A Study to Investigate the Treatment Effect of Subcutaneous Injections of Pentosan Polysulfate Sodium Compared With Placebo in Adult Participants With Knee Osteoarthritis Pain.

May 6, 2026 updated by: Paradigm Biopharmaceuticals Ltd.

A Phase 3, Randomised, Double-Blind, Placebo-Controlled Multi-Centre Study to Evaluate the Treatment Effect of Pentosan Polysulfate Sodium Compared to Placebo in Participants With Knee Osteoarthritis Pain

The purpose of this study is to measure the change in pain and function with subcutaneous injections of pentosan polysulfate sodium (PPS) compared with subcutaneous injections of placebo in participants with knee OA pain.

Study details include:

  • The study duration will be up to 64 weeks.
  • The treatment duration will be 6 weeks.
  • The visit frequency will be twice weekly during treatment.
  • The visit/contact frequency will be every 4-6 weeks during the 52-week Follow-up period.
  • Approximately 466 participants will be enrolled into this study.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a randomised, double-blind, placebo-controlled, multicenter study that will evaluate the dose and treatment effect of PPS in participants with knee OA pain.

Participants will be randomised 1:1 to receive twice-weekly subcutaneous (SC) injections of 2 mg/kg PPS or placebo for 6 weeks.

An interim analysis for a potential early conclusion is planned after approximately 50% of participants complete Day 112.

The primary analysis will be conducted when all participants complete Day 112. A final analysis will be conducted when the last participant reaches Day 404.

The maximum duration for each participant is up to 64 weeks, which includes

  • 7-week Screening Period from Day -45 to Day -1
  • 6-week Treatment Period from Day 1 to Day 39
  • 52-week Follow-up Period from Day 40 to Day 404

Study Type

Interventional

Enrollment (Estimated)

