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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Paradigm Biopharmaceuticals (USA) Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

31 Mar 2023 → 9 Nov 2023

Decision date (initial)

2023-02-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Paradigm Biopharmaceuticals (USA) Inc.

External identifiers

EU CT number

2022-500228-31-01

ClinicalTrials.gov

NCT04809376

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Dose response, Efficacy

To evaluate the treatment effect of PPS on knee pain and function in participants with knee OA pain.

Secondary objectives 1

1. To evaluate the treatment effect of PPS on knee pain and function in participants with knee OA pain. for European Medicines Agency [EMA] / Medicines and Health Product Regulatory Agency (MHRA), function will be included as a co-primary endpoint, but still tested in hierarchical order

Conditions and MedDRA coding

Knee osteoarthritis pain

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Male and Female Participants 18 years of age or older
2. Clinical diagnosis of OA in the index knee by American College of Rheumatology 1986 criteria.
3. 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.
4. Osteoarthritis pain in the index knee unresponsive to conservative therapy for ≥6 months preceding Screening
5. Average WOMAC® NRS 3.1 Index pain subscale score of 4 to 10 in the index knee at Screening AND a minimum pain score of 4 on either of the individual questions of pain on walking on a flat surface or pain on climbing stairs at Screening.
6. Average WOMAC® NRS 3.1 Index function subscale score of 4 to 10 in the index knee at Screening.
7. Body mass index of ≥18.0 to ≤39.0 kg/m2
8. 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.

Exclusion criteria 15

1. 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.
2. 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]).
3. Currently active or recent history (within preceding 12 months) of a gastric or duodenal ulcer, or suspicion of gastrointestinal tract bleeding.
4. History of other bleeding disorders including haemophilia
5. Recent cerebral bleeding or operation on brain, spine, or eyes within 6 months of Day 1
6. Fibromyalgia 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.
7. 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.
8. History of hypersensitivity to PPS, heparin or heparin-like drugs, or drugs of a similar chemical or pharmacological class.
9. 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.
10. 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), Gilberts syndrome, uncontrolled diabetes and uncontrolled hypothyroidism or hyperthyroidism, or mental or emotional disorders that preclude reliable study participation.
11. Current treatment with anticoagulants or antiplatelet drugs, excluding aspirin ≤100 mg/day.
12. Previous treatment with PPS in any form.
13. 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
14. 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).
15. Major surgery or anticipated surgery during the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change from baseline at Day 56 in knee pain as assessed by the average pain subscale score of the Western Ontario and McMaster Universities (Osteoarthritis Index) (WOMAC®) Numeric Rating Scale (NRS) 3.1 Index.
2. Change from baseline at Day 56 in function as assessed by the average functional subscale score of the WOMAC® NRS 3.1 Index for EMA/MHRA, function will be included as a co-primary endpoint, but still tested in hierarchical order).

Secondary endpoints 3

1. Change from baseline at Day 56 in function as assessed by the average functional subscale score of the WOMAC® NRS 3.1 Index for EMA/MHRA, function will be included as a co-primary endpoint, but still tested in hierarchical order).Function will be a key secondary in the United States
2. Change from baseline at Day 84 in knee pain as assessed by the average pain subscale score of the WOMAC® NRS 3.1 Index.
3. Change from baseline at Day 84 in function as assessed by the average functional subscale score of the WOMAC® NRS 3.1 Index.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Paradigm Biopharmaceuticals (USA) Inc.

Sponsor organisation

Paradigm Biopharmaceuticals (USA) Inc.

Address

31 West 34th Street

City

New York

Postcode

10001-3009

Country

United States

Scientific contact point

Organisation

Paradigm Biopharmaceuticals (USA) Inc.

Contact name

Director of Clinical Operations

Public contact point

Organisation

Paradigm Biopharmaceuticals (USA) Inc.

Contact name

Director of Clinical Operations

Locations

3 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications