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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04809376




Registration number
NCT04809376
Ethics application status
Date submitted
18/03/2021
Date registered
22/03/2021

Titles & IDs
Public title
Treatment Effects of Subcutaneous Injections of Pentosan Polysulfate Sodium vs Placebo in Participants With Knee OA Pain
Scientific title
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 Pain
Secondary ID [1] 0 0
PARA_OA_002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoarthritis, Knee 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pentosan Polysulfate Sodium twice weekly
Treatment: Drugs - Placebo (Sodium Chloride Injection, 0.9%)
Treatment: Drugs - Pentosan Polysulfate Sodium Fixed Dose
Treatment: Drugs - Pentosan Polysulfate Sodium once weekly

Experimental: PPS Twice Weekly - Pentosan Polysulfate Sodium (PPS) twice weekly for 6 weeks

Experimental: PPS Once Weekly - Pentosan Polysulfate Sodium (PPS) + placebo once weekly for 6 weeks

Experimental: PPS Fixed Dose Once Weekly - Pentosan Polysulfate Sodium (PPS) Fixed dose (100mg,150mg, or 180mg) once weekly + placebo once weekly for 6 weeks

Placebo comparator: Placebo - Placebo twice weekly for 6 weeks


Treatment: Drugs: Pentosan Polysulfate Sodium twice weekly
Subcutaneous Injection, 1.5mg/kg Ideal body Weight (IBW)

Treatment: Drugs: Placebo (Sodium Chloride Injection, 0.9%)
Placebo to match PPS

Treatment: Drugs: Pentosan Polysulfate Sodium Fixed Dose
Subcutaneous Injection, 100/150/180 mg if \<65kg/ = 65 kg and = 90kg/ \>90 kg IBW

Treatment: Drugs: Pentosan Polysulfate Sodium once weekly
Subcutaneous Injection, 2.0mg/kg Ideal body Weight (IBW)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Day 56
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Baseline to Day 56
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Baseline to Day 84
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Baseline to Day 84
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Baseline to Day 56 and Day 84
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Baseline to Day 56 and Day 84
Secondary outcome [6] 0 0
Stage 1 only: Stage 1 only: Change from baseline at Day 56 and 84 in function as assessed by the average functional 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
Timepoint [6] 0 0
Baseline to Day 56 and Day 84
Secondary outcome [7] 0 0
Stage 1 only: Improvement in function of = 30% and = 50% as assessed by the average functional 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
Timepoint [7] 0 0
Baseline to Day 56 and Day 84
Secondary outcome [8] 0 0
Stage 1 only: PGIC scores at Days 56 and 84 for PPS 1.5mg/kg twice weekly, PPS 2.0mg/kg once weekly, and PPS fixed dose once weekly
Timepoint [8] 0 0
Baseline to Day 56 and Day 84
Secondary outcome [9] 0 0
Stage 1 and 2: Outcomes Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index response rate at Days 39, 56, 84, 112, 140, and 168
Timepoint [9] 0 0
Baseline, Days 39, 56, 84, 112, 140 and 168
Secondary outcome [10] 0 0
Stage 1 and 2: Change from baseline at Days 11, 25, 39, 112, 140 and 168 in knee pain as assessed by the average pain sub-scale score of the WOMAC® NRS 3.1 Index.
Timepoint [10] 0 0
Baseline, Days 11, 25, 39, 112, 140 and 168
Secondary outcome [11] 0 0
Stage 1 and 2: Change from baseline in knee pain of >=30% and >=50% as assessed by the average pain sub-scale score of the WOMAC® NRS 3.1 Index at Days 11, 25, 39, 112, 140, and 168
Timepoint [11] 0 0
Baseline, Days 11, 25, 39, 112, 140 and 168
Secondary outcome [12] 0 0
Stage 1 and 2: Change from baseline at Days 11, 25, 39, 112, 140 and 168 in function as assessed by the average functional sub-scale score of the WOMAC® Index.
Timepoint [12] 0 0
Baseline, Days 11, 25, 39, 112, 140 and 168
Secondary outcome [13] 0 0
Stage 1 and 2: Improvement in function of >=30% and >=50% as assessed by the average functional sub-scale score of the WOMAC® NRS 3.1 Index from baseline at Days 11, 25, 39, 112, 140, and 168
Timepoint [13] 0 0
Baseline, Days 11, 25, 39, 112, 140, and 168
Secondary outcome [14] 0 0
Stage 1 and 2: Change from baseline at Days 11, 25, 39, 56, 84, 112, 140, and 168 in knee stiffness as assessed by the average stiffness sub-scale score of the WOMAC® NRS 3.1 Index
Timepoint [14] 0 0
Baseline, Days 11, 25, 39, 56, 84, 112, 140, and 168
Secondary outcome [15] 0 0
Stage 1 and 2: Change from baseline at Days 11, 25, 39, 56, 84, 112, 140, and 168 overall as assessed by the overall score of WOMAC® NRS 3.1 Index
Timepoint [15] 0 0
Baseline, Days 11, 25, 39, 56, 84, 112, 140, and 168
Secondary outcome [16] 0 0
Stage 1 and 2: Change from baseline at Days 11, 25, 39, 56, 84, 112, 140, and 168 in Quality of Life (QoL) as assessed by Short Form-36 General Health Survey (SF-36)
Timepoint [16] 0 0
Baseline, Days 11, 25, 39, 56, 84, 112, 140, and 168
Secondary outcome [17] 0 0
Stage 1 and 2: PGIC scores at Days 39, 112, 140, and 168
Timepoint [17] 0 0
Baseline, Days 39, 112, 140, and 168
Secondary outcome [18] 0 0
Stage 1 and 2: Change from baseline at Days 56, 84, 112, 140, and 168 in Work Productivity and Activity Impairment (WPAI) questionnaire score
Timepoint [18] 0 0
Baseline, Day 56, 84, 112, 140 and 168
Secondary outcome [19] 0 0
Stage 1 and 2: Number of days of rescue medication used from Day 1 to Day 168
Timepoint [19] 0 0
Baseline up to Day 168
Secondary outcome [20] 0 0
Stage 1 and 2: Incidence of treatment-emergent Adverse Event (TEAEs), including serious AEs (SAEs)
Timepoint [20] 0 0
Baseline up to Day 168
Secondary outcome [21] 0 0
Stage 1 and 2: Treatment-emergent clinical laboratory abnormalities
Timepoint [21] 0 0
Baseline up to Day 168
Secondary outcome [22] 0 0
Stage 1 and 2: Clinically significant changes in electrocardiograms (ECG) compared with baseline (pharmacokinetic [PK] subset only)
Timepoint [22] 0 0
Baseline, Day 1, Day 15, Day 36 and Day 39

