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

NCT06917404 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: PARA_OA_012
• Study Type: interventional
• Target: 466
• Locations: 3 countries
• Sites: 52

Brief Summary

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.

Conditions

Osteoarthritis, Knee

Keywords

osteoarthritis; knee

Outcome Measures

Primary Outcomes (1)

• 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.

  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 Outcomes (19)

• Change from baseline in function as assessed by the average functional subscale score of the WOMAC NRS 3.1 Index

  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

  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.

  Measured at 21 timepoints from Screening to Day 404.

• Change from baseline in Patient Global Impression of Change (PGIC)

  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

  Measured at 20 timepoints from Day 1 to 404.

Other Outcomes (7)

• Exploratory: Characterize the AUC profile of single and multiple doses based on sparse blood sampling. (pharmacokinetic subset only)

  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.

  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.

  Measured at 11 timepoints from Day 4 to 168.

Study Arms (2)

PPS

ACTIVE COMPARATOR

Pentosan polysulfate sodium 2mg/kg twice weekly for 6 weeks

Drug: Pentosan Polysulfate Sodium twice weekly

Placebo

PLACEBO COMPARATOR

Placebo (Sodium Chloride Injection, 0.9%) twice weekly for 6 weeks

Drug: Placebo

Interventions

Pentosan Polysulfate Sodium twice weekly DRUG

Subcutaneous injection, 2 mg/kg twice weekly for 6 weeks

PPS

Placebo DRUG

Placebo, subcutaneous injection, twice weekly for 6 weeks

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be ≥18 years of age inclusive, at the time of signing the informed consent.
• Clinical diagnosis of OA in the index knee by American College of Rheumatology 1986 criteria.
• 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.
• 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.
• Average daily pain (ADP) numerical rating scale (NRS) score of 4-9 in the index knee at Screening.
• Baseline average weekly ADP NRS score of 4-9 in the index knee in the 7 days prior to randomization.
• No more than one 24-hr average pain score (0-10 NRS) reported as "10" during the 7 days prior to Day 1.
• Body mass index of ≥18.0 to ≤39.0 kg/m2.
• Female subjects of childbearing potential and Male subjects must agree to comply with protocol specified contraceptive requirements
• 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.
• Completion of at least 11 out of 14 ADP NRS scores for at least 14 days prior to randomisation.
• 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.
• 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.
• Agrees to use acetaminophen/paracetamol or topical analgesics (topical NSAIDs are prohibited) as rescue therapy if required.

You may not qualify if:

• History of idiopathic or immune-mediated thrombocytopenia including history of HIT with or without thrombosis.
• History of major bleeding disorders including haemophilia.
• Currently active or recent history (within preceding 12 months) of a gastric or duodenal ulcer, or suspicion of gastrointestinal tract bleeding.
• Recent cerebral bleeding or operation on brain, spine, or eyes within 12 months of Day 1.
• Spinal anaesthesia within 14 days of Day 1.
• 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.
• 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.
• History of hypersensitivity to PPS, heparin or heparin-like drugs, or drugs of a similar chemical or pharmacological class.
• 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.
• Allergy or contraindication to tetracosactide (Synacthen®), cosyntropin (Cortrosyn®).
• Allergy or contraindication to gadolinium.
• 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.
• History of pituitary irradiation or recent (within 1 year) history of transsphenoidal surgery.
• Any cancer within the previous 5 years, except for basal cell carcinomas.

Sponsors & Collaborators

• Paradigm Biopharmaceuticals Ltd.: lead

Study Sites (52)

