A Study to Determine the Safety and the Efficacy of Fasinumab Compared to Placebo and Naproxen for Treatment of Adults With Pain From Osteoarthritis of the Knee or Hip

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the efficacy of fasinumab compared with placebo, when administered for up to 16 weeks in patients with pain due to osteoarthritis (OA) of the knee or hip. The secondary objectives of the study are: To evaluate the efficacy of fasinumab compared with naproxen, when administered for up to 16 weeks in patients with pain due to OA of the knee or hip To evaluate the efficacy of fasinumab compared with placebo, when administered for up to 44 weeks in patients with pain due to OA of the knee or hip To assess the safety and tolerability of fasinumab compared with naproxen, when administered for up to 16 weeks in patients with pain due to OA of the knee or hip To assess the safety and tolerability of fasinumab compared with naproxen, when administered for up to 52 weeks in patients with pain due to OA of the knee or hip To assess the safety and tolerability of fasinumab compared with naproxen, when administered for up to 104 weeks in patients with pain due to OA of the knee or hip To evaluate the pharmacokinetic (PK) profile of fasinumab administered to patients with pain due to OA of the knee or hip for up to 52 weeks To evaluate the PK profile of fasimumab administered to patients with pain due to OA of the knee or hip for up to 104 weeks To evaluate the immunogenicity of fasinumab administered to patients with pain due to OA of the knee or hip for up to 52 weeks To evaluate the immunogenicity of fasinumab administered to patients with pain due to OA of the knee or hip for up to 104 weeks To evaluate the efficacy of fasinumab compared with naproxen, when administered for up to 44 weeks in patients with pain due to OA of the knee or hip

Official Title
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A Phase 3 Randomized, Double-blind, Multi-dose, Placebo and Naproxen-Controlled Study to Evaluate the Efficacy and Safety of Fasinumab in Patients With Pain Due to Osteoarthritis of the Knee or Hip

Conditions
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Osteoarthritis, Knee, Osteoarthritis, Hip

Intervention / Treatment
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* Drug: Fasinumab
* Drug: Naproxen
* Drug: Fasinumab-matching placebo
* Drug: Naproxen-matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria include, but are not limited to, the following: Year 1: Male and female patients, at least 18 years of age, at screening A clinical diagnosis of OA of the knee or hip based on the American College of Rheumatology criteria with radiologic evidence of OA (K-L score ≥2 for the index joint) at the screening visit Moderate to severe pain in the index joint defined at both the screening and randomization visits Willing to discontinue current pain medications and to adhere to study requirements for rescue treatments (acetaminophen/paracetamol) to be taken as needed with a maximum daily dose of 2500 mg (countries where 500 mg strength tablets/capsules are available) or 2600 mg (countries where 325 mg strength tablets/capsules are available) A history of at least 12 weeks of analgesics use for pain due to OA of the knee or hip, as defined by: Inadequate pain relief from acetaminophen/paracetamol AND Intolerance to or inadequate pain relief from opioid or tramadol therapy, unwillingness to take opioid or tramadol therapy for a medically acceptable reason, or lack of access to an opioid or to tramadol Currently using a stable dose of NSAID. Willing to discontinue glucosamine sulfate and chondroitin sulfate treatments during the initial 16 weeks of treatment Stable treatment with glucosamine sulfate and chondroitin sulfate treatments must be stopped during the pre-randomization period Consent to allow all radiographs and medical/surgical/hospitalization records of care received elsewhere prior to and during the study period to be shared with the investigator Willing to maintain current activity and exercise levels throughout the study Willing and able to comply with clinic visits and study-related procedures and willing to provide follow-up information related to any JR surgery that occurs within the period of time covered by their intended participation in the study Able to understand and complete study-related questionnaires Year 2: Note: Any Year 1 patient attending their week 52 visit on or after 26 March 2020 will no longer have the option to enroll into Year 2. Completed the treatment period of Year 1 Did not permanently discontinue study drug during Year 1 Received no less than 10 of the 13 planned doses of SC study drug during the treatment period of Year 1 Provide informed consent for Year 2 Willing to continue to maintain current activity and exercise levels throughout