• Volunteers will be included in the study only if they satisfy all the following criteria:

• Able to read, understand, sign, and date the subject informed consent.

• Have given written informed consent before any study-related activities are carried out and are able to understand the nature and purpose of the trial, including possible risks and adverse effects.

• Adult males and females, 50 to 80 years of age (inclusive) at Screening.

• Body weight less than 136 kgs (300 lbs) at Screening.

• Except for OA, subject is medically healthy (in the opinion of the PI), as determined by prestudy medical history, and without clinically significant abnormalities including:

∙ Clinically relevant findings on physical examination that would preclude trial compliance.

‣ Heart rate \<40 BPM or \>100 BPM after 5 minutes rest in supine or semi-supine position.

‣ Body temperature \<95.9°F or \>99.8°F. Note: The above assessments may be repeated, if abnormal values are recorded in the first instance, at the discretion of the Investigator (or delegate).

• Available X-Ray of target knee obtained within 12 months prior to Screening with radiographic evidence of osteoarthritis in the medial and/or lateral tibio-femoral compartment; KL grading is not required.

• Clinical diagnosis of knee OA with at least 2 of the 4 following signs/symptoms in the target knee, and in the absence of palpable warmth suggesting synovitis or infection:

‣ Crepitus on knee extension

⁃ Bony tenderness

⁃ Bony enlargement

⁃ Morning stiffness in target knee \<30 minutes

• Stability of Cruciate and collateral ligaments as defined by clinical examination (e.g. tests such as Lachman, pivot shift, posterior drawer, posterior sag, valgus and Varus stress).

• Results of the KOOS Knee Survey Screening Questionnaire performed at Screening for the target knee that indicate either: moderate or greater difficulty in at least 5 of 17 questions (A1-17) in the Function, daily living subsection; or a total score of at least 20/68 in that subsection.

⁃ Results of the KOOS Knee Survey Screening Questionnaire performed at Screening that indicate moderate or greater pain on question P6 pain going up or down stairs in the target knee.

⁃ Willing to use only acetaminophen (Tylenol® or equivalent), hydrocodone, orhydrocodone/acetaminophen (e.g., Norco® or equivalent) for breakthrough pain during the4-week injection period. The maximum dose of acetaminophen from all sources must not exceed 4000 mg/day.

⁃ Willing NOT to use non-steroidal anti-inflammatory drugs such as aspirin, ibuprofen (Motrin® or equivalent), or naproxen (Aleve® or equivalent) during the 4-week injection period.

⁃ Willing NOT to use approved or investigational IA products for knee OA for the duration of participation in the study.

⁃ If using GLP-1 medications such as Wegovy® or similar, must be on a stable dose for at least 2 months prior to Screening.

⁃ Female subjects of childbearing potential who are sexually active (non-abstinent) must agree to and comply with using 2 highly effective methods of birth control (oral contraceptive implant, injectable or indwelling intrauterine device, condom with spermicide or sexual abstinence) while participating in the study. Male participants must agree to use a barrier contraception method to prevent pregnancy, and agree not to donate sperm from the time of the first injection through the end of the study.

⁃ Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.

⁃ MRI Screening: Tibio-femoral osteoarthritis with MRI based femoral B-score at Screening of 0.5 or greater in at least one knee as determined by central analysis.