ZILRETTA in Subjects with Shoulder Osteoarthritis

Inclusion Criteria:

1. Written informed consent has been obtained prior to initiating any study-specificprocedures.

2. Willingness and ability to comply with the study procedures and visit schedules andability to follow verbal and written instructions, including eDiary questionnairecompletion requirements.

3. Subjects 50 to 80 years of age, inclusive, on the day of consent.

4. Body Mass Index (BMI) ≤40 kg/m2.

5. Symptoms (including pain) associated with OA of the index shoulder for ≥3 monthsprior to Screening Visit (subject self-report is acceptable).

6. Shoulder pain due to OA for >15 days over the last month (as reported by thesubject).

7. Grade 2 or 3 OA in the index glenohumeral joint based on the Samilson-Prietoclassification system as confirmed by X-ray (axillary view and trueanterior-posterior view) taken at, or within 6 months of, the Screening Visit andread by the central reader.

8. Average daily mean pain score ≥4.0 and ≤9.0 in index shoulder (0-10 numeric ratingscale [NRS]) using the average daily ratings for at least 4 out of the 7 days priorto Baseline/Day 1.

9. Average Shoulder Pain and Disability Index (SPADI) pain score ≥5.0 and ≤9.0 in indexshoulder prior to Baseline/Day 1.

10. Willingness to abstain from use of protocol-specified restricted medications andtherapies during the study.

11. Sexually active males or females of childbearing potential must agree to use ahighly effective method of contraception throughout the duration of the study.Females of childbearing potential are defined as females who are not surgicallysterile or postmenopausal (defined as 12 consecutive months with no menses withoutan alternative medical cause) as documented in medical history. Highly effectivemethods of contraception include abstinence; oral, injected, or implanted hormonalmethods of contraception; intrauterine device or intrauterine system; condom orocclusive cap (diaphragm or cervical/vault caps) with spermicidalfoam/gel/film/cream/suppository; or monogamous intercourse with a partner who issurgically sterile (post-vasectomy, -hysterectomy, or -tubal ligation).

Exclusion Criteria:

Disease-related criteria

1. Subjects who cannot washout of prohibited medications (eg, opioids, otheranalgesics, and tetrahydrocannabinol (THC) and cannabidiol (CBD) containingproducts) or restricted medications.

2. Has symptomatic arthritis in other joints of the index shoulder (eg,acromioclavicular joint, sternoclavicular joint, or scapulothoracic joint), which isthe primary source of pain in the opinion of the Investigator.

3. Has symptomatic rotator cuff pathology by physical examination or evidence of cufftear arthropathy by radiograph.

4. Has clinical symptomatic chronic bilateral shoulder pain (any condition causing painin the non- index shoulder).

5. Has a subchondral bone insufficiency fracture or humeral head necrosis/collapse (including bone infarct) in the index shoulder based on X-ray used for studyqualification.

6. Has a prior ipsilateral proximal humerus fracture or scapula fracture to the indexshoulder within 2 years of Screening Visit.

7. Has been diagnosed with adhesive capsulitis ("frozen shoulder") in the indexshoulder, within 1 year of the Screening Visit.

8. Has a previous shoulder injury (eg, dislocation or clavicle fracture) in the indexshoulder which resulted in functional limitation ≥1 month prior to the ScreeningVisit.

9. Prior surgery on the index shoulder (less than 5 years), either open orarthroscopic. Should not have any retained hardware.

10. Has an index shoulder with major dysplasia or congenital abnormality,osteochondritis dissecans, acromegaly, ochronosis, hemochromatosis, Wilson'sdisease, primary osteochondromatosis, chondrolysis from a pain pump, or a history ofavascular necrosis with secondary OA.

11. Has current or history of infection (eg, osteomyelitis) in the index shoulder orcurrent skin infection at injection site.

12. Has any concurrent chronic pain condition within 1 month prior to the ScreeningVisit (subject self- report acceptable), including but not limited to, cervicalspine pain or conditions causing radicular pain or peripheral nerveinjury/entrapment (eg, brachial plexus injury or suprascapular nerve entrapment);diabetic neuropathy; post-herpetic neuralgia; post-stroke pain; or fibromyalgia thatmay affect sensation of the index shoulder.

13. painDETECT Questionnaire (PD-Q) score >18 during Screening Visit.