466

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Brookvale, New South Wales, Australia, 2100
        • Recruiting
        • Canopy Clinical Research-Northern Beaches
        • Contact:
        • Principal Investigator:
          • Deon Smith, MD
      • Charlestown, New South Wales, Australia, 2290
        • Recruiting
        • NovaTrials
        • Principal Investigator:
          • Oscar Cumming, MD
        • Contact:
      • Miranda, New South Wales, Australia, 2228
        • Recruiting
        • Canopy Clinical Research - Sutherland Shire
        • Principal Investigator:
          • Karen Kaluhin
        • Contact:
      • Wollongong, New South Wales, Australia, 2500
        • Recruiting
        • Canopy Clinical Research-Wollongong
        • Contact:
        • Principal Investigator:
          • Tess Tonkin, MD
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Recruiting
        • Mater Health Brisbane
        • Contact:
        • Principal Investigator:
          • Paul Griffin, MD
      • Southport, Queensland, Australia, 4222
        • Recruiting
        • Griffith University
        • Contact:
        • Principal Investigator:
          • Marije Dalebout, MD
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Recruiting
        • Royal Adelaide Hospital
        • Contact:
        • Principal Investigator:
          • Guy Ludbrook, MD
      • Stepney, South Australia, Australia, 5069
    • Victoria
      • Altona N., Victoria, Australia, 3025
        • Recruiting
        • Canopy Clinical Research-Altona North
        • Contact:
        • Principal Investigator:
          • Oscar Walsh, MD
      • Box Hill, Victoria, Australia, 3128
        • Recruiting
        • Sportsmed Biologic LTD
        • Contact:
        • Principal Investigator:
          • Phillip Bloom, MD
    • Western Australia
      • Perth, Western Australia, Australia, 6000
        • Recruiting
        • Clinitrials
        • Contact:
        • Principal Investigator:
          • Zachary Nathan
      • Victoria Park, Western Australia, Australia, 6100
        • Recruiting
        • RK Will Pty Ltd
        • Contact:
        • Principal Investigator:
          • Robert Will, MD
  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Hong Kong Centre for Clinical Research
        • Contact:
        • Principal Investigator:
          • Edith Lau
  • Moldova
      • Chisinau, Moldova, MD2025
        • Recruiting
        • PMSI "Timofei Mosneaga" Republican Clinical Hospital
        • Contact:
        • Principal Investigator:
          • Liliana Groppa, MD
      • Chisinau, Moldova, MD2025
        • Recruiting
        • PMSI Institute of Cardiology
        • Contact:
        • Principal Investigator:
          • Minodora Mazur, MD
      • Chisinau, Moldova, MD2068
        • Recruiting
        • PMSI "Sfanta Treime" Municipal Clinical Hospital
        • Contact:
        • Principal Investigator:
          • Serghei Popa, MD
  • United States
    • Arizona
      • Peoria, Arizona, United States, 85381
        • Recruiting
        • Onyx Clinical Research-Peoria
        • Contact:
        • Principal Investigator:
          • Shweta Mehta, MD
      • Tucson, Arizona, United States, 85715
        • Recruiting
        • Del Sol Research Management, LLC
        • Principal Investigator:
          • Vicki Kalen, MD
        • Contact:
    • California
      • Anaheim, California, United States, 92801
        • Recruiting
        • Orange County Research Institute
        • Principal Investigator:
          • Steve Sitar, MD
        • Contact:
      • Cerritos, California, United States, 90703
        • Recruiting
        • Core Healthcare Group
        • Principal Investigator:
          • Francisco Badar, MD
        • Contact:
      • Chula Vista, California, United States, 91910
        • Recruiting
        • Triwest Research Center
        • Principal Investigator:
          • Arthur Mabaquiao, MD
        • Contact:
      • Oceanside, California, United States, 92058
        • Recruiting
        • Seaside Medical Group
        • Contact:
        • Principal Investigator:
          • Paul Lizotte, MD
      • Santa Ana, California, United States, 92703
        • Recruiting
        • Paragon RX Clinical
        • Contact:
        • Principal Investigator:
          • Kelvin Mai, MD
      • Spring Valley, California, United States, 91978
        • Recruiting
        • Encompass Clinical Research
        • Principal Investigator:
          • Hanid Audish, MD
        • Contact:
      • West Hills, California, United States, 91307
        • Recruiting
        • Focus Clinical Research
        • Principal Investigator:
          • Hessam Aazami, MD
        • Contact:
    • Florida
      • Clearwater, Florida, United States, 33765
        • Recruiting
        • Clinical Research of West Florida - Clearwater
        • Principal Investigator:
          • Robert Levin, MD
        • Contact:
      • Cooper City, Florida, United States, 33024
        • Recruiting
        • GNP Research
        • Contact:
        • Principal Investigator:
          • Mark Jaffe, MD
      • Daytona Beach, Florida, United States, 32117
        • Recruiting
        • Arrow Clinical Trials
        • Principal Investigator:
          • David Billmeier, MD
        • Contact:
      • Hialeah, Florida, United States, 33012
        • Recruiting
        • AGA Clinical Trials
        • Principal Investigator:
          • Dario Altamirano, MD
        • Contact:
      • Miami, Florida, United States, 33173
        • Recruiting
        • Well Pharma Medical Research
        • Principal Investigator:
          • Eddie Armas, MD
        • Contact:
      • Miami, Florida, United States, 33122
        • Recruiting
        • Evolution Clinical Trials
        • Principal Investigator:
          • Gilberto Perez, MD
        • Contact:
      • Orlando, Florida, United States, 32806
        • Recruiting
        • K2 Medical Research
        • Contact:
          • Study Coordinator
          • Phone Number: 407-987-3284
          • Email: tba@k2med.com
        • Principal Investigator:
          • Beatriz Colon, MD
      • Port Orange, Florida, United States, 32127
      • Tamarac, Florida, United States, 33321
        • Recruiting