Eligibility
Key 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 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:

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 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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] 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.
* Current hyperkalemia and/or hyponatremia.
* History or current autoimmune polyglandular syndromes
* 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 (with immunosuppressive effects) systemic therapy including but not limited to oral, inhaled, intranasal, intra-articular and topical corticosteroids (occasional use of topical, inhaled or intranasal corticosteroids is acceptable).
* Use of opioids within 6 weeks before Day 1.
* 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 8 weeks before Day 1.
* Intra-articular injections to the index knee: steroids within 24 weeks; hyaluronic acid or any other intra-articular injections within 24 weeks before Day 1.
* Cannabinoids within 30 days 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.
* 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
* Treatment with dehydroepiandrosterone sulfates within 6 weeks before Day 1.
* Chronic use of oral glucocorticoid receptor antagonists or cortisol synthesis inhibitors within12 weeks before Day 1.
* Biotin within 72 hours of screening.
* Megestrol Acetate within 6 weeks before Day 1
* Current treatment with any medication that may lead to Maculopathy (see Table 3)
* Any medication that alters sodium and/or potassium levels (see Table Prohibited Therapy)
* 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]) > 36 seconds, 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.
* Evidence of pigmentary maculopathy identified by a retinal specialist during Screening.
* Morning Cortisol = 3 µg/dL.
* ACTH <10 pg/ml; Morning Cortisol >3 µg/dL and <10 µg/dL and peak cortisol (by ACTH stimulation test) <18 µg/dL.
* 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.
* 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/10/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
6/01/2025
Actual
Sample size
Target
Accrual to date
Final
602
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
Australian Clinical Research Network - Maroubra
Recruitment hospital [2] 0 0
Griffith University - Southport
Recruitment hospital [3] 0 0
Sportsmed - Stepney
Recruitment hospital [4] 0 0
Linear Clinical Research Limited - Nedlands
Recruitment postcode(s) [1] 0 0
2035 - Maroubra
Recruitment postcode(s) [2] 0 0
4222 - Southport
Recruitment postcode(s) [3] 0 0
5069 - Stepney
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Nevada
Country [8] 0 0
United States of America
State/province [8] 0 0
South Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Paradigm Biopharmaceuticals USA (INC)
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Thomas Schnitzer
Address 0 0
Northwestern University Feinberg School of Medicine
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04809376