What side effects are associated with this type of intervention?

Common treatments for osteoarthritis, such as NSAIDs, corticosteroids, and disease-modifying osteoarthritis drugs (DMOADs), have various side effects. NSAIDs can cause gastrointestinal issues, cardiovascular risks, and renal problems. Corticosteroids, when used intraarticularly, may lead to joint infection, cartilage damage, and systemic effects like increased blood sugar levels. Pentosan Polysulfate Sodium (PPS), which has anti-inflammatory and cartilage-protective effects, is associated with potential side effects such as gastrointestinal disturbances and, with long-term use, retinal disorders. Patients should discuss these risks with their healthcare provider to make informed treatment decisions.

What prior FDA approvals exist?

The FDA has approved several treatments for osteoarthritis, primarily focusing on pain relief and inflammation reduction. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, and diclofenac are commonly used for their anti-inflammatory properties. Additionally, corticosteroid injections are approved for short-term pain relief in severe cases. While Pentosan Polysulfate Sodium (PPS) is being studied for its potential anti-inflammatory and cartilage-protective effects, other similar treatments like hyaluronic acid injections aim to provide joint lubrication and pain relief. However, no specific FDA-approved drugs currently target cartilage protection as their primary mechanism of action for osteoarthritis.

What other types of research exist?

Promising alternatives to Pentosan Polysulfate Sodium (PPS) for osteoarthritis treatment include: 1) Cyclodextrin Polysulphate (CDPS), which has shown chondroprotective effects in rabbit models of osteoarthritis. 2) Polysulfated Glycosaminoglycan (PSGAG) and Sodium Hyaluronan, both of which have demonstrated clinical, biochemical, and histologic benefits in horse models of osteoarthritis. 3) Glycosaminoglycan Polysulfuric Acid Ester, which has shown efficacy in both rabbit and canine models of osteoarthritis by reducing cartilage degradation and improving morphological variables of disease severity.

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Glycosaminoglycan (GAG) Analog

Pentosan Polysulfate Sodium Injections for Osteoarthritis

Phase 2 & 3

Recruiting

Led By Thomas Schnitzer

Research Sponsored by Paradigm Biopharmaceuticals USA (INC)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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 1986 criteria.

Must not have

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]).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up stage 1: day 1, 15 and 39 - pre-dose and 2, 4, and 6 hours. pre-dose on days 4, 8, 11, 18, 22, 25, 29, 32 and 36

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

Summary

This trial tests if a new treatment can reduce pain and improve function in people with knee osteoarthritis. The medication aims to reduce inflammation and help repair knee joint damage.

Who is the study for?

Adults with knee osteoarthritis pain unresponsive to standard treatments, who have a BMI of 18-35 kg/m2 and can give informed consent. They must not be using certain medications or have conditions that could interfere with the study, such as recent surgery, other joint diseases, or severe allergies.

What is being tested?

The trial is testing if injections of Pentosan Polysulfate Sodium (PPS) are better than placebo at reducing knee pain in osteoarthritis. Participants will receive either PPS once or twice weekly, or a placebo for six weeks and will visit the clinic twice weekly during treatment.

What are the potential side effects?

Possible side effects from PPS may include bleeding issues due to its blood-thinning properties, gastrointestinal problems like stomach upset, allergic reactions for those sensitive to heparin-like drugs, liver enzyme changes, and potential hypersensitivity.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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I have been diagnosed with osteoarthritis in my knee.

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My knee arthritis is confirmed by X-ray to be moderate to severe.

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Painkillers like acetaminophen don't work for me or I can't take them.

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Painkillers like ibuprofen haven’t helped my pain or I can't take them.

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My knee pain scores between 4 to 10 and hurts when I walk or climb stairs.

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I am 18 years old or older.

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I have been diagnosed with osteoarthritis in my knee.

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My knee arthritis is confirmed by X-ray to be moderate to severe.

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Painkillers like ibuprofen haven’t helped my pain or I can't take them.

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My knee pain scores between 4 to 10 and hurts when I walk or climb stairs.

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I agree to stop taking NSAIDs and pain medications except acetaminophen 2 weeks before the study starts until it ends.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of bleeding easily without taking blood thinners.

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I have a history of low platelet counts due to an immune response.

