment groups during the same time period) to evaluate the
efficacy (capacity of the investigational drug to produce an effect), safety, and
tolerability of fulranumab administered as monotherapy (alone; not in combination with other
drug therapy) to participants with chronic moderate to severe pain and functional impairment
from knee or hip osteoarthritis (OA) that is not adequately controlled by current pain
therapy. The duration of participation in the study for an individual participant will be up
to 67 weeks (includes a screening period of 3 weeks, a double-blind treatment period of 16
weeks, and a post-treatment follow-up period of up to 48 weeks).). All participants will be
randomly assigned in a 1:1:1 ratio to 1 of 3 treatments (placebo, fulranumab 1mg, fulranumab
3mg) and given a single injection subcutaneously (under the skin) once every 4 weeks for up
to 16 weeks. Blood samples will be collected from each participant at time points during the
study. Safety evaluations will include assessment of adverse events, physical examinations,
laboratory tests and vital signs which will be monitored throughout the study.

Inclusion Criteria:

- Clinical diagnosis of osteoarthritis (OA) of hip or knee based on criteria defined by
the American College of Rheumatology and radiographic evidence of OA
(Kellgren-Lawrence class ≥2) of the study joint

- Scheduled joint replacement or planning to undergo a joint replacement surgery for
the study joint

- Must have an unsatisfactory response (inadequate efficacy or poor tolerability) that
includes all 3 classes of analgesic medications (acetaminophen/paracetamol, NSAID,
and an opioid); For participants in the USA and Canada: Must have an unsatisfactory
response (inadequate efficacy or poor tolerability) that includes all 3 classes of
analgesic medications (acetaminophen/paracetamol, NSAIDs, and opioids other than
codeine or codeine combination products)

- Moderate to severe pain and functional impairment based on the NRS, WOMAC pain and
physical function subscales, and PGA

- During treatment and within 24 weeks after the last injection of study drug: if
female of childbearing potential, is not pregnant, breast-feeding, or planning to
become pregnant, or if male, will not father a child

Exclusion Criteria:

- Increased risk of osteonecrosis (ON) or rapidly progressive osteoarthritis (RPOA)

- Unstable or progressive neurologic disorders