During the first reporting period, Orthox completed the preclinical verification, validation testing of FibroFix™ Cartilage and the associated surgical instrument set, and prepared the majority of documentation required for clinical trial submissions. The preclinical results showed the FibroFix™ implants to be completely biocompatibility under the rigorous ISO10993 requirements; show promising performance in an appropriate animal model of cartilage repair demonstrating implant integration and new cartilage deposition; possess excellent physical properties including mechanical and surface properties that were a close match for human cartilage tissue; and could be implanted using a quick, straightforward and reproducible surgical procedure that resulted in stable implant fixation into the knee joint. The company also made considerable progress on the production scale up, validation and regulatory certification achieving compliance with ISO13485 manufacturing standard and GMP production.
During the second period of the project manufacturing scale up to meet clinical trial requirements was successfully completed, a new company website was launched and, with the removal of Covid-19 restrictions, project results were disseminated more widely through conference presentations as well as project press releases and video productions. A new Company business plan and associated investor materials were developed and used to successfully raise Series A investment finance which was used to support project objectives including progress of FibroFix™ Cartilage into clinical phase (The FFLEX Study).
Clinical trial submissions for the FFLEX clinical study to evaluate FibroFix™ Cartilage in 75 patients were made to the national ethical and regulatory authorities in the UK. The FFLEX clinical investigation (ClinicalTrials.gov Identifier: NCT05560490) pre-market clinical investigation was a multicentre, prospective, non-randomised, open-label, first-in-human clinical investigation using FibroFix™ Cartilage to treat large (up to 5cm2) and potentially osteoarthritic lesions in the smooth, stiff articular cartilage found in joints. The objective of this clinical investigation was to demonstrate the clinical safety and performance of FibroFix™ Cartilage.
In a change to the projects structure, to mitigate the risks presented by the combination of Brexit and the Covid-19 pandemic, clinical trial submissions were also brought forward in continental Europe as well, with an application to run the FFLEX clinical trial in Hungarian sites made to the national ethical and regulatory authorities there too. Approvals from all requisite authorities in both countries were achieved and recruitment of the FFLEX clinical trial was initiated with two patients enrolled onto the Study in late 2022.
FibroFix™ Cartilage P was implanted into 2 patients at the lead site the UK site, Bristol Southmead Hospital, for repair of major cartilage lesions in the medial femoral condyle of the knee joint. Initial clinical signs were positive with encouraging patient recovery and initial pain reduction. Implants were retained in the implantation site with no indication of structural deterioration on MRI. However, persistent swelling in the implanted joints led to implant removal between 3 and 6 months and the trial being halted with root cause analysis undertaken.
