Evaluation of Pentosan Polysulfate Sodium in a drug combination for adults with knee osteoarthritis pain
- Trial ID
- 2022-500228-31-01
- Protocol
- PARA_OA_002
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the treatment effect of **Pentosan Polysulfate Sodium (PPS)** on knee pain and function in participants with knee osteoarthritis (OA) pain. This is clinically relevant as knee OA is a prevalent condition that significantly impacts mobility and quality of life, and effective management of pain and function is crucial for improving patient outcomes.
Secondary objectives include evaluating the treatment effect of PPS on knee pain and function in participants with knee OA pain, with function being included as a co-primary endpoint for the European Medicines Agency (EMA) and Medicines and Health Product Regulatory Agency (MHRA), but still tested in hierarchical order. This further assessment is important to understand the comprehensive impact of PPS on both pain relief and functional improvement in knee OA patients.
Participants
The clinical trial involves a total of **858 participants** who are experiencing **knee osteoarthritis pain**. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on a clinical diagnosis of osteoarthritis in the index knee, confirmed by radiographic evidence and classified as K-L Grade 2, 3, or 4. The trial specifically targets individuals whose osteoarthritis pain in the index knee has been unresponsive to conservative therapy for at least six months prior to screening. Participants are required to have an average WOMAC® NRS 3.1 Index pain subscale score of 4 to 10 in the index knee at screening, with a minimum pain score of 4 on either pain on walking on a flat surface or pain on climbing stairs. Additionally, the average WOMAC® NRS 3.1 Index function subscale score must also be between 4 and 10. The study includes individuals with a body mass index ranging from 18.0 to 39.0 kg/m². Participants must be willing to discontinue the use of oral and topical NSAIDs, as well as other systemic pain medications, except for acetaminophen/paracetamol as per the rescue protocol, from two weeks before the start of the study until its conclusion. The trial does not exclude vulnerable populations, and lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy of **pentosan polysulfate sodium** in participants with knee osteoarthritis pain. The trial is structured in two stages and will be conducted across multiple centers. The primary objective is to assess the treatment effect on knee pain and function, with the primary endpoints being changes from baseline in knee pain and function as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC®) Numeric Rating Scale (NRS) 3.1 Index at Day 56. Secondary endpoints include further assessments at Day 84.
The trial is expected to last until October 2024, with participant recruitment having commenced in March 2023. Participants will be involved in the study for a maximum of 8 weeks, with the treatment period lasting up to 6 weeks. The study includes several key visits: an initial screening visit to confirm eligibility based on criteria such as age, clinical and radiographic diagnosis of knee osteoarthritis, and pain scores; follow-up visits to monitor progress and collect data on primary and secondary endpoints; and an end-of-study visit to conclude participation and gather final data.
Participants are required to discontinue the use of oral and topical NSAIDs and other systemic pain medications, except for acetaminophen/paracetamol as per the rescue protocol, from two weeks before the first day of treatment until the end of the study. Conditions that may lead to early termination from the study include non-compliance with the study protocol, adverse events, or withdrawal of consent. The trial is conducted under strict adherence to ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.
Treatment
The clinical trial involves the administration of **Pentosan polysulfate sodium**, a semi-synthetic sulfated polyxylose, as the primary experimental medication. This compound is provided in a **solution for injection** form and is administered subcutaneously. The dosing regimen is based on body weight, with a maximum daily dose of 2.0 mg/kg and a total maximum dose of 18 mg/kg over a treatment period of 6 weeks. Participant compliance with the dosing schedule is monitored throughout the trial.
**Synacthen** (tetracosactide) is included as an auxiliary treatment in the study. It is available as a **solution for injection** and is administered via injection. The maximum daily dose is 0.25 mg, with a total maximum dose of 8 mg over an 8-week period. This treatment is not the primary focus of the study but is used to support the trial's objectives.
**Sodium Chloride 0.9% w/v for injection** is utilized as a placebo in the trial. It serves as a control to evaluate the efficacy of the experimental treatment. The pharmaceutical form and administration details are not specified, as it is primarily used to maintain blinding in the study.
Several formulations of **Paracetamol** are used as standard-of-care therapy for managing pain in participants. These include Paracetamol Aurovitas, Paracetamol Teva, PARALEN, Panadol Novum, Paracetamol Biofarm, and Paracetamol Accord, all provided in **tablet** form. The oral administration of paracetamol is standardized with a maximum daily dose of 3 grams and a total maximum dose of 96 grams over an 8-week period. Compliance with the dosing regimen is monitored to ensure consistent pain management across participants.
