Osteoarthritis, KneePhase 3NCT06917404
A Study to Investigate the Treatment Effect of Subcutaneous Injections of Pentosan Polysulfate Sodium Compared With Placebo in Adult Participants With Knee Osteoarthritis Pain.
A Phase 3 study testing Pentosan Polysulfate Sodium twice weekly in people with Osteoarthritis, Knee, run by Paradigm Biopharmaceuticals Ltd. at 57 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Osteoarthritis, Knee
- What is being tested?
- Pentosan Polysulfate Sodium twice weekly
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 466 participants
- Where
- 57 sitesin 4 countries
- Study dates
- 29 May 2025to Jul 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 14Show fewer
- 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.
Who cannot join
- 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.
Show all 56Show fewer
- 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.
- History or current autoimmune polyglandular syndromes.
- 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.
- Current treatment with anticoagulants or antiplatelet drugs within 2 weeks before Day 1, excluding aspirin ≤150 mg/day.
- Previous treatment with PPS in any form.
- 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).
- Use of NSAIDs with 2 weeks before Day 1.
- Use of opioids within 6 weeks before Day 1.
- Use of glucosamine or chondroitin within 6 weeks before Day 1.
- Use of bisphosphonates and denosumab within 12 weeks before Day 1.
- Use of iloprost within 12 weeks before Day 1.
- Use of a knee brace on the index knee within 2 weeks before Day 1.
- Systemic steroids administered intravenously, intramuscularly, or orally for OA or other indications within 8 weeks before Day 1.
- 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.
- Stem cells or platelet-rich plasma within 12 months of Day 1.
- Cannabinoids within 30 days before Day 1.
- 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).
- 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.
- Treatment with dehydroepiandrosterone sulfates (DHEA-S) within 6 weeks before Day 1.
- Chronic use of oral glucocorticoid receptor antagonists or cortisol synthesis inhibitors within 12 weeks before Day 1.
- Biotin within 72 hours before Screening.
- Megestrol acetate within 6 weeks before Day 1.
- 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.
- 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.
- Total bilirubin ≥1.5 ULN.
- 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.
- 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.
- Any clinically significant abnormalities on clinical chemistry, haematology, urinalysis, physical examination, medical history, or vital signs as judged by the Investigator (at Screening).
- 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.
- 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.
- Morning cortisol <3 μg/dL.
- Adrenocorticotropic hormone (ACTH) <10 pg/mL.
- 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.
- Current hyperkalaemia and/or hyponatremia.
- Contraindication to MRI.
- Largely or wholly incapacitated (e.g., bedridden or confined to a wheelchair, permitting little or no self-care).
- Major surgery or anticipated surgery during the study.
- Currently hospitalised or any planned hospitalizations during the study.
- Plan for total knee reconstruction in affected knee(s) during the study.
- Knee surgery or trauma to the index knee within 1 year before Day 1.
- 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.
- 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.
Trial locations and contacts
57 sites in 4 countries.
57 sites in 4 countries
United States41 sites
Orange County Research Institute
Anaheim, California, 92801
FutureSearch Trials of Neurology
Austin, Texas, 78731
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
Core Healthcare Group
Cerritos, California, 90703
Chicago Clinical Research, Inc
Chicago, Illinois, 60607
Northwestern University
Chicago, Illinois, 60611
Triwest Research Center
Chula Vista, California, 91910
Clinical Research of West Florida - Clearwater
Clearwater, Florida, 33765
GNP Research
Cooper City, Florida, 33024
FutureSearch Trials of Dallas
Dallas, Texas, 75251
Arrow Clinical Trials
Daytona Beach, Florida, 32117
El Paso Clinical Trials
El Paso, Texas, 79935
Profound Research
Farmington Hills, Michigan, 48334
Insight Research Institute
Flint, Michigan, 48507
Drug Trials America
Hartsdale, New York, 10530
AGA Clinical Trials
Hialeah, Florida, 33012
Vilo Research Group
Houston, Texas, 77017
DM Clinical Research
Houston, Texas, 77065
Clinical Trial Network
Houston, Texas, 77074
Alpine Healthcare Family Practice
Las Vegas, Nevada, 89109
Epic Clinical Research
Lewisville, Texas, 75057
Physician Research Collaboration
Lincoln, Nebraska, 68516
Evolution Clinical Trials
Miami, Florida, 33122
Well Pharma Medical Research
Miami, Florida, 33173
Groth Pain & Spine - Long Island, NY
Mineola, New York, 11501
IMA Clinical Research Manhattan
New York, New York, 10036
Seaside Medical Group
Oceanside, California, 92058
Rio Clinical Trials
Ogden, Utah, 84404
K2 Medical Research
Orlando, Florida, 32806
Onyx Clinical Research-Peoria
Peoria, Arizona, 85381
Progressive Medical Research
Port Orange, Florida, 32127
Rochester Medical Group
Rochester Hills, Michigan, 48307
Quality Research Inc.