Year 2 Exclusion Criteria include, but are not limited to, the following: Non-compliance with the Numeric Rating Scale (NRS) recording during the pre-randomization period History or presence at the screening visit of non-OA inflammatory joint disease, Paget's disease of the spine, pelvis or femur, neuropathic disorders, multiple sclerosis, fibromyalgia, tumors or infections of the spinal cord, or renal osteodystrophy History or presence on imaging of arthropathy, neuropathic joint arthropathy, hip or knee dislocation, extensive subchondral cysts, significant bone collapse or bone loss, or pathologic fractures Trauma to the index joint within 3 months prior to the screening visit Signs or symptoms of carpal tunnel syndrome within 6 months of screening Patient is not a candidate for MRI Is scheduled for a JR surgery to be performed during the study period or who would be unwilling or unable to undergo JR surgery if needed History or presence at the screening visit of autonomic or diabetic neuropathy, or other peripheral neuropathy, including reflex sympathetic dystrophy History or diagnosis of chronic autonomic failure syndrome including pure autonomic failure, multiple system atrophy History of naproxen intolerance, or existence of a medical condition that is high risk for naproxen-associated complications Resting heart rate of <50 beats per minute (bpm) or >100 bpm at the screening or randomization visits History or presence of 2nd or 3rd degree heart block, 1st degree heart block with abnormal Complex of Q, R, and S waves on an electrocardiogram (QRS) complex, or bifascicular block by ECG assessment at the screening visit History or presence of orthostatic hypotension at the screening, prerandomization, or randomization visits History of poorly controlled hypertension Use of systemic corticosteroid within 30 days prior to the screening visit. Intra-articular corticosteroids in the index joint within 12 weeks prior to the screening visit, or to any other joint within 30 days prior to the screening visit Exposure to an anti-Nerve growth factor (NGF) antibody prior to the screening visit or known sensitivity or intolerance to anti-NGF antibodies

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fasinumab dosing regimen 1<br>Fasinumab Subcutaneous (SC) dosing regimen 1 and naproxen-matching placebo oral | Drug: Fasinumab<br>* Solution for injection in pre-filled syringe<br>* Other names: REGN475;Drug: Naproxen-matching placebo<br>* Capsule<br>|
| Experimental: Fasinumab dosing regimen 2<br>Fasinumab SC dosing regimen 2 and naproxen-matching placebo oral | Drug: Fasinumab<br>* Solution for injection in pre-filled syringe<br>* Other names: REGN475;Drug: Naproxen-matching placebo<br>* Capsule<br>|
| Experimental: Fasinumab-matching placebo and naproxen<br> | Drug: Naproxen<br>* Pharmaceutical form: Capsule<br>Drug: Fasinumab-matching placebo<br>* Solution for injection in pre-filled syringe<br>|
| Experimental: Fasinumab-matching placebo and naproxen-matching placebo<br> | Drug: Fasinumab-matching placebo<br>* Solution for injection in pre-filled syringe<br>Drug: Naproxen-matching placebo<br>* Capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the WOMAC Pain Subscale Scores From Baseline to Week 16 in Participants Treated With Fasinumab 1mg SC Q4W Compared With That of Participants Treated With Placebo | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 16 | 
| Change in the WOMAC Physical Function Subscale Scores From Baseline to Week 16 in Participants Treated With Fasinumab 1mg Q4W Compared With That of Participants Treated With Placebo | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 16 | 
| Change in the WOMAC Pain Subscale Scores From Baseline to Week 16 in Participants Treated With Fasinumab 1mg SC Q8W Compared With That of Participants Treated With Placebo | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 16 | 
| Change in the WOMAC Physical Function Subscale Scores From Baseline to Week 16 in Participants Treated With Fasinumab 1mg Q8W Compared With That of Participants Treated With Placebo | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Patient Global Assessment (PGA) Scores From Baseline to Week 16 in Participants Treated With Fasinumab 1mg Q4W Compared With That of Participants Treated With Placebo | The Patient Global Assessment of OA (PGA) is a patient-rated assessment of current disease state on a 5-point Likert scale (1 = very good; 2 = good; 3 = fair; 4 = poor; and 5 = very poor). | Baseline to Week 16 | 
| Change in the PGA Scores From Baseline to Week 16 in Participants Treated With Fasinumab 1mg Q4W Compared With That of Participants Treated With Naproxen | The Patient Global Assessment of OA (PGA) is a patient-rated assessment of current disease state on a 5-point Likert scale (1 = very good; 2 = good; 3 = fair; 4 = poor; and 5 = very poor). | Baseline to Week 16 | 
