Treatment Effects of Subcutaneous Injections of Pentosan Polysulfate Sodium vs Placebo in Participants With Knee OA Pain

NCT04809376 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PARA_OA_002
• Study Type: interventional
• Target: 602
• Locations: 2 countries
• Sites: 33

Brief 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 31 weeks per participant
• The treatment duration will be 6 weeks.
• The visit frequency will be twice weekly during treatment.
• The visit frequency will be every 4 weeks during the follow-up period.

Conditions

Osteoarthritis, Knee

Keywords

Osteoarthritis; Knee

Outcome Measures

Primary Outcomes (1)

• Change from baseline at Day 56 in knee pain as assessed by the average pain sub-scale score of the WOMAC® NRS 3.1 Index.

  WOMAC: The WOMAC® NRS 3.1 Index is a validated, self-administered, health status questionnaire that assesses pain, stiffness, and function in patients with hip or knee OA . The WOMAC pain sub-scale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint (knee) during the past 48 hours. It is calculated as the mean of scores from 5 individual questions scored on a numerical rating scale (NRS). Scores for each question and WOMAC Pain sub-scale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain.

  Baseline, Day 56

Secondary Outcomes (22)

• 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

  Baseline to Day 56

• 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

  Baseline to Day 84

• 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

  Baseline to Day 84

• Stage 1 only: Change from baseline at Day 56 and 84 in knee pain as assessed by the average pain subscale score of the WOMAC NRS 3.1 Index for PPS 1.5 mg/kg twice weekly, PPS 2.0mg/kg once weekly, and PPS fixed dose once weekly

  Baseline to Day 56 and Day 84

• Stage 1 only: Reduction in knee pain of ≥ 30% and ≥ 50% as assessed by the average pain subscale score of the WOMAC NRS 3.1 Index at Days 56 and 84 for PPS 1.5mg/kg twice weekly, PPS 2.0mg/kg once weekly, and PPS fixed dose once weekly

  Baseline to Day 56 and Day 84

Other Outcomes (13)

• Exporatory: Number of participants with an Anti-Drug-Antibody (ADA) response after treatment

  Baseline, Days 11, 25, 39, 56 and 84

• Exploratory: Correlation of Anti-Drug-Antibody (ADA) response with clinical events

  Baseline, Days 11, 25, 39, 56, and 84

• Exploratory: PPS PK profile of single and multiple doses based on sparse blood sampling

  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

Study Arms (4)

PPS Twice Weekly

EXPERIMENTAL

Pentosan Polysulfate Sodium (PPS) twice weekly for 6 weeks

Drug: Pentosan Polysulfate Sodium twice weekly

PPS Once Weekly

EXPERIMENTAL

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

Drug: Placebo (Sodium Chloride Injection, 0.9%); Drug: Pentosan Polysulfate Sodium once weekly

PPS Fixed Dose Once Weekly

EXPERIMENTAL

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

Drug: Placebo (Sodium Chloride Injection, 0.9%); Drug: Pentosan Polysulfate Sodium Fixed Dose

Placebo

PLACEBO COMPARATOR

Placebo twice weekly for 6 weeks

Drug: Placebo (Sodium Chloride Injection, 0.9%)

Interventions

Pentosan Polysulfate Sodium twice weekly DRUG

Subcutaneous Injection, 1.5mg/kg Ideal body Weight (IBW)

Also known as: PPS twice weekly

PPS Twice Weekly

Placebo (Sodium Chloride Injection, 0.9%) DRUG

Placebo to match PPS

Also known as: Placebo

PPS Fixed Dose Once Weekly; PPS Once Weekly; Placebo

Pentosan Polysulfate Sodium Fixed Dose DRUG

Subcutaneous Injection, 100/150/180 mg if \<65kg/ ≥ 65 kg and ≤ 90kg/ \>90 kg IBW

Also known as: Fixed Dose

PPS Fixed Dose Once Weekly

Pentosan Polysulfate Sodium once weekly DRUG

Subcutaneous Injection, 2.0mg/kg Ideal body Weight (IBW)

Also known as: PPS once weekly

PPS Once Weekly

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:
• 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
• 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 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.
• Average WOMAC NRS 3.1 Index function sub-scale score of 4 to 10 in the index knee at Screening.
• Body mass index of \>=18 to \<=39.0 kg/m2
• Female subjects of childbearing potential and Male subjects must agree to comply with protocol specified contraceptive requirements
• 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 (excluding knee brace) 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, 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.

