• Subject is age ≥ 21 and ≤ 80 years.

• Subject has a diagnosis of primary OA of the target knee (as per American College of Rheumatology clinical and radiological criteria) with OA symptoms (as reported by the subject) that have been present for at least 6 months prior to Screening.

• Subject has Grade 2 or 3 OA of the target knee on the Kellgren Lawrence (KL) grading scale as evaluated by central reading of screening X-ray.

• Subject is willing and able to provide informed consent and participate in all procedures and follow-up evaluations necessary to complete the study.

• Subject must have a WOMAC pain score ≥ 4 and ≤ 9 out of 10 in target knee, at screening and baseline.

• Subject must have tried and failed to adequately respond to 2 knee OA standard of care (SOC) therapies, including at least one pharmacological treatment, for a minimum of 3 months. SOC for knee OA include non-pharmacological (exercise, weight loss, knee braces, cane) and pharmacological treatments (topical nonsteroidal anti-inflammatory drugs \[NSAIDs\], oral NSAIDs, and intra-articular corticosteroids).

• Subject must be willing to discontinue all current pain medications (including but not limited to oral, topical, intra-articular) during the duration of the study except for acetaminophen (paracetamol) which will be allowed as rescue, except as noted in inclusion criterion 10 below. Limited use of NSAIDS will be permitted at the discretion of the investigator for post injection pain only.

• Subject must have a WOMAC pain subscale score in contralateral knee less than 4 out of 10, at screening and baseline visits.

• Subject who is identified as having taking analgesics at their initial screening visit 1a must be willing to abstain from analgesics for a washout period of 5 half-lives of the analgesic plus 48 hours and return for screening visit 1b where WOMAC pain can be collected analgesic-free.

⁃ Subject must be willing to abstain from use of rescue medication (acetaminophen/paracetamol) for at least 72 hours prior to all study visits subsequent to screening.

⁃ For male subjects:

∙ Subject must agree to use highly effective contraception throughout the study.

‣ Subject must agree not to donate sperm during the study.

⁃ For female subjects:

∙ Subject is surgically sterile; or

‣ Has been amenorrheic for at least 1 year and is over the age of 55 years; or

‣ Has a negative urine pregnancy test and agrees to use acceptable contraceptive measures (e.g. hormonal contraceptives, barriers with spermicide, intrauterine device or vasectomized partner) from the time of informed consent through the end of the study; and

‣ Must commit to the use of highly effective form of birth control from the time of informed consent through the end of the study.

⁃ Subject must have vital signs within the following ranges at the screening visit and at the baseline visit before investigational product administration:

∙ Systolic blood pressure ≤140 and ≥90 mmHg,

‣ Diastolic blood pressure ≤90 and ≥60 mmHg,

‣ Heart rate \<100 and \>60 bpm,

‣ Temperature: normal,

‣ Respiratory rate \<20 and \>12 /min.