| Change In The PGA Scores From Baseline To Week 44 In Participants Treated With Fasinumab 1mg Q4W Compared With That Of Participants Treated With Placebo | The Patient Global Assessment of OA (PGA) is a patient-rated assessment of current disease state on a 5-point Likert scale (1 = very good; 2 = good; 3 = fair; 4 = poor; and 5 = very poor). | Baseline to Week 44 | 
| Percentage Of Participants Treated With Fasinumab 1mg Q4W, Compared With That of Participants Treated With Placebo, Who Had A Response At Week 16, With Response Defined As An Improvement By ≥30% In The WOMAC Pain Subscale Scores | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 16 | 
| Percentage of Participants Treated With Fasinumab 1mg Q4W, Compared With That of Participants Treated With Naproxen, Who Had A Response At Week 16, With Response Defined As An Improvement By ≥30% In The WOMAC Pain Subscale Scores | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Week 16 | 
| Change in WOMAC Pain Subscale Scores From Baseline to Week 16 In Participants Treated With Fasinumab 1mg Q4W, Compared With That of Participants Treated With Naproxen | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 16 | 
| Change in WOMAC Pain Subscale Scores From Baseline to Week 44 in Participants Treated With Fasinumab 1mg Q4W, Compared With That of Participants Treated With Placebo | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 44 | 
| Change in WOMAC Pain Subscale Scores From Baseline to Week 44 in Participants Treated With Fasinumab 1 mg Q4W, Compared With That of Participants Treated With Naproxen | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 44 | 
| Change in WOMAC Physical Function Subscale Scores From Baseline to the Average Score Across Weeks 4, 8, 12 and 16, in Participants Treated With Fasinumab 1 mg Q4W Compared With That of Participants Treated With Placebo | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to average score across weeks 4, 8, 12 and 16 | 
| Change in WOMAC Physical Function Subscale Scores From Baseline to the Average Score Across Weeks 36, 40 and 44 in Participants Treated With Fasinumab 1mg Q4W Compared With That of Participants Treated With Placebo | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to average score across weeks 36, 40 and 44 | 
| Change in WOMAC Physical Function Subscale Scores From Baseline to Week 16 in Participants Treated With Fasinumab 1mg Q4W, Compared With That of Participants Treated With Naproxen | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 16 | 
| Change in WOMAC Physical Function Subscale Scores From Baseline to Week 44 in Participants Treated With Fasinumab 1mg Q4W, Compared With That of Participants Treated With Placebo | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 44 | 
| Change in WOMAC Physical Function Subscale Scores From Baseline to Week 44 in Participants Treated With Fasinumab 1mg Q4W, Compared With That of Participants Treated With Naproxen | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 44 | 
| Change In WOMAC Pain Subscale Scores From Baseline To The Average Score Across Weeks 4, 8, 12 And 16, in Participants Treated With Fasinumab 1mg Q4W Compared With That of Participants Treated With Placebo | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to average score across weeks 4, 8, 12 and 16 | 
| Change in WOMAC Pain Subscale Scores From Baseline To The Average Score Across Weeks 36, 40 And 44 In Participants Treated With Fasinumab 1mg Q4W Compared With That of Participants Treated With Placebo | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to average score across weeks 36, 40 and 44 | 
| Change in the Patient Global Assessment (PGA) Scores From Baseline to Week 16 in Participants Treated With Fasinumab 1mg Q8W Compared With That of Participants Treated With Placebo | The Patient Global Assessment of OA (PGA) is a patient-rated assessment of current disease state on a 5-point Likert scale (1 = very good; 2 = good; 3 = fair; 4 = poor; and 5 = very poor). | Baseline to Week 16 | 
| Change in the PGA Scores From Baseline to Week 16 in Participants Treated With Fasinumab 1 mg Q8W Compared With That of Participants Treated With Naproxen | The Patient Global Assessment of OA (PGA) is a patient-rated assessment of current disease state on a 5-point Likert scale (1 = very good; 2 = good; 3 = fair; 4 = poor; and 5 = very poor). | Baseline to Week 16 | 
| Change In The PGA Scores From Baseline To Week 44 In Participants Treated With Fasinumab 1mg Q8W Compared With That Of Participants Treated With Placebo | The Patient Global Assessment of OA (PGA) is a patient-rated assessment of current disease state on a 5-point Likert scale (1 = very good; 2 = good; 3 = fair; 4 = poor; and 5 = very poor). | Baseline to Week 44 | 
