Paradigm Biopharmaceuticals Ltd (ASX:PAR), a clinical-stage biopharmaceutical company specialising in the treatment of pain associated with musculoskeletal disorders driven by injury, inflammation, ageing, degenerative disease, infection or genetic predisposition, has randomised and dosed the first subjects in its PARA_OA_002 clinical trial.
The randomised, double-blind and placebo-controlled trial, which is being conducted across the US, Australia, the UK and Europe, will evaluate injectable pentosan polysulfate sodium (injectable PPS), registered as Zilosul®, for the treatment of pain associated with knee osteoarthritis.
Australian trials underway
The Australian Clinical Research Network in NSW enrolled the first subjects in Australia in the last quarter of 2021. There are now eight sites in Australia, and all are on schedule to screen subjects in January.
Of these eight local sites, four are already screening subjects, and the company reports that the first two subjects have now been dosed.
“Dosing the first participants in our PARA_OA_002 Phase 3 clinical program is an important achievement for Paradigm and for the development of Zilosul® to treat the millions of people globally suffering from knee osteoarthritis,” Paradigm chief medical officer and interim CEO Dr Donna Skerrett said.
“We now look forward to ramping up recruitment and enrolment throughout Australia and look forward to updating shareholders on first participant dosing in the US shortly.”
Addressing huge market potential
Osteoarthritis (OA) is the most prevalent form of joint disease, affecting up to 16% of the population in the developed world, with more than 72 million people in the US, Europe, Canada and Australia suffering from it.
The prevalence of OA is increasing in line with an ageing population and increasing rates of obesity. By 2030, the number of people suffering from OA in the US alone is predicted to increase by 86% to 67 million.
Assuming there is a similar increase across the other relevant markets, even allowing for lower rates of obesity in non-US markets, it is plausible that more than 120 million people will be suffering from osteoarthritis by 2030.
Solutions to painful disease
This disease can have a significant impact on daily functioning. There is currently no known cure or spontaneous remission and it is associated with irreversible structural damage and progression over time. There are no drugs approved that can prevent, stop, or even restrain progression of OA.
Paradigm hopes to commercialise a solution for this unmet need.
About the trial
The purpose of PARA_OA_002 is to measure the change in pain and function with subcutaneous injections of PPS compared with subcutaneous injections of placebo in participants with knee osteoarthritis pain. The trial will assess the dose and treatment effect on participants.
Stage 1 involves a Phase 2b dose selection, with randomised participants receiving one of three dose regimens or a placebo for six weeks. Once the team has identified a dose based on an optimal balance of efficacy and safety, participants will be randomly allocated to receive one of four different combinations of the PPS and/or a placebo.
In Stage 2, participants will be randomised 1:1 to receive the selected PPS dose regimen or placebo for six weeks.
The primary endpoint in the pivotal study is a change from baseline at day 56 in pain, with secondary outcomes including change from baseline at multiple time points out to day 168 in pain and function, patient global impression of change, and quality of life.
Lead investigator
The Australian lead investigator for PARA_OA_002 will be A/Prof Andrew Östör, a consultant rheumatologist at Cabrini Medical Centre, principal investigator at Emeritus Research, Melbourne and an Associate Professor in the Department of Medicine at Monash University, who was formerly director of the Rheumatology Clinical Research Unit at Addenbrooke’s Hospital, Cambridge, UK.
His research interests include early inflammatory arthritis, osteoarthritis, biologic and novel treatments for rheumatic diseases, rheumatic manifestations of checkpoint inhibitors and disorders of the shoulder joint.
Prof Östör was the lead investigator for Paradigm’s Phase 2b clinical study.
What’s next?
The company has identified approximately 65 sites throughout the US and AUS, with additional sites being added in Europe and the United Kingdom to accelerate recruitment.
Paradigm expects to report on first participant dosing in the United States during the current quarter.
Dose selection will commence following completion of Day 84 of stage 1 participants, which is expected in the first half of next year.
The company expects to begin filing regulatory applications with the European Medicines Agency and EU member countries for the confirmatory study, PARA_OA_003, soon after confirmation of the selected dose.