        • Phoenix Clinical Research
        • Principal Investigator:
          • Richard Berkowitz, MD
        • Contact:
      • Winter Park, Florida, United States, 32789
        • Recruiting
        • Conquest Research
        • Principal Investigator:
          • Anand Patel, MD
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611
      • Chicago, Illinois, United States, 60607
        • Recruiting
        • Chicago Clinical Research, Inc
        • Principal Investigator:
          • Dennis Levinson, MD
        • Contact:
          • Study Coordinator
          • Phone Number: Ext 305 312-791-3241
          • Email: Alicia@ccrii.us
    • Maryland
      • Baltimore, Maryland, United States, 21215
        • Recruiting
        • Sinai Hospital of Baltimore
        • Principal Investigator:
          • James Nace, MD
        • Contact:
    • Michigan
      • Farmington Hills, Michigan, United States, 48334
        • Recruiting
        • Profound Research
        • Contact:
        • Principal Investigator:
          • Barry Feldman, MD
      • Flint, Michigan, United States, 48507
        • Recruiting
        • Insight Research Institute
        • Principal Investigator:
          • Vincent Rampersaud, MD
        • Contact:
      • Rochester Hills, Michigan, United States, 48307
        • Recruiting
        • Rochester Medical Group
        • Contact:
        • Principal Investigator:
          • Michael Margolis, MD
      • Troy, Michigan, United States, 48085
        • Recruiting
        • Onyx Clinical Research - Rochester Hills
        • Principal Investigator:
          • Ramkrishna Surendran, MD
        • Contact:
    • Nebraska
      • Lincoln, Nebraska, United States, 68516
        • Recruiting
        • Physician Research Collaboration
        • Principal Investigator:
          • Melvin Churchill, MD
        • Contact:
    • Nevada
      • Las Vegas, Nevada, United States, 89109
        • Recruiting
        • Alpine Healthcare Family Practice
        • Principal Investigator:
          • Robert Kaplan, MD
        • Contact:
    • New York
      • Hartsdale, New York, United States, 10530
        • Recruiting
        • Drug Trials America
        • Contact:
        • Principal Investigator:
          • Michael Gerdis, MD
      • Mineola, New York, United States, 11501
        • Recruiting
        • Groth Pain & Spine - Long Island, NY
        • Contact:
        • Principal Investigator:
          • Mariyam Wasay, MD
      • New York, New York, United States, 10036
        • Recruiting
        • Ima Clinical Research Manhattan
        • Principal Investigator:
          • James Greenwald, MD
        • Contact:
      • Smithtown, New York, United States, 11787
    • Texas
      • Austin, Texas, United States, 78731
        • Recruiting
        • FutureSearch Trials of Neurology
        • Contact:
        • Principal Investigator:
          • Gregory Tempest, MD
      • Dallas, Texas, United States, 75251
        • Recruiting
        • FutureSearch Trials of Dallas
        • Contact:
        • Principal Investigator:
          • Michael Downing, MD
      • Houston, Texas, United States, 77065
        • Recruiting
        • DM Clinical Research
        • Contact:
        • Principal Investigator:
          • Tiffany Huynh, MD
      • Houston, Texas, United States, 77074
        • Recruiting
        • Clinical Trial Network
        • Principal Investigator:
          • Alan Reichman, MD
        • Contact:
      • Houston, Texas, United States, 77017
        • Recruiting
        • Vilo Research Group
        • Contact:
        • Principal Investigator:
          • Luis Zepeda, MD
      • Lewisville, Texas, United States, 75057
      • San Antonio, Texas, United States, 78209
        • Recruiting
        • Quality Research Inc.
        • Principal Investigator:
          • Robert Morin, MD
        • Contact:
    • Utah
      • Ogden, Utah, United States, 84404
        • Recruiting
        • Rio Clinical Trials
        • Contact:
        • Principal Investigator:
          • Stephen Bruce, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Participant must be ≥18 years of age inclusive, at the time of signing the informed consent.
  2. Clinical diagnosis of OA in the index knee by American College of Rheumatology 1986 criteria.
  3. Radiographic diagnosis (confirmed by radiologist) of knee OA classified K-L grade 2, 3, or 4 on standing anterior-posterior X-ray of the index knee.
  4. Participant is unresponsive for at least 6 months preceding Screening to any two combinations of OA therapies (one from each A and B) within the last 12 months that include: A.) conservative non-pharmacologic therapy (exercise, weight loss, physical therapy) or simple analgesics (e.g., acetaminophen) and B.) pharmacological treatment (topical or oral NSAIDs [or cyclooxygenase (COX) inhibitor], or intra-articular [IA] injections), or participant is unable to take NSAIDs because of contraindication or inability to tolerate.
  5. Average daily pain (ADP) numerical rating scale (NRS) score of 4-9 in the index knee at Screening.
  6. Baseline average weekly ADP NRS score of 4-9 in the index knee in the 7 days prior to randomization.
  7. No more than one 24-hr average pain score (0-10 NRS) reported as "10" during the 7 days prior to Day 1.
  8. Body mass index of ≥18.0 to ≤39.0 kg/m2.
  9. Female subjects of childbearing potential and Male subjects must agree to comply with protocol specified contraceptive requirements
  10. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
  11. Completion of at least 11 out of 14 ADP NRS scores for at least 14 days prior to randomisation.
  12. Current non-pharmacologic treatment regimen for knee OA (excluding knee brace) must be stable for at least 2 weeks before Day 1 and remain stable throughout the study. Participant must be willing to abstain from starting a new or changing their non-pharmacologic treatment regimen for the duration of the study.
  13. Willing to stop treatment with oral and topical NSAIDs, and all other systemic pain medications (except allowed rescue medication) from 2 weeks before Day 1 to end of study.
  14. Agrees to use acetaminophen/paracetamol or topical analgesics (topical NSAIDs are prohibited) as rescue therapy if required.

