Treatment Effects of Subcutaneous Injections of Pentosan Polysulfate Sodium Versus Placebo in Participants With Knee Osteoarthritis Pain

• Status: Not yet recruiting
• Trial end date: 2023-01-06
• Target enrollment: 0
• Participant gender: All

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 osteoarthritis pain.

Study details include:

• The study duration will be up to 28 weeks per participant

• The treatment duration will be 6 weeks.

• The visit frequency will be twice weekly during treatment..

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Paradigm Biopharmaceuticals USA (INC)
• Treatments: Pentosan Sulfuric Polyester

Criteria

Inclusion Criteria:

• 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 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 (ie, the participant still experiences pain) to conservative therapy for >=6 months preceding Screening, defined as history indicating that:

1. Acetaminophen/paracetamol therapy has not provided sufficient pain relief or participant is unable to take acetaminophen/paracetamol chronically/long term because of contraindication or inability to tolerate; AND

2. At least 1 oral non-steroidal anti-inflammatory drug (NSAID, including cyclooxygenase-2 inhibitors) and/or topical NSAID therapy that has not provided sufficient pain relief or participant is unable to take NSAIDs because of contraindication or inability to tolerate.

• Average WOMAC NRS 3.1 Index pain sub-scale score of 4 to 10 in the index knee at Screening AND Day 1 AND a minimum pain score of 4 on either of the individual WOMAC NRS 3.1 Index questions of pain on walking on a flat surface or pain on climbing stairs at Screening AND Day 1.

• Average WOMAC NRS 3.1 Index function sub-scale score of 4 to 10 in the index knee at Screening and Day 1.

• Body mass index of >=18 to <=39.0 kg/m2

• 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.

• Current non-pharmacologic treatment regimen for knee OA 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, opioids, and all other systemic pain medications (except acetaminophen/paracetamol per rescue protocol) 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.

• Female subjects of childbearing potential and Male subjects must agree to comply with protocol specified contraceptive requirements

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]).

• Currently active or recent history (within preceding 12 months) of a gastric or duodenal ulcer, or suspicion of gastrointestinal tract bleeding.

• Fibromyalgia, regional pain caused by lumbar or cervical compression with radiculopathy, 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 osteonecrosis or osteoporotic fracture (ie, a participant with a history of osteoporosis and a minimally traumatic or atraumatic fracture).

• History of hypersensitivity to PPS, heparin or heparin-like drugs, or drugs of a similar chemical or pharmacological class.

• Current clinically significant medical conditions, medical history, physical findings, or laboratory abnormality that, in the Investigator's opinion, makes the participant unsuitable for the study. Chronic medical conditions will be allowed at the discretion of the Investigator but must be stable without necessitating medication changes within 30 days before Day 1.

• 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 protocol.

• Current treatment with anticoagulants or antiplatelet drugs, excluding aspirin <=100 mg/day.

• Previous treatment with PPS in any form.

• Current or recent (within 90 days before Day 1) immunosuppressive or immunomodulatory systemic therapy as follows:

1. Chronic use of corticosteroids: >=15 mg/day of oral prednisolone or equivalent daily,

2. Intermittent corticosteroids: >=40 mg/day of oral prednisolone or equivalent for 1 or more short courses of >3 days.

• Use of bisphosphonates within 12 weeks before Day 1.

• Use of denosumab and 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, and orally for OA or other indications within 2 weeks before Day 1.

• Intra-articular injections to the index knee: steroids within 12 weeks; hyaluronic acid or any other intra-articular injections within 24 weeks before Day 1.

• Use of 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.

• 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]) > upper limit of normal (ULN), platelets <150,000/µL, or liver enzyme tests (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) >=2 × ULN at Screening.

• 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.

• Radiographic evidence of any of the following conditions in any Screening radiograph:

excessive malalignment of the knee, severe chondrocalcinosis; other arthropathies (eg, rheumatoid arthritis, psoriatic arthritis, gout), systemic metabolic bone disease (eg, Paget's disease, metastatic calcifications), primary or metastatic tumour lesions, stress, or traumatic fracture.

• Radiographic evidence of any of the following conditions at Screening:

1. subchondral insufficiency fractures

2. spontaneous osteonecrosis of the knee

3. osteonecrosis

4. pathologic fracture

• 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).

• 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 anti-hypertensive 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.

• Largely or wholly incapacitated (eg, bedridden or confined to a wheelchair, permitting little or no self-care).

• Major surgery or anticipated surgery during the study.

• Currently hospitalized 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.

• Contraindication to MRI scans.

• An employee of the Sponsor, clinical research organisations 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.