San Antonio, Texas, 78209
Paragon RX Clinical
Santa Ana, California, 92703
Groth Pain and Spine Management
Smithtown, New York, 11787
Encompass Clinical Research
Spring Valley, California, 91978
Phoenix Clinical Research
Tamarac, Florida, 33321
Onyx Clinical Research - Rochester Hills
Troy, Michigan, 48085
Del Sol Research Management, LLC
Tucson, Arizona, 85715
Focus Clinical Research
West Hills, California, 91307
Conquest Research
Winter Park, Florida, 32789
Australia12 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Canopy Clinical Research-Altona North
Altona N., Victoria, 3025
Sportsmed Biologic LTD
Box Hill, Victoria, 3128
Canopy Clinical Research-Northern Beaches
Brookvale, New South Wales, 2100
Novatrials
Charlestown, New South Wales, 2290
Canopy Clinical Research - Sutherland Shire
Miranda, New South Wales, 2228
Clinitrials
Perth, Western Australia, 6005
Mater Health Brisbane
South Brisbane, Queensland, 4101
Griffith University
Southport, Queensland, 4222
Sportsmed
Stepney, South Australia, 5069
RK Will Pty Ltd
Victoria Park, Western Australia, 6100
Canopy Clinical Research-Wollongong
Wollongong, New South Wales, 2500
Moldova3 sites
PMSI "Timofei Mosneaga" Republican Clinical Hospital
Chisinau, MD2025
PMSI Institute of Cardiology
Chisinau, MD2025
PMSI "Sfanta Treime" Municipal Clinical Hospital
Chisinau, MD2068
About this study
Official title: 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.
Read the 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
- Conditions
- Osteoarthritis, Knee
- Being tested
- Pentosan Polysulfate Sodium twice weekly, Placebo
- Keywords
- osteoarthritis, knee
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pentosan Polysulfate Sodium twice weeklyDrug
Subcutaneous injection, 2 mg/kg twice weekly for 6 weeks
PlaceboDrug
Placebo, subcutaneous injection, twice weekly for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| PPS | Active comparator | Pentosan polysulfate sodium 2mg/kg twice weekly for 6 weeks Receives: Drug: Pentosan Polysulfate Sodium twice weekly |
| Placebo | Placebo comparator | Placebo (Sodium Chloride Injection, 0.9%) twice weekly for 6 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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: 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
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: 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.
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: Measured at 21 timepoints from Screening to Day 404.
Change from baseline in Patient Global Impression of Change (PGIC)
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: 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
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: 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
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: 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.
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: 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.
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: Measured at 20 timepoints from Day 1 to 404.
Number of days of rescue medication used
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.
Measured: Recorded from Day 1 to 404
Change from baseline in QoL as assessed by EQ-5D-5L.
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: Measured at 13 timepoints from Days 1 to 404
Change from baseline in cartilage volume and thickness on Magnetic Resonance Imaging (MRI).
Gadolinium MRI images will be taken to measure changes in cartilage volume and thickness.
Measured: Measured at Days 1, 168 and 404.
Change from baseline in joint synovitis/effusion volume on Magnetic Resonance Imaging (MRI).
Gadolinium MRI images will be taken to measure changes in joint synovitis/effusion volume,.