Exclusion Criteria:

  1. History of idiopathic or immune-mediated thrombocytopenia including history of HIT with or without thrombosis.
  2. History of major bleeding disorders including haemophilia.
  3. Currently active or recent history (within preceding 12 months) of a gastric or duodenal ulcer, or suspicion of gastrointestinal tract bleeding.
  4. Recent cerebral bleeding or operation on brain, spine, or eyes within 12 months of Day 1.
  5. Spinal anaesthesia within 14 days of Day 1.
  6. Fibromyalgia, regional pain caused by lumbar or cervical compression with radiculopathy, or other moderate to severe pain disorder that may confound assessments or self-evaluation of the pain associated with osteoarthritis. Participants with a present (current) history of sciatica are not eligible for participation. Participants with a history of sciatica who have been asymptomatic for ≥3 months and who have no evidence of radiculopathy or sciatic neuropathy on thorough neurologic examination are eligible for participation.
  7. History of other disease that may involve the index knee, including inflammatory joint disease such as rheumatoid arthritis (RA), seronegative spondyloarthropathy (e.g., ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease-related arthropathy), crystalline disease (e.g., gout), endocrinopathies, metabolic joint diseases, lupus erythematosus, joint infections, Paget's disease, or tumours.
  8. History of hypersensitivity to PPS, heparin or heparin-like drugs, or drugs of a similar chemical or pharmacological class.
  9. Predisposition to hypersensitivity due to multiple (2 or more) atopic diseases (such as atopic eczema, asthma, and chronic allergic rhinitis and/or rhinoconjunctivitis) or multiple (2 or more) severe allergies.
  10. Allergy or contraindication to tetracosactide (Synacthen®), cosyntropin (Cortrosyn®).
  11. Allergy or contraindication to gadolinium.

  12. Chronic medical conditions including but not limited to those stated below requiring medical regime changes within 60 days before Day 1.

    Concurrent unstable peripheral, cardiac, and cerebral vascular disease, poorly controlled chronic obstructive pulmonary disease and asthma, coagulopathies, uncontrolled neurological conditions, active tuberculosis, active infections, symptomatic cardiac arrhythmias, adrenal insufficiency (primary or central), nephrotic syndrome, cirrhosis (Child-Pugh stage B or C), Gilbert syndrome, uncontrolled diabetes, and uncontrolled hypothyroidism or hyperthyroidism, or mental or emotional disorders that preclude reliable study participation.

