Paradigm Biopharmaceuticals Ltd (ASX:PAR) has reported a 45% mean reduction in WOMAC pain subscale score across 34 patients with knee osteoarthritis (OA) using its phase 3 clinical trial product Zilosul.
WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) is a proprietary set of standardised questionnaires used by health professionals to evaluate the condition of patients with OA of the knee and hip, including pain, stiffness, and physical functioning of the joints.
Doctors started treating OA patients with Paradigm’s injectable pentosan polysulfate (iPPS) (Zilosul) from quarter three CY2019 under the Therapeutic Goods Administration Special Access Scheme (TGA SAS).
New data shows that pain reductions in 34 SAS patients being treated using Zilosul are consistent with prior reports under TGA SAS.
WOMAC pain reduction
Paradigm chief executive officer Paul Rennie said: “We are very pleased to see continued real world evidence that Zilosul® reduced Knee OA pain and that the WOMAC pain subscale score showed a reduction of 45%.
“This reduction in pain from baseline compares with the published WOMAC pain reduction of the opioid analgesic, Tramadol.
“Of important relevance to us is that when compared to other treatment options available for OA, Zilosul® has a longer lasting effect”.
“In clinical trials the Patient global impression of Change (PGIC) scale is used as the "gold standard" of clinically significant change and therefore we were delighted to note that 85.7% of SAS patients had shown moderately to definite and considerable improvement in their OA condition with iPPS (Zilosul®) treatment”.
Rennie added: “The number of patients seeking Zilosul® treatment via the TGA SAS is a strong feedback that there is a lack of effective and satisfactory treatment options available for the treatment of OA pain.
“The very well-defined SAS data at 95% confidence intervals is very impressive.
“This means these data have tight standard deviation around the mean with no overlap of intervals between the baseline results and the post PPS treatment results which is very encouraging given the small sample size (n=34).
“This gives us great confidence going forward towards a Phase 3 clinical program”
“The acquisition of real-world evidence concurrent to our FDA IND submission for the Phase 3 OA trial with our newly manufactured Phase 3 trial product provides important ongoing efficacy and safety data.”
Phase 3 clinical trial
Paradigm confirmed that its pre-IND (investigational new drug) meeting with FDA regarding the phase 3 OA trial was both positive and informative.
Key outcomes of the FDA meeting include:
- Primary and secondary endpoints are the same as previous phase 2 trial (pain and function, mean change from baseline)
- Primary endpoint will be mean change in pain using WOMAC questionnaire
- Because Paradigm is proposing a new indication for pentosan polysulfate (treatment of pain in OA), bridging to literature will not serve as one of the two required efficacy studies, therefore the agency requires two adequate and well controlled studies.
- ~750 patients in 1st phase 3 randomized controlled trial (22-month duration)
- ~400 patients in 2nd phase 3 randomized controlled trial (12-month duration but can be run concurrently, with centres in Europe)
Paradigm is expecting a January 2021 start to its phase 3 clinical trial, with readouts anticipated in third quarter CY 2022.