Paradigm Biopharmaceuticals Ltd (ASX: PAR) has submitted its Investigational New Drug (IND) application to the US Food and Drug Administration (FDA) for the planned Pivotal study and Extension study with PPS (Zilosul) for the treatment of patients with Knee Osteoarthritis (OA).
Paradigm CMO, Dr Donna Skerrett, said the submission of the IND application marks a significant milestone for the company as Paradigm is now focused on the Pivotal stage of clinical development of Zilosul and is the culmination of several informative meetings with global regulators throughout 2020.
In preparation for the IND submission and commencement of the pivotal clinical programme, Paradigm’s goal was to conduct multiple meetings with key regulatory bodies to ensure the clinical trial design would be acceptable on a global platform and meet all obligations required for registration upon successful trial results.
Paradigm attended a Pre-IND meeting in February 2020 where the company met with the FDA to discuss the clinical trial protocol and received feedback from a Type-C meeting2 in December 2020, where the written response to questions posed by Paradigm was received from the US FDA on the proposed clinical trial design.
Regulatory engagement with the EMA was also achieved via a virtual Scientific Advice meeting in September 2020. This was another major milestone toward the goal of a global harmonised clinical program with feedback from the EMA supporting Paradigm’s clinical development to date and registration plans for Zilosul in Europe. Based on the feedback, applications to commence clinical trials in EU member countries may begin, with a clear path to product registration.
The key items identified by the EMA and FDA throughout the feedback process that have been addressed prior to the IND application submission were:
- The minimally effective dose to be established.
- The requirement for a second phase 3 confirmatory study.
- Additional Pre-clinical studies to be completed at GLP standard.
- Increased number of patients to satisfy safety requirements for a new dosage form.
- WOMAC Pain and WOMAC Function to be key endpoints.
The IND application is an over 30,000-page submission which includes reports on the phase 1 study in healthy volunteers that was completed in Q4 2020 as well as several non-clinical studies that detail the pharmacokinetics and toxicology of PPS. The submission also describes the GMP manufacture of the active substance and the drug product used for the pivotal phase 3 studies.
Once the IND is ‘open’, Paradigm may begin recruitment and screening of participants for the pivotal Para_002 clinical study upon institutional ethics committee approval(s). Site selection is close to being finalised in the US and Australia with 60 of a planned 65 sites already approved to participate in the clinical trial. Paradigm remains on track to have the first subject begin screening in Q2 CY2021.
This IND submission is the product of several informative meetings with the US FDA and EMA where Paradigm’s clinical and regulatory teams received critical feedback on the requirements of the data package for submission and overall clinical trial design to ensure it would meet the regulators needs for registration,” Dr Skerrett said.
“This led to adjustments in the OA clinical program to make sure Paradigm would have all necessary data to not only open the IND but also to have a harmonised global clinical trial design.
“We believe the process of gaining this important feedback from multiple regulators has de-risked our overall clinical programme giving us confidence that should our Pivotal and Confirmatory studies be successful, the company will have all necessary data required for registration of Zilosul at a minimum with the FDA, EMA and TGA.”
Osteoarthritis (OA) is the most common joint disorder in the United States. Symptomatic knee OA occurs in 10% men and 13% in women aged 60 years or older. The number of people affected with symptomatic OA is likely to increase due to the aging of the population and the obesity epidemic.
Current estimates indicate that there are 14 million US adults with symptomatic knee osteoarthritis. The overall number of US adults affected by OA in any joint has increased during recent decades and is estimated to affect over 30 million US adults today, primarily due to an aging population and an ever- increasing prevalence of obesity.