Efficacy
The efficacy of the clinical trial will be assessed using specific endpoints to evaluate the treatment effect of **Pentosan Polysulfate Sodium** (PPS) on knee pain and function in participants with knee osteoarthritis (OA) pain. The primary endpoints include the change from baseline at Day 56 in knee pain, as assessed by the average pain subscale score of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC®) Numeric Rating Scale (NRS) 3.1 Index, and the change from baseline at Day 56 in function, as assessed by the average functional subscale score of the WOMAC® NRS 3.1 Index. These endpoints will be measured and analyzed in a hierarchical order.
Secondary endpoints include the change from baseline at Day 56 in function, which will be a key secondary endpoint in the United States, and the change from baseline at Day 84 in both knee pain and function, as assessed by the WOMAC® NRS 3.1 Index. The efficacy parameters will be collected at specified timepoints, including Day 56 and Day 84, to evaluate the progression and impact of the treatment over time. The WOMAC® NRS 3.1 Index, a validated scale, will be utilized as the primary tool for efficacy assessments, ensuring a standardized approach to measuring symptom improvement in knee OA pain and function.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male and Female Participants 18 years of age or older
- 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.
- Osteoarthritis pain in the index knee unresponsive to conservative therapy for ≥6 months preceding Screening
- Average WOMAC® NRS 3.1 Index pain subscale score of 4 to 10 in the index knee at Screening AND a minimum pain score of 4 on either of the individual questions of pain on walking on a flat surface or pain on climbing stairs at Screening.
- Average WOMAC® NRS 3.1 Index function subscale score of 4 to 10 in the index knee at Screening.
- Body mass index of ≥18.0 to ≤39.0 kg/m2
- Willing to stop treatment with oral and topical NSAIDs, and all other systemic pain medications (except acetaminophen/paracetamol per rescue protocol) from 2 weeks before Day 1 to end of study.
Exclusion Criteria
- Documented or reported history of increased bleeding in the absence of anticoagulant or antiplatelet drugs or prior history of major bleeding episode in the presence of anticoagulant or antiplatelet therapy.
- History of idiopathic or immune-mediated thrombocytopenia including history of or laboratory confirmed HIT (positive or equivocal antibodies against platelet factor 4 [ie, PF4] and positive Serotonin Release Assay [SRA]).
- Currently active or recent history (within preceding 12 months) of a gastric or duodenal ulcer, or suspicion of gastrointestinal tract bleeding.
- History of other bleeding disorders including haemophilia
- Recent cerebral bleeding or operation on brain, spine, or eyes within 6 months of Day 1
- Fibromyalgia or other moderate to severe pain 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 joint, including inflammatory joint disease such as rheumatoid arthritis, seronegative spondyloarthropathy (eg, ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease-related arthropathy), crystalline disease (eg, 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.
- 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), Gilberts syndrome, uncontrolled diabetes and uncontrolled hypothyroidism or hyperthyroidism, or mental or emotional disorders that preclude reliable study participation.
- Current treatment with anticoagulants or antiplatelet drugs, excluding aspirin ≤100 mg/day.
- Previous treatment with PPS in any form.
- 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
- Any clinically significant abnormalities on clinical chemistry, haematology, urinalysis, physical examination, medical history, 12-lead ECG, or vital signs as judged by the Investigator (at Screening).
- Major surgery or anticipated surgery during the study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 15 Mar 2023 | 40 |
 Czechia | Not Recruiting | 15 Mar 2023 | 20 |
 Poland | Not Recruiting | 15 Mar 2023 | 20 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Synacthen 0,25 mg/ml oplossing voor injectie | Other | OPLOSSING VOOR INJECTIE | SOLUTION FOR INJECTION | 0.25 | 8 | PRD5191129 |
Sodium Chloride 0.9% w/v for injection | Placebo | N/A | — | — | — | N/A |
Paracetamol Aurovitas, 500 mg, tabletki | Other | TABLETS | ORAL | 3 | 8 | PRD5963763 |
Paracetamol Teva 500 mg Tabletten | Other | TABLETTEN | ORAL | 3 | 8 | PRD4167092 |
PARALEN 500 mg tablety | Other | TABLETY | ORAL | 3 | 8 | PRD2856011 |
Pentosan polysulfate sodium | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS | 2.0 | 6 | PRD9539511 |
Panadol Novum 500 mg potahované tablety | Other | POTAHOVANÉ TABLETY | ORAL | 3 | 8 | PRD309060 |
Paracetamol Biofarm, 500 mg, tabletki | Other | TABLETKI | ORAL | 3 | 8 | PRD7394343 |
Paracetamol Accord, 500 mg, tabletki | Other | TABLETKI | ORAL | 3 | 8 | PRD4372207 |