| Change in WOMAC Pain Subscale Scores From Baseline to Week 16 In Participants Treated With Fasinumab 1mg Q8W, Compared With That of Participants Treated With Naproxen | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 16 | 
| Change in WOMAC Pain Subscale Scores From Baseline to Week 44 in Participants Treated With Fasinumab 1mg Q8W, Compared With That of Participants Treated With Placebo | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 44 | 
| Change in WOMAC Physical Function Subscale Scores From Baseline to the Average Score Across Weeks 4, 8, 12 and 16, in Participants Treated With Fasinumab 1 mg Q8W Compared With That of Participants Treated With Placebo | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to average score across weeks 4, 8, 12 and 16 | 
| Change in WOMAC Physical Function Subscale Scores From Baseline to the Average Score Across Weeks 36, 40 and 44 in Participants Treated With Fasinumab 1mg Q8W Compared With That of Participants Treated With Placebo | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to average score across weeks 36, 40 and 44 | 
| Change in WOMAC Physical Function Subscale Scores From Baseline to Week 16 in Participants Treated With Fasinumab 1mg Q8W, Compared With That of Participants Treated With Naproxen | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 16 | 
| Change in WOMAC Physical Function Subscale Scores From Baseline to Week 44 in Participants Treated With Fasinumab 1mg Q8W, Compared With That of Participants Treated With Placebo | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 44 | 
| Change In WOMAC Pain Subscale Scores From Baseline To The Average Score Across Weeks 4, 8, 12 And 16, in Participants Treated With Fasinumab 1mg Q8W Compared With That of Participants Treated With Placebo | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to average score across weeks 4, 8, 12 and 16 | 
| Percentage Of Participants Treated With Fasinumab 1mg Q8W, Compared With That of Participants Treated With Placebo, Who Had A Response At Week 16, With Response Defined As An Improvement By ≥30% In The WOMAC Pain Subscale Scores | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 16 | 
| Change in WOMAC Pain Subscale Scores From Baseline To The Average Score Across Weeks 36, 40 And 44 In Participants Treated With Fasinumab 1mg Q8W Compared With That of Participants Treated With Placebo | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to average score across weeks 36, 40 and 44 | 
| Number of Participants With Adjudicated Arthropathy (AA) (as Confirmed by Adjudication) - Year 1 |  | Baseline to Week 52 | 
| Number of Participants With AA (as Confirmed by Adjudication) - Year 2 |  | First dose of study drug in Year 2 through week 104E | 
| Number of Participants With AA (as Confirmed by Adjudication) - Year 1 and Year 2 |  | Day 1 through week 104E (Extension) | 
| Number of Participants With Destructive Arthropathy (DA) (as Confirmed by Adjudication) - Year 1 |  | Baseline to Week 52 | 
| Number of Participants With DA (as Confirmed by Adjudication) - Year 2 |  | First dose of study drug in Year 2 through week 104E | 
| Number of Participants With DA (as Confirmed by Adjudication) - Year 1 and Year 2 |  | Day 1 through week 104E | 
| Number of Treatment Emergent Adverse Events (TEAEs) - Year 1 |  | Baseline to Week 52 | 
| Number of TEAEs - Year 2 |  | First dose of study drug in Year 2 through week 104E | 
| Number of TEAEs - Year 1 and Year 2 |  | Day 1 through week 104E | 
| Number of Participants With at Least 1 Sympathetic Nervous System (SNS) Dysfunction Adverse Event of Special Interest (AESI) - Year 1 |  | Baseline to Week 52 | 
| Number of Participants With at Least 1 Sympathetic Nervous System (SNS) Dysfunction Adverse Event of Special Interest (AESI) - Year 2 |  | First dose of study drug in Year 2 through week 104E | 
| Number of Participants With at Least 1 Sympathetic Nervous System (SNS) Dysfunction Adverse Event of Special Interest (AESI) - Year 1 and Year 2 |  | Day 1 through week 104E | 
| Number of Participants With at Least 1 Peripheral Sensory Neuropathy AESI That Require a Neurology or Other Specialty Consultation - Year 1 |  | Baseline to Week 52 | 
| Number of Participants With at Least 1 Peripheral Sensory Neuropathy AESI That Require a Neurology or Other Specialty Consultation - Year 2 |  | First dose of study drug in Year 2 through week 104E | 
| Number of Participants With at Least 1 Peripheral Sensory Neuropathy AESI That Require a Neurology or Other Specialty Consultation - Year 1 and Year 2 |  | Day 1 through week 104E | 
| Number of Participants With Any Type of All-Cause Joint Replacement (JR) in Year 1 |  | Baseline to Week 52 | 
| Number of Participants With Any Type of All-Cause JR in Year 2 |  | First dose of study drug in Year 2 through week 104E | 
| Number of Participants With Any Type of All-Cause Joint Replacement (JR) - Year 1 and Year 2 |  | Day 1 through week 104E |