  13. History of pituitary irradiation or recent (within 1 year) history of transsphenoidal surgery.
  14. Any cancer within the previous 5 years, except for basal cell carcinomas.
  15. History or current autoimmune polyglandular syndromes.
  16. Presence of any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the participant will comply with the protocol or complete the study per the protocol.
  17. Current treatment with anticoagulants or antiplatelet drugs within 2 weeks before Day 1, excluding aspirin ≤150 mg/day.
  18. Previous treatment with PPS in any form.
  19. Current or recent (within 90 days before Day 1) immunosuppressive or immunomodulatory (with immunosuppressive effects) systemic therapy including but not limited to oral, inhaled, intranasal, intra-articular (IA) and topical corticosteroids (occasional use of topical, inhaled or intranasal corticosteroids is acceptable).
  20. Use of NSAIDs with 2 weeks before Day 1.
  21. Use of opioids within 6 weeks before Day 1.
  22. Use of glucosamine or chondroitin within 6 weeks before Day 1.
  23. Use of bisphosphonates and denosumab within 12 weeks before Day 1.
  24. Use of iloprost within 12 weeks before Day 1.
  25. Use of a knee brace on the index knee within 2 weeks before Day 1.
  26. Systemic steroids administered intravenously, intramuscularly, or orally for OA or other indications within 8 weeks before Day 1.
  27. Intra-articular (IA) injections to the index knee: steroids within 12 weeks before Day 1; hyaluronic acid (HA) or any other IA injections within 24 weeks before Day 1.
  28. Stem cells or platelet-rich plasma within 12 months of Day 1.
  29. Cannabinoids within 30 days before Day 1.
  30. Use of individual vitamins and dietary supplements known to alter haemostasis within 2 weeks before Day 1, including ajoene, birch bark, cayenne, Chinese black tree fungus, cumin, evening primrose oil, feverfew, garlic, ginger, ginkgo biloba, ginseng, grapeseed extract, milk thistle, omega 3 fatty acids, onion extract, St. John's wort, turmeric, vitamins C and E, vitamin K, (multivitamins allowed).
  31. Known exposure to heparin within the last 100 days as determined by history of drug use or history of the following medical conditions or interventions: cardiac bypass surgery or thromboembolic disease.
  32. Treatment with dehydroepiandrosterone sulfates (DHEA-S) within 6 weeks before Day 1.
  33. Chronic use of oral glucocorticoid receptor antagonists or cortisol synthesis inhibitors within 12 weeks before Day 1.
  34. Biotin within 72 hours before Screening.
  35. Megestrol acetate within 6 weeks before Day 1.
  36. Participation in another clinical trial or administration of any IP or experimental product within 24 weeks or 5 half-lives (whichever is longer) before Day 1.
  37. Activated partial thromboplastin time [aPTT]) > 36 seconds, platelets <150,000/μL, or liver enzyme tests (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) ≥ 2 × ULN at Screening.
  38. Total bilirubin ≥1.5 ULN.
  39. Active or chronic hepatitis B virus, hepatitis C virus, or uncontrolled HIV infection (detectable virus or diagnosis of AIDS); participants with HIV infection must be on chronic suppressive antiviral medication.
  40. Evidence of any of the following conditions in any screening imaging: excessive malalignment (≥10 degrees varus or valgus) of the knee, subchondral insufficiency fracture (SIF), osteonecrosis/bone infarct, osteochondritis dissecans, stress or acute fracture, atrophic OA, pathologic fracture, primary or metastatic tumour, infectious arthritis or osteomyelitis, chronic or acute, Charcot's knee joint, synovial chondromatosis, certain posterior root tears of the meniscus, bone contusion, bone marrow oedema syndrome, bone marrow infiltration, gout, severe chondrocalcinosis, other arthropathies (e.g., RA, psoriatic arthritis), systemic metabolic bone disease (e.g., Paget's disease, metastatic calcifications) or other conditions identified by a radiologist or Medical Monitor which may interfere with a participant's assessment of pain.
  41. Any clinically significant abnormalities on clinical chemistry, haematology, urinalysis, physical examination, medical history, or vital signs as judged by the Investigator (at Screening).
  42. Resting, supine blood pressure (BP) ≥160 mmHg in systolic pressure or ≥100 mmHg in diastolic pressure at Screening. If a participant is found to have uncontrolled and/or untreated significant hypertension at Screening and antihypertensive treatment is initiated, assessment for study eligibility should be deferred until BP and antihypertensive medication have been stable for at least 1 month. For participants with previously diagnosed hypertension, antihypertensive medications must be stable for at least 1 month before Screening.
  43. Any macular findings on clinical examination or imaging suggestive of: moderate or advanced dry macular degeneration, geographic atrophy, moderate or advanced myopic degeneration, wet macular degeneration, pattern dystrophy or other pigmentary maculopathy, moderate or severe diabetic or hypertensive retinopathy, recent retinal vascular occlusion, macular hole or advanced epiretinal membrane with associated macular oedema, retinal dystrophy, toxic retinal maculopathy, chronic central serous retinopathy, presence of significant subretinal or intraretinal fluid (OCT finding), presence of vitelliform or vitelliform-like macular changes (OCT and clinical finding), severe maculopathy not otherwise specified.
  44. Morning cortisol <3 μg/dL.
  45. Adrenocorticotropic hormone (ACTH) <10 pg/mL.
  46. US/Canada only: Morning cortisol ≥3 μg/dL and <10 μg/dL and peak cortisol (by ACTH stimulation [250 μg, IM] test) <18 μg/dL at both 30 min and 60 min post stimulation.
  47. Current hyperkalaemia and/or hyponatremia.
  48. Contraindication to MRI.
  49. Largely or wholly incapacitated (e.g., bedridden or confined to a wheelchair, permitting little or no self-care).
  50. Major surgery or anticipated surgery during the study.
  51. Currently hospitalised or any planned hospitalizations during the study.
  52. Plan for total knee reconstruction in affected knee(s) during the study.
  53. Knee surgery or trauma to the index knee within 1 year before Day 1.
  54. A history of drug or alcohol abuse and/or dependence within the 12 months before Screening that, in the opinion of the Investigator, may affect participant ability to comply with study requirements.
  55. An employee of the Sponsor, clinical research organisation(s), or research site personnel directly affiliated with this study or their immediate family members defined as a spouse, parent, sibling, or child, whether biological or legally adopted.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: PPS
Pentosan polysulfate sodium 2mg/kg twice weekly for 6 weeks
Drug: Pentosan Polysulfate Sodium twice weekly
Subcutaneous injection, 2 mg/kg twice weekly for 6 weeks
Placebo Comparator: Placebo
Placebo (Sodium Chloride Injection, 0.9%) twice weekly for 6 weeks
Drug: Placebo
Placebo, subcutaneous injection, twice weekly for 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline at Day 112 in knee pain as assessed by the weekly average of daily pain (ADP) score on the numerical rating scale (NRS) 11-point (0-10) scale.
Time Frame: Baseline, Daily to Day 112

The NRS is an 11-point unidimensional scale for self-report of pain. The participant selects a whole number (0-10) that best reflects the intensity of their pain. The anchors are 0=no pain and 10=extreme pain/worst possible pain. It is often categorised into no pain=0, mild pain=1-3, moderate pain=4-6, severe pain=7-10.