Onyx Clinical Research-Peoria

Peoria, Arizona, 85381, United States

RECRUITING

Del Sol Research Management, LLC

Tucson, Arizona, 85715, United States

RECRUITING

Orange County Research Institute

Anaheim, California, 92801, United States

RECRUITING

Core Healthcare Group

Cerritos, California, 90703, United States

RECRUITING

Triwest Research Center

Chula Vista, California, 91910, United States

RECRUITING

Seaside Medical Group

Oceanside, California, 92058, United States

RECRUITING

Paragon RX Clinical

Santa Ana, California, 92703, United States

RECRUITING

Encompass Clinical Research

Spring Valley, California, 91978, United States

RECRUITING

Focus Clinical Research

West Hills, California, 91307, United States

RECRUITING

Clinical Research of West Florida - Clearwater

Clearwater, Florida, 33765, United States

RECRUITING

GNP Research

Cooper City, Florida, 33024, United States

RECRUITING

Arrow Clinical Trials

Daytona Beach, Florida, 32117, United States

RECRUITING

AGA Clinical Trials

Hialeah, Florida, 33012, United States

RECRUITING

Evolution Clinical Trials

Miami, Florida, 33122, United States

RECRUITING

Well Pharma Medical Research

Miami, Florida, 33173, United States

RECRUITING

K2 Medical Research

Orlando, Florida, 32806, United States

RECRUITING

Progressive Medical Research

Port Orange, Florida, 32127, United States

RECRUITING

Phoenix Clinical Research

Tamarac, Florida, 33321, United States

RECRUITING

Conquest Research

Winter Park, Florida, 32789, United States

RECRUITING

Chicago Clinical Research, Inc

Chicago, Illinois, 60607, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

RECRUITING

Profound Research

Farmington Hills, Michigan, 48334, United States

RECRUITING

Insight Research Institute

Flint, Michigan, 48507, United States

RECRUITING

Rochester Medical Group

Rochester Hills, Michigan, 48307, United States

RECRUITING

Onyx Clinical Research - Rochester Hills

Troy, Michigan, 48085, United States

RECRUITING

Physician Research Collaboration

Lincoln, Nebraska, 68516, United States

RECRUITING

Alpine Healthcare Family Practice

Las Vegas, Nevada, 89109, United States

RECRUITING

Drug Trials America

Hartsdale, New York, 10530, United States

RECRUITING

IMA Clinical Research Manhattan

New York, New York, 10036, United States

RECRUITING

Groth Pain and Spine Management

Smithtown, New York, 11787, United States

RECRUITING

FutureSearch Trials of Neurology

Austin, Texas, 78731, United States

RECRUITING

FutureSearch Trials of Dallas

Dallas, Texas, 75251, United States

RECRUITING

Vilo Research Group

Houston, Texas, 77017, United States

RECRUITING

DM Clinical Research

Houston, Texas, 77065, United States

RECRUITING

Clinical Trial Network

Houston, Texas, 77074, United States

RECRUITING

Epic Clinical Research

Lewisville, Texas, 75057, United States

RECRUITING

Quality Research Inc.

San Antonio, Texas, 78209, United States

RECRUITING

Rio Clinical Trials

Ogden, Utah, 84404, United States

RECRUITING

Canopy Clinical Research-Northern Beaches

Brookvale, New South Wales, 2100, Australia

RECRUITING

Novatrials

Charlestown, New South Wales, 2290, Australia

RECRUITING

Canopy Clinical Research - Sutherland Shire

Miranda, New South Wales, 2228, Australia

RECRUITING

Canopy Clinical Research-Wollongong

Wollongong, New South Wales, 2500, Australia

RECRUITING

Mater Health Brisbane

South Brisbane, Queensland, 4101, Australia

RECRUITING

Griffith University

Southport, Queensland, 4222, Australia

RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

RECRUITING

Sportsmed

Stepney, South Australia, 5069, Australia

RECRUITING

Canopy Clinical Research-Altona North

Altona N., Victoria, 3025, Australia

RECRUITING

Sportsmed Biologic LTD

Box Hill, Victoria, 3128, Australia

RECRUITING

Clinitrials

Perth, Western Australia, 6000, Australia

RECRUITING

RK Will Pty Ltd

Victoria Park, Western Australia, 6100, Australia

RECRUITING

Hong Kong Centre for Clinical Research

Hong Kong, Hong Kong

RECRUITING

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Chief Medical Officer, Medical

  Paradigm Biopharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Donna Skerrett

CONTACT

+1 (312) 771 9615; info@paradigmbiopharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2025
• First Posted: April 8, 2025
• Study Start: May 29, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: April 30, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1); US (39); AU (12)