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I have had osteonecrosis or a fracture due to osteoporosis.

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I am allergic to or cannot have Gadolinium contrast agents.

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I am allergic to or cannot take Tetracosactide.

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I have not had any cancer except for basal cell carcinoma in the last 5 years.

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I am taking blood thinners or anti-clotting medications, but not more than 100 mg of aspirin daily.

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I have been treated with PPS before.

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I haven't used strong immune system altering drugs recently, except for minor hydrocortisone cream use.

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I have not taken bisphosphonates in the last 12 weeks.

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I have not used denosumab or iloprost in the last 12 weeks.

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I have taken steroids for OA or other reasons within the last 8 weeks.

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I have not taken Megestrol Acetate in the last 6 weeks.

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I am not taking any medications that change my sodium or potassium levels.

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I do not have active hepatitis B or C, or uncontrolled HIV.

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My knee X-rays show no severe misalignment, chondrocalcinosis, other joint diseases, bone diseases, tumors, or fractures.

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My blood pressure is high, but it has been stable for at least a month.

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I am mostly confined to bed or a wheelchair and cannot care for myself.

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I have not had major surgery recently nor do I plan any during the study.

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I am not in the hospital nor do I plan to be during the study.

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I am planning to have total knee reconstruction during the study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ stage 1: day 1, 15 and 39 - pre-dose and 2, 4, and 6 hours. pre-dose on days 4, 8, 11, 18, 22, 25, 29, 32 and 36

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~stage 1: day 1, 15 and 39 - pre-dose and 2, 4, and 6 hours. pre-dose on days 4, 8, 11, 18, 22, 25, 29, 32 and 36

This trial's timeline: 3 weeks for screening, Varies for treatment, and stage 1: day 1, 15 and 39 - pre-dose and 2, 4, and 6 hours. pre-dose on days 4, 8, 11, 18, 22, 25, 29, 32 and 36 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Knee

Secondary study objectives

Key secondary: Change from baseline at Day 56 in function as assessed by the average functional subscale score of the WOMAC NRS 3.1 Index

Key secondary: Change from baseline at Day 84 in function as assessed by the average functional subscale score of the WOMAC NRS 3.1 Index

Key secondary: Change from baseline at Day 84 in knee pain as assessed by the average pain subscale score of the WOMAC NRS 3.1 Index

+19 more

Other study objectives

Exploratory: Change in bone shape on MRI from baseline at Day 168

Magnetic Resonance Imaging

Exploratory: Change in joint space width on MRI from baseline at Day 168

+10 more

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

Trial Design

4Treatment groups

Experimental Treatment

Placebo Group

Group I: PPS Twice WeeklyExperimental Treatment1 Intervention

Pentosan Polysulfate Sodium (PPS) twice weekly for 6 weeks

Group II: PPS Once WeeklyExperimental Treatment2 Interventions

Pentosan Polysulfate Sodium (PPS) + placebo once weekly for 6 weeks

Group III: PPS Fixed Dose Once WeeklyExperimental Treatment2 Interventions

Pentosan Polysulfate Sodium (PPS) Fixed dose (100mg,150mg, or 180mg) once weekly + placebo once weekly for 6 weeks

Group IV: PlaceboPlacebo Group1 Intervention

Placebo twice weekly for 6 weeks

0 / 33Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Osteoarthritis (OA) include NSAIDs, which reduce inflammation and pain by inhibiting cyclooxygenase enzymes (COX-1 and COX-2). Platelet-rich plasma (PRP) injections aim to promote tissue repair and reduce inflammation through growth factors. Pentosan Polysulfate Sodium (PPS) exhibits anti-inflammatory and cartilage-protective effects by inhibiting enzymes that degrade cartilage and promoting the synthesis of proteoglycans and collagen. These mechanisms are crucial for OA patients as they help manage pain, reduce inflammation, and potentially slow the progression of cartilage degradation, thereby improving joint function and quality of life.

Polysulphated polysaccharides: an in vitro study of their effects on proteoglycan biosynthesis by articular chondrocytes.Pentosan polysulfate inhibits IL-1β-induced iNOS, c-Jun and HIF-1α upregulation in canine articular chondrocytes.Osteoarthritis, genetic and molecular mechanisms.