Participants will be asked to consider their average pain over the last 24 hours.
Baseline, Daily to Day 112

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in function as assessed by the average functional subscale score of the WOMAC NRS 3.1 Index
Time Frame: Measured at 20 timepoints from Day 1 to 404.

The WOMAC NRS 3.1 Index is a validated, self-administered, health status questionnaire that assesses pain, stiffness, and function in patients with hip or knee OA (Bellamy et al., 1988).

The WOMAC NRS 3.1 Index consists of 24 questions and produces 3 subscale scores for pain (5 questions), stiffness (2 questions), and function (17 questions) and a total score that summarises overall disability. Each question is scored from 0 to 10 using a standardised 11-point NRS.

Each subscale score and the total score will be averaged to provide subscale and total scores between 0 and 10.

Participants are to consider their last 4 hours when answering the questions.
Measured at 20 timepoints from Day 1 to 404.
Change from baseline in knee pain as assessed by the average pain subscale score of the WOMAC NRS 3.1 Index
Time Frame: Measured at 20 timepoints from Day 1 to 404.

The WOMAC NRS 3.1 Index is a validated, self-administered, health status questionnaire that assesses pain, stiffness, and function in patients with hip or knee OA (Bellamy et al., 1988).

The WOMAC NRS 3.1 Index consists of 24 questions and produces 3 subscale scores for pain (5 questions), stiffness (2 questions), and function (17 questions) and a total score that summarises overall disability. Each question is scored from 0 to 10 using a standardised 11-point NRS.

Each subscale score and the total score will be averaged to provide subscale and total scores between 0 and 10.

Participants are to consider their last 4 hours when answering the questions.
Measured at 20 timepoints from Day 1 to 404.
Change from baseline in knee pain as assessed by the weekly average of daily pain (ADP) score on the numerical rating scale (NRS) 11-point (0-10) scale.
Time Frame: Measured at 21 timepoints from Screening to Day 404.

The NRS is an 11-point unidimensional scale for self-report of pain. The participant selects a whole number (0-10) that best reflects the intensity of their pain. The anchors are 0=no pain and 10=extreme pain/worst possible pain. It is often categorised into no pain=0, mild pain=1-3, moderate pain=4-6, severe pain=7-10.

Participants will be asked to consider their average pain over the last 24 hours.
Measured at 21 timepoints from Screening to Day 404.
Change from baseline in Patient Global Impression of Change (PGIC)
Time Frame: Measured at 10 timepoints from Days 39 to 404.
The PGIC is a self-administered question that rates participants' overall improvement in chronic pain since beginning treatment from 1 "no change (or condition has worsened)" to 7 "a great deal better" in response to the question "Since beginning treatment, how would you describe the change (if any) in activity, limitation, symptoms, emotions, and overall QoL related to your arthritis".
Measured at 10 timepoints from Days 39 to 404.
Change from baseline in knee stiffness as assessed by the average stiffness subscale score of the WOMAC NRS 3.1 Index
Time Frame: Measured at 20 timepoints from Day 1 to 404.

The WOMAC NRS 3.1 Index is a validated, self-administered, health status questionnaire that assesses pain, stiffness, and function in patients with hip or knee OA (Bellamy et al., 1988).

The WOMAC NRS 3.1 Index consists of 24 questions and produces 3 subscale scores for pain (5 questions), stiffness (2 questions), and function (17 questions) and a total score that summarises overall disability. Each question is scored from 0 to 10 using a standardised 11-point NRS.

Each subscale score and the total score will be averaged to provide subscale and total scores between 0 and 10.

Participants are to consider their last 4 hours when answering the questions.
Measured at 20 timepoints from Day 1 to 404.
Change from baseline overall as assessed by the overall score of the WOMAC NRS 3.1 Index
Time Frame: Measured at 20 timepoints from Day 1 to 404.

The WOMAC NRS 3.1 Index is a validated, self-administered, health status questionnaire that assesses pain, stiffness, and function in patients with hip or knee OA (Bellamy et al., 1988).

The WOMAC NRS 3.1 Index consists of 24 questions and produces 3 subscale scores for pain (5 questions), stiffness (2 questions), and function (17 questions) and a total score that summarises overall disability. Each question is scored from 0 to 10 using a standardised 11-point NRS.

Each subscale score and the total score will be averaged to provide subscale and total scores between 0 and 10.

