Paradigm Biopharmaceuticals Initiates a Phase 3 Clinical Trial in Knee Osteoarthritis Across the U.S

The company plans an estimated 56 clinical trial locations nationwide

MELBOURNE, Australia, March 17, 2022 /PRNewswire/ -- Paradigm Biopharmaceuticals (ASX: PAR) a global biopharmaceutical company driven to improve patients' lives through repurposing existing drugs and pioneering new solutions for unmet medical needs, is announcing today the official launch of their U.S. clinical trial program with an estimated 56 planned clinical trial locations nationwide for the conduct of the pivotal phase 3 trial to support registration of Pentosan Polysulfate Sodium (PPS) for osteoarthritis (OA) of the knee.  

Established in 2014, Paradigm Biopharmaceuticals has successfully identified, repurposed, and patented PPS, for the management of pain and inflammation, associated with musculoskeletal disorders including osteoarthritis (under the trademark Zilosul®) and the rare disease mucopolysaccharidosis.  

Paradigm is expanding its US operations to support the registration studies for the OA program. Simultaneously Paradigm is announcing activation of the phase 3 clinical trial network for Zilosul® to treat knee osteoarthritis. This is significant as osteoarthritis is the most common cause of disability among adults and affects more than 72 million people across the U.S., Canada, EU-5, and Australia.^1,2 

The purpose of this study is to measure the change in pain and function with subcutaneous injections of PPS compared with subcutaneous injections of placebo in participants with kOA pain. This is a 2-stage, adaptive, randomised, double-blind, placebo-controlled, multicenter (US/AUS/UK/EU) study that will evaluate the dose and treatment effect of PPS in participants with kOA pain.

Stage 1 comprises a phase 2b dose selection, with participants randomised receiving 1 of 3 PPS dose regimens or placebo for 6 weeks. The primary objective of stage 1 is to select the dose for use in stage 2, the selected dose will be based on an optimal balance of efficacy and safety.

Participants in stage 1 will be randomly allocated to receive:

• 1.5 mg/kg calculated for ideal body weight (IBW) PPS twice weekly
• 2 mg/kg IBW PPS once weekly + placebo once weekly
• Fixed dose (100/150mg/180mg PPS ≤65/≥65 to ≤90/>90 kg IBW) once weekly + placebo once weekly
• Placebo twice weekly

In stage 2, participants will be randomised 1:1 to receive the selected PPS dose regimen or placebo for 6 weeks.

The primary endpoint in the pivotal study is a change from baseline at Day 56 in WOMAC® pain with secondary outcomes including change from baseline at multiple time points out to day 168 in WOMAC® Pain and Function, Patient Global Impression of Change and Quality of Life.

"The activation of the phase 3 in knee OA clinical trial in the U.S. represents a significant step in Paradigm's growth as a global leader in repurposing existing drugs." Says Interim CEO, Dr. Donna Skerrett. "There is encouraging data indicating that PPS is not only an effective treatment in navigating pain management, but also for diseasing modifying potential, a significant medical breakthrough which does not exist for the treatment for osteoarthritis." 

Adopting an intelligent and agile approach to clinical R&D, Paradigm's experienced team has built and sustained strong and successful collaborations with leading clinical researchers in the field. By repurposing FDA approved drugs, Paradigm aims to shorten the drug development cycle time for chosen applications and minimize development costs. Paradigm is working in concert with, and has exclusive supply agreements with, the proprietary and only FDA approved manufacturer of PPS, bene pharmaChem.³ 

Director of Investor Relations, Simon White, highlighted that this "approach to market helps Paradigm scale costs in drug development and apply additional focus and resources on globally harmonizing the drug application, and clinical program which aims to cumulatively expedite Zilosul's introduction to the U.S. and other global markets." 

About Paradigm Biopharmaceuticals: Paradigm Biopharmaceuticals (ASX: PAR) is a global biopharmaceutical company driven to improve patients' lives through repurposing existing drugs and pioneering new solutions for unmet medical needs.  The company aims to identify and leverage new applications for drugs in late-stage development.   

Since their founding in 2014, Paradigm has successfully identified, repurposed, and patented Pentosan Polysulfate Sodium (PPS), for the management of pain and inflammation, associated with musculoskeletal disorders including osteoarthritis (under the trademark Zilosul®) and the rare disease mucopolysaccharidosis. Paradigm's approach to market is driven by core competencies with experienced management at both board and executive levels and in clinical and commercial pharmaceutical development.   

For more information about Paradigm Biopharmaceuticals please visit  https://paradigmbiopharma.com/    

About WOMAC® Scores: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC®) is a widely used, proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain, stiffness, and physical functioning of the joints. It consists of 24 items divided into 3 subscales [8]:

• Pain (5 items): during walking, using stairs, in bed, sitting or lying, and standing upright.
• Stiffness (2 items): after first waking and later in the day.
• Physical Function (17 items): using stairs, rising from sitting, standing, bending, walking, getting in / out of a car, shopping, putting on / taking off socks, rising from bed, lying in bed, getting in / out of bath, sitting, getting on / off toilet, heavy domestic duties, light domestic duties
  https://www.womac.com/womac/index.php

1. Arthritis by the Numbers - Book of Trusted Facts & Figures 2020. https://www.arthritis.org/getmedia/73a9f02d-7f91-4084-91c3-0ed0b11c5814/ABTN-2020-FINAL.pdf
2. Long H, Liu Q, Yin H, et al. Prevalence trends of site-specific osteoarthritis from 1990 to 2019: findings from the Global Burden of Disease Study 2019. Arthritis Rheumatol. 2022;n/a(n/a). doi:10.1002/art.42089
3. Paradigm Biopharmaceuticals announcement Sep 2020. Paradigm Extends Term, Indications and Territories Under Exclusive Supply Agreement with Bene Pharmachem.

SOURCE Paradigm Biopharmaceuticals