A Study to Assess Safety and Tolerability of PCRX-201 in Subjects With Painful Osteoarthritis of the Knee

Inclusion Criteria:

• Subjects must be willing and able to comply with the study procedures and visitschedule and able to follow verbal and written instructions.

• Subjects must be male or female and 45 to 80 years old, inclusive, at Screening.

• Subjects must exhibit symptoms associated with osteoarthritis of the index knee for ≥12 months before Screening (subject self-reporting is acceptable).

• Subjects must have index knee pain for >15 days over the last month before Screening (subject self-reporting is acceptable).

• Subjects must have failed 2 or more therapies: Restricted physical activity as perOsteoarthritis Research Society International (OARSI) core level recommendation, ie, "structured land-based exercise" (this may include physical therapy), and failure ofan additional type of conservative therapy for OA of the index knee, eg,nonselective NSAIDs or COX-2 inhibitors, in the past 12 months.

• Subjects must have a body mass index (BMI) ≤40 kg/m2 at Screening.

• Subjects must have an index knee examination indicating the index knee and theintended injection site area are free of any signs of local or joint infection atBaseline.

• Subjects must have an index knee Average Daily Knee Pain (NRS) between ≥5.0 and ≤9.0at Screening and Baseline.

• Sexually active subjects of child-bearing potential (SOCBP) and their partners mustagree to use effective birth control while in the study

• Subjects must have active synovitis in the index knee as determined by ultrasoundDoppler.

• Subjects must exhibit American College of Rheumatology Criteria (clinical andradiological) for osteoarthritis as follows:

1. Knee pain

2. At least 1 of the following: i. Age >50 years ii. Morning stiffness <30 minutes iii. Crepitus on knee motion c.Osteophytes

• Subjects must have K-L Grade 2, 3, or 4 in the index knee based on X-rays performedduring Screening and confirmed by trained radiographers at a central facility beforeenrollment

• Subjects need to show the presence of moderate or severe synovitis based on 11-pointsynovitis score using contrast-enhanced MRI

Exclusion Criteria:

• Subjects have any current or prior diagnosis of autoimmune connective tissuedisorders, secondary OA conditions, benign synovial tumors, gout/pseudogout,reactive arthritis, RA, psoriatic arthritis, ankylosing spondylitis, or arthritisassociated with inflammatory bowel disease.

• Subjects have any active systemic or local infection, including infection of theindex knee

• Subjects are unable to undergo MRI with contrast MRI

• Subjects with X-ray or MRI exclusionary events

• Subjects have an unstable index knee joint (eg, torn anterior cruciate ligament)within 12 months of Screening

• Subjects have used any approved or investigational IA drug/biologic in index kneewithin 6 months of Screening (eg, hyaluronic acid, platelet rich plasma, stem cells,prolotherapy, and amniotic fluid injection)

• Subjects are receiving or have received any gene therapy treatment (eg, IL-1Ra) inthe past 3 years

• Subjects have used IA steroids ≤3 months before screening

Other protocol-defined criteria apply