The initial phase of the project included preparation, submission and finalisation of all study documents. Clinical grade PLX-PAD batches were successfully manufactured, stored and used for the patients’ treatment and sent for accompanying in-depth characterisation to the partners. Consequently, the randomized, double-blind, multicentre, placebo-controlled phase III trial for restoring muscle function, mobilisation and reduction of post-operative stress-related immune disbalance in hip fracture patients treated with PLX-PAD cells after arthroplasty has been successfully completed. To meet the negative impact on enrollment and follow-up during the COVID-19 pandemic, home and phone visits were implemented in the study protocols.
In 2021 enrolment has been completed with 240 patients found eligible for randomization into the trial at 21 study sites in Europe, Israel and in the US. After the fulfilment of preparatory tasks analyzing the mechanism of action, samples from study patients are also studied in order to identify surrogate biomarkers for therapy response and to reveal paracrine as well as immune-mediated mechanisms of actions of PLX-PAD on muscle regeneration. These mechanistical side studies help to understand the mode-of-action of the applied therapy. To keep patients engaged during the trial, a HIPGEN-specific ‘Be the Partner’ platform has been created and launched.
Following the completion of the primary efficacy analysis in July 2022, which showed that the trial did not meet the primary endpoint, the Short Physical Performance Battery, a decision was made to terminate the trial early after patient visit week 52. However, a post hoc analysis could show, that PLX-PAD was an effective accelerator of muscle strength and regeneration. A significant increase in Hip Abduction Strength (HAS) from week 6 was observed at week 26 and week 52 for patients treated with PLX-PAD (n=120), both in the injured leg (p=0.047 p=0.0022) and in the uninjured leg (p=0.073 p=0.0046) compared to placebo (n=120). This new data confirms the results on HAS found in the previously performed phase I/II study. The biomarker analysis revealed, among other results based on a broad portfolio of analyses, trends for a faster recovery of cellular immune parameters, such as HLA-DR on monocytes, and modulation of regeneration, such as in the CD4/CD8 ratio. The in vivo mechanism of action analyses demonstrated pro-regenerative and anti-inflammatory effects of PLX-PAD on human myoblasts from donors and HIPGEN patients.
All patients were followed up until week 52 after treatment, and sites have been requested to follow up patients per telephone who already have been at this visit.
In addition to the scientific progress, the overall awareness of Advanced Therapies in hip fracture patients and of the HIPGEN project itself increased due to diverse dissemination activities by all partners, for example via the HIPGEN website, social media, scientific and public presentations/posters at conferences and workshops as well as the video of the public session of the final meeting in Brussels.
