An Exploratory Phase 2, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Treatment Effect of Pentosan Polysulfate Sodium Compared with Placebo on Synovial Fluid Biomarkers in Participants with Knee Osteoarthritis Pain

INTERVENTION: Participants will receive a single subcutaneous(SC) dose of Pentosan Polysulfate Sodium (PPS) at 2 mg/kg twice weekly for a total of 6 weeks. Participants will visit the clinical trial centre twice weekly for 6 weeks for treatment injections. For the remaining doses, participants will attend the clinical trial centre for pre‐dose assessment, dosing, and post‐dosing assessment as outpatients. Patients adherence to visits will be by reminder phone calls, emails and texts. CONDITION: Inflammatory and Immune System ‐ Other inflammatory or immune system disorders Knee Osteoarthritis; ; Knee Osteoarthritis Musculoskeletal ‐ Osteoarthritis Musculoskeletal ‐ Other muscular and skeletal disorders PRIMARY OUTCOME: To evaluate the effect of PPS on synovial fluid biomarkers associated with inflammation in participants with knee osteoarthritis (OA) pain. (Method of assessment is via synovial fluid biopsy).[Change from Baseline at Day 56 in one or more synovial fluid biomarkers, including but not limited to cartilage oligomeric matrix protein (COMP), C terminal telopeptide (CTX) ‐II, NGF, interleukin (IL) ‐1ß, TNFa, IL‐6, a disintegrin and metalloproteinase with thrombospondin motif 5 (ADAMTS‐5), ARGS (aggrecan cleavage fragments, tissue inhibitor matrix metalloproteinase 1 (TIMP‐1), CTX‐I, and type II collagen (C2C). Synovial fluid biomarker samples will be taken at Baseline and Day 56.] To evaluate the effect of PPS on synovial fluid biomarkers associated with Osteoarthritis (OA) disease progression in participants with knee OA pain. . (Method of assessment is via synovial fluid biopsy).[Change from Baseline at Day 56 in one or more synovial fluid biomarkers, including but not limited to cartilage oligomeric matrix protein (COMP), C terminal telopeptide (CTX) ‐II, NGF, interleukin (IL) ‐1ß, TNFa, IL‐6, a disintegrin and metalloproteinase with thrombospondin motif 5 (ADAMTS‐5), ARGS (aggrecan cleavage fragments, tissue inhibitor matrix metalloproteinase 1 (TIMP‐1), CTX‐I, and type II collagen (C2C). Synovial fluid biomarker samples will be taken at Baseline and Day 56 Method of assessment is testing for biomarkers is by synovial fluid biopsy.] ; Improvement in function of greater than or equal to 25% and greater than or equal to 50% as assessed by the average functional subscale score of the WOMAC® NRS 3.1 Index from Baseline at Days 11, 25, 39, 56, 84, 112, 140, and 168. ; ] To evaluate the effect of PPS on change in pain in participants with knee OA.[Change from Baseline at Days 11, 25, 39, 56, 84, 112, 140, and 168 in knee pain as assessed by the average pain subscale score of the WOMAC® NRS 3.1 Index. ; Reduction in knee pain of greater than or equal to 25% and greater than or equal to 50% as assessed by the average pain subscale score of the WOMAC® NRS 3.1 Index at Days 11, 25, 39, 56, 84, 112, 140, and 168. ; Number of discontinuations for TEAE Day 1 to Day 168. ; Treatment‐emergent clinical laboratory abnormalities Day 1 to Day 168. ; Number of PPS‐treated participants with detection of ADA in serum Day 1 to Day 168. ; ] INCLUSION CRITERIA: Subjects with a clinical diagnosis of osteoarthritis in one or both knees and a radiographic diagnosis of knee osteoarthritis showing a Kellgren‐Lawrence score 2, 3 or 4 Symptomatic pain for at least 6 months preceding screening Males and females aged greater than or equal to 18 years, who are willing and able to comply with study requirements Subjects must be able to provide written informed consent Body Mass Index (BMI) of 18 to 35.0 kg/m2 inclusive Females of non child‐bearing potential or females and males willing to comply with medically acceptable contraceptive requirements of the study Additional inclusion criteria apply. SECONDARY OUTCOME: To evaluate the effect of PPS 6 months after initiation of treatment on synovial fluid biomarkers associated with inflammation in participants with knee OA pain. Method of assessment is testing for biomarkers in synovial fluid.[Change from Baseline at Day 168 in synovial fluid biomarkers, including but not limited to COMP, CTX‐II, NGF, IL‐1ß, TNFa, IL‐6, ADAMTS‐5, ARGS (aggrecan cleavage fragments), TIMP‐1, CTX‐I, and C2C Synovial fluid biomarker samples will be taken at Baseline and Day 168.] To evaluate the effect of PPS 6 months after initiation of treatment on synovial fluid biomarkers associated with OA disease progression in participants with knee OA pain. Method of assessment is testing for biomarkers in synovial fluid.[Change from Baseline at Day 168 in synovial fluid biomarkers, including but not limited to COMP, CTX‐II, NGF, IL‐1ß, TNFa, IL‐6, ADAMTS‐5, ARGS (aggrecan cleavage fragments), TIMP‐1, CTX‐I, and C2C Synovial fluid biomarker samples will be taken at Baseline and Day 168..] To evaluate the effect of PPS on change in function in participants with knee OA pain.[Change from Baseline at Days 11, 25, 39, 56, 84, 112, 140, and 168 in function as assessed by the average functional subscale score of the WOMAC® NRS 3.1 Index. ; ] To evaluate the effect of PPS on change in stiffness in participants with knee OA pain.[Change from Baseline at Days 11, 25, 39, 56, 84, 112, 140, and 168 in knee stiffness as assessed by the average stiffness subscale score of the WOMAC® NRS 3.1 Index.] To evaluate the effect of PPS on consumption of rescue medication in participants with knee OA pain. Rescue medication will be collected electronically via a rescue medication log.[Number of days of rescue medication used from Day 1 to Day 168] To evaluate the effect of PPS on quality of life in participants with knee OA pain.[PGIC scores at Days 11, 25, 39, 56, 84, 112, 140, and 168.] To evaluate the effect of PPS on serum biomarkers associated with inflammation in participants with knee OA pain. (Assessed blood serum sample).[Change from Baseline at Days 56 and 168 in serum biomarkers, including but not limited to, COMP, CTX‐II, ADAMTS‐5, ARGS (aggrecan cleavage fragments), TIMP‐1, CTX‐I, and C2C] To evaluate the effect of PPS on serum biomarkers associated with OA disease progression in participants with knee OA pain. (Assessed by blood serum sample).[Change from Baseline at Days 56 and 168 in serum biomarkers, including but not limited to, COMP, CTX‐II, ADAMTS‐5, ARGS (aggrecan cleavage fragments), TIMP‐1, CTX‐I, and C2C] To evaluate the effect of PPS on urine biomarkers associated with inflammation in participants with knee OA pain.[Change from baseline at Days 56 and 168 in urine biomarkers, including but not limited to CTX‐II] To evaluate the effect of PPS on urine biomarkers associated with OA disease progression in participants with knee OA pain.[Change from baseline at Days 56 and 168 in urine biomarkers, including but not limited to CTX‐II] To evaluate the safety and tolerability of PPS in participants with knee OA pain.[Incidence of Treatment Emergent Adverse Events (TEAEs), including serious adverse events (SAEs) Day 1 to Day 168.