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

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the efficacy, safety, and tolerability of fulranumab as adjunctive therapy compared with placebo in participants with signs and symptoms of osteoarthritis of the hip or knee that are not adequately controlled by current pain therapy.

Detailed Description
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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.

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

Conditions
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Osteoarthritis, Pain

Intervention / Treatment
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* Drug: Placebo
* Drug: Fulranumab 1 mg
* Drug: Fulranumab 3 mg
* Drug: Celecoxib 100 mg
* Drug: Celecoxib 100 mg Matching Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive 4 subcutaneous (SC) injections (one injection every 4 weeks) of placebo during the double-blind treatment phase. In addition, participants may take adjunctive therapy with celecoxib 100 mg orally (by mouth) twice daily for up to 16 weeks. | Drug: Placebo<br>* Placebo will be administered once every 4 weeks with or without adjunctive therapy for 16 weeks by subcutaneous (SC) injection (injection under the skin) into the thigh or abdomen.<br>Drug: Celecoxib 100 mg<br>* Double-blind capsules taken twice daily for up to 16 weeks.<br>|
| Experimental: Fulranumab 1 mg<br>Participants will receive 4 subcutaneous (SC) injections (one injection every 4 weeks) of fulranumab 1 mg during the double-blind treatment phase. In addition, participants may take adjunctive therapy with celecoxib placebo orally twice daily for up to 16 weeks. | Drug: Fulranumab 1 mg<br>* Fulranumab will be administered once every 4 weeks with or without adjunctive therapy for up to 16 weeks by SC injection into the thigh or abdomen.<br>Drug: Celecoxib 100 mg Matching Placebo<br>* Double-blind capsules taken twice daily for up to 16 weeks.<br>|
| Experimental: Fulranumab 3 mg<br>Participants will receive 4 subcutaneous (SC) injections (one injection every 4 weeks) of fulranumab 3 mg during the double-blind treatment phase. In addition, participants may take adjunctive therapy with celecoxib placebo orally twice daily for up to 16 weeks. | Drug: Fulranumab 3 mg<br>* Fulranumab will be administered once every 4 weeks with or without adjunctive therapy for up to 16 weeks by SC injection into the thigh or abdomen.<br>Drug: Celecoxib 100 mg Matching Placebo<br>* Double-blind capsules taken twice daily for up to 16 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of participants with Adverse Events as a measure of safety and tolerability |  | Up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to the end of Week 16 in Western Ontario and McMaster University Arthritis Index (WOMAC) pain subscale score | The WOMAC 3.1 is a multi-dimensional, osteoarthritis (OA) specific self-administered questionnaire using 24 questions with a 48-hour recall that are grouped into 3 subscales (pain, stiffness, and physical function) associated with hip or knee OA. Pain, stiffness, and physical function is rated on a scale of 0-10 (0 = less severe up to 10 = more severe). | Baseline, Week 16 | 
| Change from baseline to the end of Week 16 in Western Ontario and McMaster University Arthritis Index (WOMAC) physical function subscale score | See WOMAC 3.1 described above. | Baseline, Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Pain, Fulranumab, JNJ-42160443, Adjunctive therapy, Celecoxib, Hip, Knee, Joint replacement surgery