Study of Efficacy, Safety of Fulranumab Adjunctive Use in OA of Hip or Knee, PAI3001

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. All participants will be allowed standard of care for OA pain during the double-blind
treatment phase and must be taking an opioid at study entry and during the double-blind
treatment phase. 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

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

- 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