Paradigm Biopharmaceuticals Ltd (ASX:PAR) will make an amendment to its clinical trial protocol for the use of pentosan polysulfate sodium (PPS) to treat knee osteoarthritis (OA) patients following a query from the US Food and Drug Administration (FDA).
Paradigm submitted an Investigational New Drug (IND) application in late March this year for the use of its flagship drug PPS to treat pain in knee OA patients and has been in communications with the regulator in the months since.
The latest request from the FDA regarding adrenal gland function related to a preclinical finding in the adrenal gland of rats only and was not seen in the adrenal gland of dogs; this one preclinical finding has been the focus of the ongoing US FDA review.
Protocol amendment
Paradigm CEO Paul Rennie said Paradigm would amend its clinical trial protocol following a request from the FDA to modify its adrenal screening and mitigation plan.
“We plan to amend our clinical trial protocol, including all the FDA’s requests, and respond to the FDA within the next week; we assume the FDA may again take 30 days to respond,” he said.
“Adrenal gland malfunction has not previously been seen by Paradigm or bene pharmaChem in our ongoing pharmacovigilance. This one preclinical finding has been the focus of the ongoing US FDA review.”
“Although we understand the agency's obligations for thorough reviews which commenced in March of this year, I am confident that the FDA and Paradigm have now attained a pathway to commence our phase 3 clinical trial in the US.”
It is expected to be a minor delay. Late last week, Paradigm received Australian ethics approval for the phase 3 trial.
FDA timeline
March 26, 2021
April 26, 2021
Paradigm flags follow-up questions from the FDA outside the initial 30-day IND review period
May 25, 2021
Paradigm to respond to feedback from the FDA on non-clinical studies and mitigation strategies within 30 days
June 30, 2021
July 30, 2021
The FDA accepts Paradigm responses on five of six questions, seeks further clarification on one remaining matter relating to non-clinical interpretation and clinical mitigation, Paradigm responds with changes to the clinical trial protocol, including a comprehensive adrenal screening protocol and clinical monitoring as part of its mitigation plan, following consultation with external endocrinologists
September 24, 2021
Paradigm receives Australian ethics approval for the phase 3 trial
September 27, 2021
Paradigm to amend its clinical trial protocol including all FDA requests, and respond within the next week.
- Daniel Paproth