Paradigm Completes Phase 3 Enrolment at 538 Patients, Locking in 2026-27 Results
Paradigm Biopharmaceuticals has completed enrolment in its pivotal Phase 3 PARAOA012 trial evaluating Zilosul (injectable pentosan polysulfate sodium) for knee osteoarthritis pain, with 538 participants commencing treatment. This exceeds the original target of 466 participants and represents the company’s largest clinical study using the selected Phase 3 dosing regimen of 2mg/kg administered twice weekly for six weeks.
The overshoot reflects participants already undergoing screening when the enrolment target was reached. Consistent with ethical obligations and standard clinical trial practice, these participants were permitted to complete the screening process and, where eligible, were enrolled into the study. Completion of this milestone removes a significant execution risk from the Phase 3 program and enables the company to focus on treatment completion, patient follow-up and delivery of upcoming clinical milestones.
What knee osteoarthritis is and why new treatments matter
Osteoarthritis is a degenerative joint condition characterised by the breakdown of cartilage, causing pain, stiffness and reduced mobility in affected joints. The condition affects more than 500 million people worldwide, making it one of the largest and fastest-growing causes of disability globally.
Current treatment options remain largely focused on symptom management. Patients typically cycle through analgesics, anti-inflammatory therapies and intra-articular injections before many eventually progress to joint replacement surgery. Notably, there are no approved disease-modifying osteoarthritis therapies currently available.
The need for safe, effective, non-opioid therapies capable of delivering durable improvements in pain and function remains substantial. A successful Phase 3 result positions Zilosul in a large therapeutic gap with limited competition from disease-modifying alternatives, addressing a major global unmet medical need.
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Trial design and what the data will measure
PARAOA012 is a multicentre, randomised, double-blind, placebo-controlled Phase 3 study conducted across 65 clinical sites in Australia, United States, Hong Kong and Moldova. The study’s primary endpoint is the change from baseline in Weekly Average Daily Pain (ADP) score at Day 112.
Key secondary endpoints assess physical function, patient global assessment, responder outcomes and other clinically meaningful measures of treatment benefit. The 538-participant dataset is expected to contribute to a robust clinical dataset while maintaining the study’s planned timelines and statistical analysis framework.
Trial summary:
- Trial type: Phase 3, double-blind, placebo-controlled
- Sites: 65 across 4 countries
- Enrolled: 538 participants
- Primary endpoint: Weekly ADP score change at Day 112
- Dosing regimen: 2mg/kg, twice weekly, six weeks
Interim analysis and top-line results timeline
The Interim Analysis remains on track for September 2026 (Q3 CY2026). Importantly, the Interim Analysis is based on the first 50% of participants reaching the relevant assessment milestone and is independent of the enrolment completion announced today.
Top-line Phase 3 results remain on track for Q1 CY2027. Completion of enrolment ensures the study maintains these planned timelines and enables focus on treatment completion, patient follow-up and delivery of upcoming clinical milestones.
Paradigm’s upsized $14 million placement, completed ahead of the interim analysis, extended the company’s pro forma cash position to approximately $45 million, providing runway through to the end of CY2026 without requiring additional dilutive equity under the current plan.
These two near-term catalysts now locked in — Interim Analysis in September 2026 and top-line results in Q1 2027 — represent the next major valuation inflection points for the company. Investors can now focus on upcoming clinical readouts rather than recruitment execution.
Milestones completed and upcoming catalysts
| Milestone | Status | Timing |
|---|---|---|
| 50% Dosing Milestone | Completed | March 2026 |
| European Expansion (Moldova sites activated) | Completed | — |
| Independent DSMB 20% Safety Review | Completed, no material safety concerns | — |
| Enrolment Complete (538 participants) | Completed | June 2026 |
| Interim Analysis Population Day 112 Assessments | Expected | Q3 CY2026 |
| Independent DSMB Review of Interim Analysis | Expected | Q3 CY2026 |
| Interim Analysis Outcome | Expected | Q3 CY2026 |
| Phase 3 Top-Line Results | Expected | Q1 CY2027 |
Multiple de-risking milestones have already been achieved. The DSMB safety review completion with no material concerns identified provides additional confidence ahead of efficacy readouts.
Executive Chairman outlines significance of milestone
Paul Rennie, Executive Chairman
“Completion of enrolment and commencement of treatment for 538 participants represents a defining milestone for Paradigm and one of the most significant achievements in the Company’s history. Successfully executing a global Phase 3 study across 65 sites and four countries reflects the dedication of our clinical operations team, investigators, study coordinators and, most importantly, the patients who have chosen to participate in this important study.”
Rennie emphasised the therapeutic potential of the treatment, stating: “We believe Zilosul® has the potential to become an important new non-opioid treatment option for patients suffering from knee osteoarthritis and look forward to advancing the program through its next major development milestones.”
The Executive Chairman also highlighted that successful completion of enrolment further de-risks the Phase 3 program and positions Paradigm for a series of significant upcoming milestones, with the company remaining on track for the Interim Analysis expected in September 2026 and top-line Phase 3 results anticipated in Q1 2027.
Prior clinical evidence supporting the Phase 3
Previous clinical studies of Zilosul have demonstrated statistically significant improvements in pain and function. Evidence of favourable effects on key structural and biological markers associated with OA progression has been observed in earlier trials.
Phase 2 cartilage degradation biomarker data presented at the 2026 OARSI Congress showed approximately 50-74% reductions in synovial ARGS versus placebo at Day 56, with those changes correlating directly with clinical improvements in pain and function scores.
PARAOA012 has been designed to confirm these findings in a pivotal Phase 3 setting. The Phase 3 is not a first attempt but builds on earlier clinical signals, which increases confidence in the trial design and endpoint selection. Positive prior data provides support for the dosing regimen and assessment framework being used in the current study.
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Investor webinar scheduled for 18 June 2026
Paradigm will host an investor webinar on Thursday, 18 June 2026 at 11:00am AEST to provide shareholders and investors with an update on the company’s Phase 3 clinical trial program and upcoming milestones.
Investors can submit questions prior to the webinar by emailing investorrelations@paradigmbiopharma.com or through the InvestorHub platform. Questions may also be submitted during the webinar. A recording of the webinar will be made available on the company’s website following the event.
About Paradigm Biopharmaceuticals
Paradigm Biopharmaceuticals is a late-stage drug development company focused on delivering therapies for unmet medical needs. The company’s current focus is developing iPPS for diseases where inflammation plays a major pathogenic role, including osteoarthritis, which is at Phase 3 stage. Paradigm is listed on the ASX under the ticker PAR.
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