14. History or current evidence of reactive arthritis, rheumatoid arthritis, psoriaticarthritis, ankylosing spondylitis, or arthritis associated with inflammatory boweldisease, systemic lupus erythematosus, or calcium pyrophosphate dihydrate crystaldeposition (CPPD), gout, or other autoimmune diseases.

15. Any planned surgeries in the upper limbs and/or cervical spine during the studyperiod, or any other surgery during the study period that would require use of arestricted medication. Previous or concomitant treatment-related criteria

16. Presence of surgical hardware or other foreign body due to open or arthroscopiccartilage transplant or bone grafting procedures in the index shoulder.

17. Use of muscle relaxants (eg, cyclobenzaprine, tetrazepam, and diazepam) and topicaltherapies (eg, NSAIDs, CBD oil, capsaicin, lidocaine patches, or other localtreatments) applied to the index shoulder.

18. The use corticosteroids as follows:

• IA corticosteroid in the index shoulder within 3 months of Screening Visit.

• Intrabursal and intratendinous corticosteroids in the index shoulder within 6months of Screening Visit.

• Intravenous (IV), Intramuscular (IM), or epidural corticosteroids within 6months of Screening.

• Oral corticosteroids within 1 month of Screening.

19. IA treatment of index shoulder with any of the following agents within 6 months ofScreening: hyaluronic acid (investigational or marketed) or any biologic agent (eg,platelet rich plasma [PRP] injection, stem cells, prolotherapy, and amnioticfluid-derived product).

20. Significant changes with regard to physical activity, physical therapy, or lifestylewithin 1 month of the Screening Visit, or any planned changes throughout theduration of the study.

21. Use of selective serotonin/norepinephrine reuptake inhibitors (SSRIs/SNRIs) (eg,fluoxetine, fluvoxamine, citalopram, escitalopram, sertraline, duloxetine, andvenlafaxine, milnacipran) if the dose is not stable for at least 3 months prior toScreening Visit and must remain stable throughout the study.

22. Any treatment with acupuncture and/or transcutaneous electrical nerve stimulation (TENS) within 3 months of Screening Visit. Subject-related criteria

23. Females who are pregnant or nursing or plan to become pregnant within 12 monthsafter dosing; men whose partner plans to conceive within 12 months after dosing.

24. Subjects with clinically relevant level of pain catastrophizing defined as PainCatastrophizing Scale (PCS) score of ≥30 at Screening Visit.

25. Known or suspected hypersensitivity to any form of triamcinolone or poly (lactic-co-glycolic) acid (PLGA).

26. Laboratory evidence of infection with human immunodeficiency virus (HIV), positivetest for hepatitis B surface antigen (HBsAg), or positive serology for hepatitis Cvirus (HCV) with positive test for HCV ribonucleic acid (RNA) on recent testing.

27. A medical history suggesting the subject will or is likely to require a course ofsystemic corticosteroids during the study.

28. History or evidence of active or latent systemic fungal or mycobacterial infection (including tuberculosis) or of ocular herpes simplex.

29. History of sarcoidosis, amyloidosis or active Cushing's syndrome.

30. Use of immunomodulators, immunosuppressives, or chemotherapeutic agents within 5years of Screening.

31. Active or history of malignancy within 5 years of Screening, with the exception ofresected basal cell carcinoma, squamous cell carcinoma of the skin, or effectivelymanaged cervical carcinoma.

32. History of radiation treatment involving the index shoulder girdle.

33. Active substance abuse (drugs or alcohol) or history of substance abuse within thepast 12 months of Screening.

34. Has received a live vaccine within 3 months of Baseline/Day 1.

35. Has received vaccination within 1 week prior to the Screening Visit and localinjection pain has not resolved.

36. Use of any other investigational drug, biologic, or device within 3 months ofScreening Visit.

37. Any bacterial or viral infection requiring IV antibiotics within 4 weeks ofBaseline/Day 1 or oral antibiotics within 2 weeks of Baseline/Day 1.

38. Any other clinically significant acute or chronic medical conditions (eg, poorlycontrolled diabetes with hemoglobin A1c [HbA1c] of greater than 9.5%) that, in thejudgment of the Investigator, could compromise subject safety, preclude the use ofan IA corticosteroid, limit the subject's ability to complete the study, orcompromise the objectives of the study.

39. Subjects contraindicated to the use of acetaminophen/paracetamol (allowed rescuepain medicine) per National Product Labeling and Investigator's judgment.

40. Investigator or any subinvestigator, research assistant, pharmacist, studycoordinator, or other staff or relative thereof directly involved in the conduct ofthe study.