Treatment and Duration Effect of Pentosan Polysulfate Sodium (PPS) in Participants With Knee Osteoarthritis Pain

An Observational Follow-up Study to Investigate the Duration of Treatment Effect With Subcutaneous Injections of Pentosan Polysulfate Sodium Compared With Placebo in Adult Participants With Knee Osteoarthritis Pain

The purpose of this study is to measure the duration of treatment effect with subcutaneous injections of pentosan polysulfate sodium (PPS) compared with placebo in adult participants with knee osteoarthritis (OA) pain. The study duration will be up to 34 weeks.

Participants who completed pDay 162 of Study PARA_OA_002 (i.e. did not discontinue/withdraw prematurely from the parent study) will be invited to participate.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: Placebo (Sodium Chloride Injection, 0.9%); Drug: Pentosan Polysulphate Sodium

Detailed Description

This is an observational study to determine duration of treatment effect and assess long-term safety up to 52 weeks post PPS use for 6 weeks in parent study (PARA_OA_002). The duration of treatment effect will be evaluated by the OMERACT-OARSI responder criteria for knee OA.

Eligible participants will be enrolled in Study PARA_OA_006 at the completion of the parent study PARA_OA_002. There will be no intervention in this observational study.

Participants will attend screening (visit 1), three phone visits at 8, 16, and 24 weeks, and an EOS (end of study) visit 34 weeks at the site, a total of 5 visits. Participants questionnaires include WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) NRS 3.1 Index, PGIC (Patients Global Impression of Change), WPAI (Work Productivity and Activity Impairment) and quality of life SF-36.

• Study Type: Observational
• Enrollment (Actual): 133
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Camberwell, Victoria, Australia, 3124
      • Emeritus Research
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants who completed pDay 168 of Study PARA_OA_002 (ie, did not discontinue/withdraw prematurely from the parent study).

Description

Inclusion Criteria:

• Participants who completed Day 168 of Study PARA_OA_002 (ie, did not discontinue/withdrew prematurely from the parent study).
• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pentosan Polysulfate Sodium; Pentosan Polysulfate Sodium (PPS) at Dose and frequency selected in Stage 1 of Parent Study for 6 weeks	Drug: Pentosan Polysulphate Sodium; Subcutaneous Injection (100mg/ml); Other Names: PPS
Placebo; Placebo for 6 weeks	Drug: Placebo (Sodium Chloride Injection, 0.9%); Placebo to match PPS; Other Names: Sodium Chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess duration of treatment effect of PPS in participants with OA pain	Time from initial response in the parent study (PARA_OA_002) to loss of OMERACT-OARSI (Outcomes Measures in Rheumatology - Osteoarthritis Research Society International) response.	From initial response time baseline in parent study up to 34 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline of the parent study in Work Productivity and Activity Impairment (WPAI) questionnaire.	This 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	Baseline (parent study) pDay1, Weeks 8, 16, 24 and 34
Assess duration of treatment effect of PPS in participants with OA pain	Percentage of participants considered OMERACT- OARSI (Outcomes Measures in Rheumatology - Osteoarthritis Research Society International) responders at each timepoint..	Week 8, 16, 24, and 34
Assess efficacy of PPS treatment on knee pain in participants with knee OA pain	WOMAC NRS 3.1 (Western Ontario and McMaster Universities Osteoarthritis Index) Index Pain average subscale score. Reduction in knee pain of ≥30% and ≥50% as assessed by the average pain WOMAC NRS 3.1 subscale score. Ranges 0-10 with 0 represents no pain and 10 represents extreme pain.	Baseline (parent study) pDay1, weeks 8, 16, 24, and 34
WOMAC NRS 3.1 (Western Ontario and McMaster Universities Osteoarthritis Index) assessment of knee function in participants with knee OA pain	WOMAC NRS 3.1 Index Function WOMAC NRS 3.1 Index.. Improvement of function assessed of ≥30% and ≥50% as assessed by the average Function subscale score (knee) during the past 48 hours. Ranges Scoring 0-10, 0 is better or none and 10 is worse.	Baseline (parent study) pDay1, weeks 8, 16, 24, and 34
WOMAC NRS 3.1 (Western Ontario and McMaster Universities Osteoarthritis Index) knee stiffness assessment in participants with knee OA	WOMAC NRS 3.1 Index Stiffness average subscale score. Ranges 0-10, 0 is better or none and 10 is extreme or worse.	Baseline (parent study) pDay1, weeks 8, 16, 24, and 34
Overall score WOMAC NRS 3.1 (Western Ontario and McMaster Universities Osteoarthritis Index) in participants with knee OA	WOMAC NRS 3.1 Index Overall average subscale score The WOMAC® NRS 3.1 Index consists of 24 questions and produces 3 sub-scales scores for pain (5 questions), stiffness (2 questions), and function (17 questions) and a total score that summarizes overall disability. Score of 0 is better and the higher score is worse	Baseline (parent study) pDay1, weeks 8, 16, 24, and 34
Assess effect of PPS on Patient Global Impression of Change (PGIC) in participants with knee OA pain	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".	Weeks 8, 16, 24 and 34
Change from baseline of the parent study in Quality of Life (QoL) as assessed by Short Form-36 General Health Survey (SF-36)	The SF-36 v2 is a 36-item, patient-reported survey of patient health, consisting of 8 scaled scores, which are the weighted sums of the questions in their section. The 1-week recall form asks the respondent to answer the questions as they pertain to the way he or she felt or acted during the past week. Score ranges 0-100 higher scores indicate better health.	Baseline (parent study) pDay1, Weeks 8, 16, 24 and 34
Assess real-world use of pain medications/therapies, following a single course of PPS	Number of days rescue medication used or use of other pain medications and therapies	Baseline up to Week 34
Incidence of treatment-emergent AE's, SAE's and AESI of PPS is participants with knee OA pain	Data of SAE's, AE's, causally to IP, AE's of Special Interest (AEST), AE's requiring any intervention for index knee pain and AE's requiring pain medication.	Baseline up to Week 34