You may not qualify if:

• 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.
• Spinal anaesthesia within 14 days of Day 1,
• 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.
• 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
• Allergy or contraindication to Tetracosactide
• 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), uncontrolled diabetes and uncontrolled hypothyroidism or hyperthyroidism, or mental or emotional disorders that preclude reliable study participation.
• History of pituitary irradiation or recent (within 1 year) history of transsphenoidal surgery
• Any cancer within the previous 5 years, except for basal cell carcinomas.

Sponsors & Collaborators

• Paradigm Biopharmaceuticals USA (INC): lead

Study Sites (33)

Alliance for Multispecialty Research - Tempe

Tempe, Arizona, 85281, United States

Location

Fiel Family and Sports Medicine

Tempe, Arizona, 85283, United States

Location

Tucson Orthopaedic Institute

Tucson, Arizona, 85712, United States

Location

Core Healthcare Group

Cerritos, California, 90703, United States

Location

Biosolutions Clinical Research Center

La Mesa, California, 91942, United States

Location

Providence Clinical Research

North Hollywood, California, 91606, United States

Location

Prospective Research Innovations Inc.

Rancho Cucamonga, California, 91730, United States

Location

Encompass Clinical Research

Spring Valley, California, 91978, United States

Location

Clinical Research of West Florida- Clearwater

Clearwater, Florida, 33765, United States

Location

University Clinical Research-Deland

DeLand, Florida, 32720, United States

Location

LMG Research

Miami, Florida, 33125, United States

Location

Well Pharma Medical Research, Corp.

Miami, Florida, 33173, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Clinical Research of West Florida

Tampa, Florida, 33606, United States

Location

Conquest Research

Winter Park, Florida, 32789, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Alliance for Multispecialty Research - Newton

Newton, Kansas, 67114, United States

Location

Alliance for Multispecialty Research - Wichita West

Wichita, Kansas, 67205, United States

Location

Alliance for Multispecialty Research - Wichita East

Wichita, Kansas, 67207, United States

Location

Tandem Clinical Research

Marrero, Louisiana, 77072, United States

Location

Alliance for Multispecialty Research - Las Vegas

Las Vegas, Nevada, 89119, United States

Location

Kaplan Medical Research

Las Vegas, Nevada, 89119, United States

Location

Coastal Carolina Research Center

North Charleston, South Carolina, 29405, United States

Location

Alliance for Multispecialty Research - Knoxville

Knoxville, Tennessee, 37909, United States

Location

FutureSearch Trials - Austin

Austin, Texas, 78731, United States

Location

Clinical Investigations of Texas

Plano, Texas, 75075, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

Diagnostics Research Group - Northwest San Antonio

San Antonio, Texas, 78229, United States

Location

Discovery Clinical Trials

San Antonio, Texas, 78258, United States

Location

Australian Clinical Research Network

Maroubra, New South Wales, 2035, Australia

Location

Griffith University

Southport, Queensland, 4222, Australia

Location

Sportsmed

Stepney, South Australia, 5069, Australia

Location

Linear Clinical Research Limited

Nedlands, Western Australia, 6009, Australia

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Interventions

Sodium Chloride; Pentosan Sulfuric Polyester

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Organic Chemicals; Polysaccharides; Carbohydrates

Study Officials

• Thomas Schnitzer

  Northwestern University Feinberg School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2021
• First Posted: March 22, 2021
• Study Start: October 19, 2021
• Primary Completion: October 15, 2024
• Study Completion: January 6, 2025
• Last Updated: April 8, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (29); AU (4)