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

Randomized, 16-Week, Multi-Phase, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Fulranumab as Adjunctive Therapy in Subjects With Signs and Symptoms of Osteoarthritis of the Hip or Knee

The purpose of this study is to demonstrate the efficacy, safety, and tolerability of fulranumab as adjunctive therapy compared with placebo in participants with chronic moderate to severe pain and functional impairment from knee or hip osteoarthritis that is not adequately controlled by current pain therapy.

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