Participants are to consider their last 4 hours when answering the questions.
Measured at 20 timepoints from Day 1 to 404.
Proportion of participants with ≥30% and ≥50% pain reduction from baseline as assessed by the average pain subscale score of the WOMAC NRS 3.1 Index.
Time Frame: Measured at 20 timepoints from Day 1 to 404.

The WOMAC NRS 3.1 Index is a validated, self-administered, health status questionnaire that assesses pain, stiffness, and function in patients with hip or knee OA (Bellamy et al., 1988).

The WOMAC NRS 3.1 Index consists of 24 questions and produces 3 subscale scores for pain (5 questions), stiffness (2 questions), and function (17 questions) and a total score that summarises overall disability. Each question is scored from 0 to 10 using a standardised 11-point NRS.

Each subscale score and the total score will be averaged to provide subscale and total scores between 0 and 10.

Participants are to consider their last 4 hours when answering the questions.
Measured at 20 timepoints from Day 1 to 404.
Proportion of participants with ≥30% and ≥50% improvement in function from baseline as assessed by the average pain subscale score of the WOMAC NRS 3.1 Index.
Time Frame: Measured at 20 timepoints from Day 1 to 404.

The WOMAC NRS 3.1 Index is a validated, self-administered, health status questionnaire that assesses pain, stiffness, and function in patients with hip or knee OA (Bellamy et al., 1988).

The WOMAC NRS 3.1 Index consists of 24 questions and produces 3 subscale scores for pain (5 questions), stiffness (2 questions), and function (17 questions) and a total score that summarises overall disability. Each question is scored from 0 to 10 using a standardised 11-point NRS.

Each subscale score and the total score will be averaged to provide subscale and total scores between 0 and 10.

Participants are to consider their last 4 hours when answering the questions.
Measured at 20 timepoints from Day 1 to 404.
Number of days of rescue medication used
Time Frame: Recorded from Day 1 to 404
In case of inadequate pain relief, either acetaminophen/paracetamol up to 3000 mg per day or topical analgesics, up to 4 days in a week may be taken as rescue medication between day 1 and Day 404. Participants will record all use of rescue and other pain medications/therapies in their electronic diary.
Recorded from Day 1 to 404
Change from baseline in QoL as assessed by EQ-5D-5L.
Time Frame: Measured at 13 timepoints from Days 1 to 404
The EQ-5D-5L questionnaire is a self-assessed, health related, QoL questionnaire consisting of the EQ-5D descriptive system and the EQ VAS. The descriptive system comprises of five dimensions, where each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The patient is asked to indicate their health state by ticking the box next to the most appropriate statement in each of the five dimensions.
Measured at 13 timepoints from Days 1 to 404
Change from baseline in cartilage volume and thickness on Magnetic Resonance Imaging (MRI).
Time Frame: Measured at Days 1, 168 and 404.
Gadolinium MRI images will be taken to measure changes in cartilage volume and thickness.
Measured at Days 1, 168 and 404.
Change from baseline in joint synovitis/effusion volume on Magnetic Resonance Imaging (MRI).
Time Frame: Measured at Days 1, 168 and 404.
Gadolinium MRI images will be taken to measure changes in joint synovitis/effusion volume,.
Measured at Days 1, 168 and 404.
Change from baseline in subchondral BML area and volume on Magnetic Resonance Imaging (MRI).
Time Frame: Measured at Days 1, 168 and 404.
Gadolinium MRI images will be taken to measure changes in subchondral BML area and volume,.
Measured at Days 1, 168 and 404.
Change from baseline in bone shape/osteophytes on Magnetic Resonance Imaging (MRI).
Time Frame: Measured at Days 1, 168 and 404.
Gadolinium MRI images will be taken to measure changes in bone shape/osteophytes.
Measured at Days 1, 168 and 404.
Change from baseline in joint space width on X-ray.
Time Frame: Measured at Days 1 and 404.
X-ray for comparison of joint space width
Measured at Days 1 and 404.
OMERACT-OARSI Responder Index response rate
Time Frame: Measured at 10 timepoints from Days 39 to 404.

OMERACT-OARSI-Outcome Measures in Rheumatology-Osteoarthritis Research Society International.

Participants are considered as an OMERACT-OARSI responder: if the change (improvement) from baseline to day of interest was greater than or equal to >= 50 percent and >= 2 units in either WOMAC pain sub-scale or physical function sub-scale score; if change (improvement) from baseline to week of interest was >=20 percent and >=1 unit in at least 2 of the following: 1) WOMAC pain sub-scale score, 2) WOMAC physical function sub-scale score, 3) Patient Global Impression of Change (PGIC).
Measured at 10 timepoints from Days 39 to 404.
Change from baseline in Work Productivity and Activity Impairment (WPAI) questionnaire score
Time Frame: Measured at 10 timepoints from Day 39 to 404.
The WPAI questionnaire (WPAI:OA-knee) is a validated self-administered questionnaire that assesses work impairment due to OA . The questionnaire gathers information on employment status, hours worked, hours missed due to OA, and hours missed for any other reasons.
Measured at 10 timepoints from Day 39 to 404.
Incidence of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs)
Time Frame: From enrollment to Day 404

An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.

