Study of Safety, Efficacy of Fulranumab Adjunctive Use in OA of Hip or Knee, PAI3007

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 adjunctive therapy (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. In addition, participants may elect to receive adjunctive therapy (ie,
double-blind supplemental oral analgesic medication or matching placebo) throughout the
double-blind treatment period. 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

- Unsatisfactory response (inadequate efficacy or poor tolerability) on local standard
of care that includes 3 medications from at least 2 of the following classes of
analgesic medications (acetaminophen/paracetamol, NSAIDs, or opioid). For
participants in the USA and Canada only: 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