Measured: Measured at Days 1, 168 and 404.
Change from baseline in subchondral BML area and volume on Magnetic Resonance Imaging (MRI).
Gadolinium MRI images will be taken to measure changes in subchondral BML area and volume,.
Measured: Measured at Days 1, 168 and 404.
Change from baseline in bone shape/osteophytes on Magnetic Resonance Imaging (MRI).
Gadolinium MRI images will be taken to measure changes in bone shape/osteophytes.
Measured: Measured at Days 1, 168 and 404.
Change from baseline in joint space width on X-ray.
X-ray for comparison of joint space width
Measured: Measured at Days 1 and 404.
OMERACT-OARSI Responder Index response rate
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: Measured at 10 timepoints from Days 39 to 404.
Change from baseline in Work Productivity and Activity Impairment (WPAI) questionnaire score
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: Measured at 10 timepoints from Day 39 to 404.
Incidence of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs)
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.
Measured: From enrollment to Day 404
Incidence of treatment-emergent clinical abnormalities
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
Measured: From enrollment to Day 404
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2025
- Study start29 May 2025
- Primary completionJul 2027 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 466 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Paradigm Biopharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chief Medical Officer, Medical, Study director, Paradigm Biopharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06917404
- Sponsor's protocol ID
- PARA_OA_012
- Status last verified
- Aug 2026
- First submitted
- 11 Mar 2025
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06917404
- Acronym / sponsor ID
- PARA_OA_012
- Conditions
- Osteoarthritis, Knee
- Keywords
- osteoarthritis, knee
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 466 participants (estimated)
- Lead sponsor
- Paradigm Biopharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- 29 May 2025 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 8 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PPS | Active comparator | Drug: Pentosan Polysulfate Sodium twice weeklyPentosan polysulfate sodium 2mg/kg twice weekly for 6 weeks |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo (Sodium Chloride Injection, 0.9%) twice weekly for 6 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (56 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pentosan Polysulfate Sodium twice weeklySubcutaneous injection, 2 mg/kg twice weekly for 6 weeks | Drug | PPS |
| PlaceboPlacebo, subcutaneous injection, twice weekly for 6 weeks | Drug | Placebo |
Primary outcome
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.
19 secondary outcomes
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.
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.
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.
Change from baseline in Patient Global Impression of Change (PGIC)
Time frame: 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.
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.
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.
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.
Number of days of rescue medication used
Time frame: 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
Change from baseline in cartilage volume and thickness on Magnetic Resonance Imaging (MRI).
Time frame: 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.
Change from baseline in subchondral BML area and volume on Magnetic Resonance Imaging (MRI).
Time frame: 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.
Change from baseline in joint space width on X-ray.
Time frame: Measured at Days 1 and 404.
OMERACT-OARSI Responder Index response rate
Time frame: 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.
Incidence of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs)
Time frame: From enrollment to Day 404
Incidence of treatment-emergent clinical abnormalities
Time frame: From enrollment to Day 404
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2026.
- Individual participant dataSharing planned: No
Related trials for Osteoarthritis, Knee
Not yet recruiting
Holistic Healing for Knee Osteoarthritis
Knee Osteoarthritis (Knee OA)
Recruiting
Effect of Anti-inflammatory Diet in Osteoarthritis
Osteoarthritis, Knee
Active, not recruitingPhase 2/3
Single vs Triple Hyaluronic Acid in Knee Osteoarthritis
Osteoarthritis, Knee
Not yet recruiting
The Feasibility of a Virtual/Home-based OA Treatment Program in Older Adults With OA and Multimorbidity
Osteoarthritis of the Knee
RecruitingObservational study
Exploring Factors Linked to Worsening Over Time in People With Early-stage Knee Osteoarthritis and Those With Prior Proven Acute Knee Injury.
Knee Osteoarthritis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chief Medical Officer, Medical study director
Paradigm Biopharmaceuticals
57 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pentosan Polysulfate Sodium twice weekly in people with Osteoarthritis, Knee, run by Paradigm Biopharmaceuticals Ltd. at 57 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 56 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 57 sites in United States, Australia, Moldova, Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.