An SAE is any untoward medical occurrence that at any dose results in one or more of the following outcomes: death; life-threatening; requires in-patient hospitalization or prolongation of an existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; is an important medical event.

Treatment-emergent means events occurring between the first dose of study drug and up to Day 404 that were absent before treatment or that worsened relative to pre-treatment state.
From enrollment to Day 404
Incidence of treatment-emergent clinical abnormalities
Time Frame: From enrollment to Day 404
Treatment-emergent clinical laboratory abnormalities are abnormalities in laboratory results between the first dose of study drug and up to Day 404 that were absent before treatment or that worsened relative to pre-treatment state
From enrollment to Day 404

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exploratory: Characterize the AUC profile of single and multiple doses based on sparse blood sampling. (pharmacokinetic subset only)
Time Frame: Days 1, 15 and 39 - pre-dose and 2, 4, and 6 hours. Pre-dose on day 4, 8, 11, 18, 22, 25, 29, 32, 36 and 39

Blood samples for assay of plasma PPS concentration will be obtained from a subset of patients before dosing and 2, 4, and 6 hours after dosing on study Days 1, 15 and 39. On other days, a pre-dose sample will be collected. Samples will be assayed using a sensitive, validated bioanalytical method.

Plasma concentrations of PPS will be tabulated by time and participant and inspected for relationship to dose during titration and stable treatment phases.
Days 1, 15 and 39 - pre-dose and 2, 4, and 6 hours. Pre-dose on day 4, 8, 11, 18, 22, 25, 29, 32, 36 and 39
Exporatory: Number of participants with an Anti-Drug-Antibody (ADA) response after treatment and correlation with clinical events.
Time Frame: Baseline, Days 11, 25, 39, 56 and 84.
Human serum ADA samples will be analyzed for the presence or absence of anti-drug-antibodies by using a semi-quantitative enzyme linked immunosorbent assay (ELISA).
Baseline, Days 11, 25, 39, 56 and 84.
Exploratory: Change from baseline in serum biomarkers, including but not limited to, COMP, aggrecan ARGS, CRTAC-1, PRO-C2 PIIBNP, NTx-Ⅰ, and HA.
Time Frame: Measured at 11 timepoints from Day 4 to 168.
ARGS-(aggrecan) alanine-arginine-glycine-serine; COMP-cartilage oligomeric matrix protein; CRTAC-1-cartilage acidic protein-1; HA-hyaluronic acid; NTx-1-N-terminal telopeptide of type I collagen; PIIBNP-N-terminal propeptide of type II collagen; PRO-C2-type II collagen C-terminal propeptide.
Measured at 11 timepoints from Day 4 to 168.
Exploratory: Change from baseline of cartilage volume and thickness and whether these correlate with clinical pain outcomes.
Time Frame: Screening, Day 168 and 404
The correlation co-efficient of changes in cartilage volume and thickness as measured on MRI and pain clinical outcomes.
Screening, Day 168 and 404
Exploratory: Change from baseline of subchondral BMLs, and whether these correlate with clinical pain outcomes.
Time Frame: Screening , Day 168 and 404
The correlation co-efficient of changes in subchondral BMLs as measured on MRI and pain clinical outcomes.
Screening , Day 168 and 404
Exploratory: Change from baseline of bone shape and whether these correlate with clinical pain outcomes.
Time Frame: Screening , Day 168 and 404
• The correlation co-efficient of changes in bone shape changes as measured on MRI and pain clinical outcomes
Screening , Day 168 and 404
Exploratory: Change from baseline of joint space width and whether these correlate with clinical pain outcomes.
Time Frame: Screening and 404
The correlation co-efficient between changes in joint space width as measured on X-Ray and clinical pain outcomes.
Screening and 404

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Paradigm Biopharmaceuticals Ltd.

Investigators

  • Study Director: Chief Medical Officer, Medical, Paradigm Biopharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 29, 2025

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

July 1, 2027

Study Registration Dates

First Submitted

March 11, 2025

First Submitted That Met QC Criteria

March 31, 2025

First Posted (Actual)

April 8, 2025

Study Record Updates

Last Update Posted (Actual)

May 8, 2026

Last Update Submitted That Met QC Criteria

May 6, 2026

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PARA_OA_012

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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