Paradigm Biopharmaceuticals Ltd. announced that the first subject in the United Kingdom (UK) has been randomised and dosed in the pivotal PARA_OA_002 clinical trial, evaluating injectable pentosan polysulfate sodium (iPPS/Zilosul®) for the treatment of pain associated with knee osteoarthritis (OA). The first subject was randomised at Leeds University, by lead investigator, Professor Hemant Pandit. Paradigm aims to activate a total of seven sites across the UK for this phase 3 study.

This PARA_OA_002 global phase 3 trial has activated 8 sites across Australia, and 58 sites in the US. From the start of the calendar year, clinical trial site activation has been a key focus for Paradigm, to enable the largest pool of potential candidates to be identified and processed for participation. Site selection, initiation, and activation for Europe and Canadian is in progress with Paradigm to update investors as milestones are reached.

The purpose of this pivotal phase 3 study is to establish the efficacy of subcutaneous injections of PPS (iPPS) participants with knee OA pain. This is a two-stage, adaptive, randomised, double-blinded, placebo-controlled, multicentre (US/CAN/AUS/UK/EU) study that will evaluate both the dose and treatment effect of iPPS in participants with knee OA pain. Stage 1 will comprise a phase 2b dose selection component, with randomised participants receiving 1 of 3 iPPS dose regimens or placebo for 6 weeks.

The primary objective of stage 1 will be to select the dose for use in stage 2 and in Paradigm's confirmatory trial (PARA_OA_003). The selected dose will be based on an optimal balance of efficacy and safety. In stage 2, participants will be randomised 1:1 to receive the selected PPS dose regimen or placebo for 6 weeks.

The primary endpoints in this pivotal study are changes from baseline at day 56 (two weeks after the final dose) in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain. Secondary outcomes include change from baseline at multiple time points out to day 168 (24 weeks from the start of the study, and 18 weeks after the last treatment) in WOMAC pain and function, Patient Global Impression of Change (PGIC), and Quality of Life (QoL) assessments.