| Eligibility |
Inclusion Criteria:
1. Signed Informed Consent form (ICF).
2. Male or female participants between =40 and =80 years of age.
3. BMI =40 kg/m2.
4. The ability to utilize the eDiary device provided by study sites.
5. History of knee pain on most days for at least 3 months prior to Screening
6. Confirmation of OA of the knee
1. Radiographs of both knees with a Posterior-Anterior, Fixed-flexion view taken
during the Screening Period.
2. American College of Rheumatology (ACR) clinical and radiographic diagnostic
criteria.
7. Evidence of knee OA with a KL grade =2, determined through central reading.
8. Target Knee must have a score of =20 out of 50 on the WOMAC pain subscale during
Screening and at Randomization
9. The Baseline (NRS) Pain score will be derived from the last seven days of the Diary
Run-In Period and must meet following criteria:
1. Completion of Average Daily (NRS) Pain score on at least 6 of the 7 days.
2. Mean Average Daily (NRS) Pain score must be =4.0 and =9.0
3. Mean Average Daily (NRS) Pain variability must be =1.5
10. If female, not of childbearing potential defined as post-menopausal for at least 1
year, or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or
hysterectomy), or practicing an agreed upon highly effective method of birth control
throughout the study period.
11. If male and sexually active with partner of childbearing potential, willing to agree
to practice a highly effective method of contraception from Visit 2 and at least 3
months after Visit 11 (week 20).
12. Willing to withdraw from any medication for Osteoarthritis including, but not limited
to, Opioids, Non-Steroidal Anti-inflammatories (NSAIDs), COX-2 inhibitors, Topical
medication, and Duloxetine.
13. Participant agrees to take only the allowed Rescue Medications from the start of the
Diary Run-In Period through study completion (maximum 4000 mg paracetamol per day).
Exclusion Criteria:
1. Presence of OA of other major joints (including but not limited to nontarget knee)
that could interfere with assessment of pain due to OA of the target knee, in the
opinion of the investigator.
2. Current comorbid condition, other than OA, known to be significantly associated with
arthritis or joint pathology, including but not necessarily limited to autoimmune
disease with significant joint involvement (e.g., Rheumatoid Arthritis or Paget's
disease; Seronegative Spondyloarthropathies (e.g. Ankylosing Spondylitis, Psoriasis
arthritis, Reactive arthritis); or other systemic disease involving the target knee
(including endocrinopathies).
3. The following conditions should be excluded: Known presence of rapidly Progressive
Osteoarthritis (RPOA), primary osteonecrosis (including spontaneous osteonecrosis of
the knee), subchondral insufficiency fractures (SIF), avascular necrosis, osteoporotic
fractures, atrophic OA, excessive malalignment of the knee (anatomical axis angle
greater than 10 degrees), pathological fractures, or stress fracture or reaction,
vertical tear of the posterior meniscal root, or large or extensive subchondral cysts,
or target knee anserine or patellar bursitis of clinical relevance
4. Hip dislocation and congenital hip dysplasia with degenerative joint disease should be
excluded.
5. History of gout with recent (< 6 months) pain flares and uncontrolled uric acid
levels. Participants with a history or diagnosis of pseudogout (calcium pyrophosphate
dihydrate crystal deposition disease) can enroll if there has not been a flare within
6 months prior to screening and use of NSAIDs is not required for management of this
condition.
6. Presence of neuropathic pain deemed likely to interfere with trial endpoints, complex
regional pain syndrome, or chronic widespread pain syndromes e.g., fibromyalgia.
7. History of significant trauma (e.g., intra-articular fracture) or surgery (excluding
injection therapies and arthroscopy) to a knee, hip, or shoulder within the previous 1
year
8. Planned major surgery or other major invasive procedures while participating in the
study.
9. Surgery or stent placement for coronary artery disease in the six months prior to
screening .
10. Nondiagnostic arthroscopy performed on the target knee joint within 180 days prior to
Screening; or diagnostic arthroscopy performed on the target knee joint within 90 days
prior to Screening.
11. Intraarticular injection therapies to the target knee joint within 12 weeks prior to
Screening, or to any non-target joint within 6 weeks prior to Screening.
12. Participants likely to be deemed unfit for joint replacement surgery due to
concomitant illness, in the investigator opinion.
13. Opioid use, including Tramadol, of 4 or more instances per week over the month prior
to Screening.
14. Known history of hypersensitivity to monoclonal antibodies.
15. Presence of any medical condition or unstable health status that, in the judgment of
the investigator, might adversely impact the safety of the participant.
16. Signs and symptoms of significant cardiac disease, including but not limited to
established ischemic heart disease, peripheral arterial disease and /or
cerebrovascular disease (unstable angina, myocardial infarction, cardiovascular
thrombotic events, transient ischemic attacks, and stroke in the six months prior to
screening)
17. Active malignancy or history of malignancy within the past 5 years, with exception of
resected and cured basal cell carcinoma and squamous cell carcinoma of the skin.
18. Clinically significant abnormal laboratory parameter(s) and/or ECG parameter(s) during
Screening, that, in the judgment of the Investigator, would preclude the participant
from participation in this study.
19. Participation in other studies involving investigational drug(s) within 30 days (or 90
days for biologics) prior to screening.
20. History of Carpal Tunnel Syndrome with symptoms within one year of Screening or a
Boston Carpal Tunnel Questionnaire (Symptom Severity Scale) mean score =3.
21. A total Symptom Impact score on the Survey of Autonomic Symptoms =3.
22. Pregnant or breast feeding.
23. Previously received any form of anti-NGF
24. Requires walker or wheelchair for mobility (walking stick permitted).
25. Active or historic substance abuse within one year of Screening in the opinion of the
Investigator.
26. Medical history within 5 years of Screening that involves suicidal ideation, suicide
attempt, or increased risk of suicide as assessed by the Investigator.
27. Presence of any contraindication to MRI
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