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in joint synovitis/effusion volume on MRI	MRIs will be reviewed by an independent trained reader blinded to participant characteristics, study information and timing of MRI scans. All measurement will be done in duplicate	Baseline (parent study) pDay1 and at Week 34
Effect of PPS on Change in cartilage volume on MRI	MRIs will be reviewed by an independent trained reader blinded to participant characteristics, study information and timing of MRI scans. All measurement will be done in duplicate	Baseline (parent study) pDay1 and at Week 34
Change in bone shape on MRI and whether these correlate with clinical outcomes	MRIs will be reviewed by an independent trained reader blinded to participant characteristics, study information and timing of MRI scans. All measurement will be done in duplicate	Baseline (parent study) pDay1 and at Week 34
Change in joint space width on X-ray	X-Rays will be reviewed by an independent trained reader blinded to participant characteristics, study information and timing of MRI scans. All measurement will be done in duplicate	Baseline (parent study) pDay1 and at Week 34
Change in joint space width on MRI	MRIs will be reviewed by an independent trained reader blinded to participant characteristics, study information and timing of MRI scans. All measurement will be done in duplicate	Baseline (parent study) pDay1 and at Week 34
Explore any correlation between joint space width measurements from x-rays and MRI	MRIs and x-rays will be reviewed by an independent trained reader blinded to participant characteristics, study information and timing of MRI scans and x-rays. All measurement will be done in duplicate.	Week 34
Change in subchondral Bone Marrow Lesion (BML) on Magnetic Resonance Imaging (MRI) from baseline of the parent study.	MRIs will be reviewed by an independent trained reader blinded to participant characteristics, study information and timing of MRI scans. All measurement will be done in duplicate	Baseline (parent study) pDay1 and at Week 34

Collaborators and Investigators

• Sponsor: Paradigm Biopharmaceuticals Ltd.
• Investigators: Principal Investigator: Thomas Schnitzer, Northwestern University Feinberg School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2023
• Primary Completion (Actual): December 24, 2024
• Study Completion (Actual): December 24, 2024

Study Registration Dates

• First Submitted: March 18, 2021
• First Submitted That Met QC Criteria: March 22, 2021
• First Posted (Actual): March 24, 2021

Study Record Updates

• Last Update Posted (Actual): July 22, 2025
• Last Update Submitted That Met QC Criteria: July 17, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Osteoarthritis; Knee
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee; Anticoagulants; Pentosan Sulfuric Polyester
• Other Study ID Numbers: PARA_OA_006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No