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

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to demonstrate the efficacy, safety, and tolerability of fulranumab as Monotherapy 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
-----------------
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.

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

Conditions
-----------------
Osteoarthritis, Pain

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: Fulranumab 1 mg
* Drug: Fulranumab 3 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
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

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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. | Drug: Placebo<br>* Placebo will be administered once every 4 weeks for 16 weeks by subcutaneous (SC) injection (injection under the skin) into the thigh or abdomen.<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. | Drug: Fulranumab 1 mg<br>* Fulranumab will be administered once every 4 weeks for up to 16 weeks by SC injection into the thigh or abdomen.<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. | Drug: Fulranumab 3 mg<br>* Fulranumab will be administered once every 4 weeks for up to 16 weeks by SC injection into the thigh or abdomen.<br>|

What is the study measuring?
-----------------
Primary 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 | 
| Change from baseline to the end of Week 16 in Patient Global Assessment (PGA) score | The PGA is part of a comprehensive assessment of the impact of treatment for osteoarthritis that also includes pain and physical function. The PGA included in the present study indicates the perception of osteoarthritis in the study joint at the current time. Ratings are provided on an 11-point numerical rating scale from 0 (Very Good) to 10 (Very Bad). | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to the end of Week 16 in Patient Global Assessment (PGA) score | See PGA described above. | Baseline, Week 16 | 
| Change from baseline to the end of Week 16 in WOMAC Stiffness subscale score | See WOMAC 3.1 described above. | Baseline, Week 16 | 
| Change from baseline to the end of Week 16 in daily numerical rating scale (NRS) score | The numerical rating scale (NRS) uses an 11-point scale to assess OA pain ranging from 0 to 10 with high scores representing greater symptom severity (0=no pain and 10=pain as bad as you can imagine). | Baseline, Week 16 | 
| Change from baseline to the end of Week 16 in Medical Outcomes Study (MOS) Sleep subscale scores | The MOS Sleep Scale (acute version) contains 12 items that address aspects of sleep. Six subscale scores may be calculated including: daytime somnolence, sleep disturbances, snoring, shortness of breath or headache upon awaking, adequacy of sleep and amount of sleep plus a summary index of sleep disturbances. A higher score indicates worse sleep in most domains, but the amount of sleep and adequacy of sleep are scored in the opposite direction.The primary subscale of interest in this study is daytime somnolence. | Baseline, Week 16 | 
| Change from baseline to the end of Week 16 in Short-Form--36 (SF-36) subscale scores | The SF-36 is a self-administered, generic, 36-item questionnaire designed to cover 8 domains of functional health status and well-being, physical functioning, role limitations due to physical health problems, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health.Scoring yields 8 subscales based on the 8 domains covered in the questionnaire. These scales are scored from 0 to 100 with higher scores indicating better health. | Baseline, Week 16 | 
| Change from baseline to the end of Week 16 in EuroQol, 5 dimensions, 5 levels (EQ-5D-5L) scale score | The EQ-5D is a self-administered, standardized measure of health status designed to provide a generic measure of health for clinical and economic appraisal that includes the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D 5 level (5L) version will be used in this study. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and unable or extreme problems. A unique health state is defined by combining 1 level from each of the 5 dimensions. | Baseline, Week 16 | 
| Change from baseline to the end of Week 16 in the percentage of participants who are responders based on WOMAC pain and physical function subscale scores and PGA scale scores | Responders are defined as participants with percent improvement equal to and above the threshold values for WOMAC pain and physical function subscale scores and PGA scale scores, reported separately. | Baseline, Week 16 | 
| Change from baseline to the end of Week 16 in the percentage of participants who are responders based on OMERACT-OARSI, MCII, and PASS scale scores | Responders are defined as participants with percent improvement equal to and above the threshold values for Outcome Measures in Rheumatology initiative/Osteoarthritis Research Society International (OMERACT-OARSI), Minimal Clinically Important Improvement (MCII), and the Patient Acceptable Symptom State (PASS) scale scores. | Baseline, Week 16 | 
| Change from baseline to the end of Week 16 in the percentage of participants who use rescue medication and other osteoarthritis (OA) analgesia | Use of rescue medication (acetaminophen/paracetamol) and other OA pain medication will be recorded weekly during the study. | Baseline, Week 16 | 

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