A Phase 2, Two-Part, Randomized, Double-Blind, Active-Controlled Study to Assess the Safety and Tolerability of Enekinragene Inzadenovec (PCRX-201) in Subjects With Painful Osteoarthritis of the Knee
The goal of this clinical trial is to learn if a single knee injection of different doses (Dose A and Dose B) of an investigation product PCRX-201, following steroid pretreatment, is safe and tolerable in male of female patients 45 to 80 years old with osteoarthritis of the knee. It will also learn how the body reacts to the PCRX-201 injection and how effective the treatment is. Researchers will compare Dose A and Dose B of PCRX-201 versus placebo from Week 1 through Week 52 to assess adverse events. Researchers will also explore how PCRX-201 may impact knee pain and joint function over time. Participants will be asked to * Visit the clinic for pretreatment and drug administration * Visit the clinic for checkups and tests: 1. Screening through Week 52: intially weekly, bi-weekly, later monthly 2. Week 53 through Week 260 (Year 5): 8 visits throughout the period
• Subjects must be willing and able to comply with the study procedures and visit schedule 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 received 2 or more failed 2 or more therapies: Restricted physical activity as per Osteoarthritis Research Society International (OARSI) core level recommendation, ie, structured land-based exercise (this may include physical therapy), and failure of an 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 the intended injection site area are free of any signs of local or joint infection at Baseline.
• Subjects must have an index knee Average Daily Knee Pain (NRS) between ≥5.0 and ≤9.0 at Screening and Baseline.
• Sexually active subjects of child-bearing potential (SOCBP) and their partners must agree to use effective birth control while in the study
• Subjects must have active synovitis in the index knee as determined by ultrasound Doppler (Part A only) For Part B, participants must have active synovitis in the index knee as determined by contrast-enhanced MRI.
• Subjects must exhibit American College of Rheumatology Criteria (clinical and radiological) for osteoarthritis as follows:
‣ Knee pain
⁃ 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 (Part A) or K-L Grade 2 or 3 (Part B) in the index knee based on X-rays performed during Screening and confirmed by trained radiographers at a central facility before enrollment
• Subjects need to show the presence of moderate or severe synovitis based on 11-point synovitis score using contrast-enhanced MRI (Part A). For Part B, participants need to show the presence of synovitis ≥5 on the Guermazi synovitis scoring scale using contrast-enhanced MRI to be enrolled.