A 2-stage, Adaptive, Randomised, Double-blind, Placebo-controlled, Multicentre Study to Evaluate Dose and Treatment Effect of Pentosan Polysulfate Sodium Compared with Placebo in Participants with Knee Osteoarthritis Pai

Phase 1

• Conditions: Knee osteoarthritis pain; MedDRA version: 21.1Level: LLTClassification code: 10023476Term: Knee osteoarthritis Class: 10028395; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: CTIS2022-500228-31-00
• Lead Sponsor: Paradigm Biopharmaceuticals (USA) Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-03-16
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 898

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 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 function subscale score of 4 to 10 in the index knee at Screening., Body mass index of =18.0 to =35.0 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., 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., History of idiopathic or immune-mediated thrombocytopenia including history of or laboratory confirmed HIT (positive or equivocal antibodies against platelet factor 4 [ie, PF4])., 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the treatment effect of PPS on knee pain and function in participants with knee OA pain.;Secondary Objective: To evaluate the treatment effect of PPS on knee pain and function in participants with knee OA pain. for European Medicines Agency [EMA] / Medicines and Health Product Regulatory Agency (MHRA), function will be included as a co-primary endpoint, but still tested in hierarchical order;Primary end point(s): 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., Change from baseline at Day 56 in function as assessed by the average functional subscale score of the WOMAC® NRS 3.1 Index for EMA/MHRA, function will be included as a co-primary endpoint, but still tested in hierarchical order).

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Change from baseline at Day 56 in function as assessed by the average functional subscale score of the WOMAC® NRS 3.1 Index for EMA/MHRA, function will be included as a co-primary endpoint, but still tested in hierarchical order).Function will be a key secondary in the United States;Secondary end point(s):Change from baseline at Day 84 in knee pain as assessed by the average pain subscale score of the WOMAC® NRS 3.1 Index.;Secondary end point(s):Change from baseline at Day 84 in function as assessed by the average functional subscale score of the WOMAC® NRS 3.1 Index.