HIPGEN: a randomized, multicentre phase III study using intramuscular PLacenta-eXpanded stromal cells therapy for recovery following hip fracture arthroplasty

Abstract

Aims The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells. Methods HIPGEN is a multicentre, multinational, randomized, double-blind, placebo-controlled trial. A total of 240 patients aged 60 to 90 years with low-energy femoral neck fractures (FNF) will be allocated to two arms and receive an intramuscular injection of either 150 × 106 PLX-PAD cells or placebo into the medial gluteal muscle after direct lateral implantation of total or hemi hip arthroplasty. Patients will be followed for two years. The primary endpoint is the Short Physical Performance Battery (SPPB) at week 26. Secondary and exploratory endpoints include morphological parameters (lean body mass), functional parameters (abduction and handgrip strength, symmetry in gait, weightbearing), all-cause mortality rate and patient-reported outcome measures (Lower Limb Measure, EuroQol five-dimension questionnaire). Immunological biomarker and in vitro studies will be performed to analyze the PLX-PAD mechanism of action. A sample size of 240 subjects was calculated providing 88% power for the detection of a 1 SPPB point treatment effect for a two-sided test with an α level of 5%. Conclusion The HIPGEN study assesses the efficacy, safety, and tolerability of intramuscular PLX-PAD administration for the treatment of muscle injury following arthroplasty for hip fracture. It is the first phase III study to investigate the effect of an allogeneic cell therapy on improved mobilization after hip fracture, an aspect which is in sore need of addressing for the improvement in standard of care treatment for patients with FNF. Cite this article: Bone Jt Open 2022;3(4):340–347.

PACE: randomized, controlled, multicentre, multinational, phase III study of PLX-PAD for critical limb ischaemia in patients unsuitable for revascularization: randomized clinical trial

“…In a previous phase I/II study 17 in patients with intermittent claudication using a different PLX-PAD dose, a subpopulation that received two repeated intramuscular injections of a high dose of PLX-PAD cells from two donors into the affected leg showed improved pain-free and maximum walking distance. Moreover, PLX-PAD improved muscle strength in patients after hip arthroplasty associated with immunomodulation in both a phase I/IIa study 18 and a phase III study 19 , 20 .…”

Perinatal derivatives: How to best characterize their multimodal functions in vitro. Part C: Inflammation, angiogenesis, and wound healing

“…Improved techniques for tissue preservation, as well as advances in isolation and culture procedures for PnD cells facilitate the way for early phase clinical trials in diverse indications, such as the application of PLacental-eXpanded (PLX-PAD) stromal cells for the muscle recovery after hip arthroplasty ( Winkler et al, 2022 ), multiple sclerosis ( Lublin et al, 2014 ), pulmonary fibrosis ( Chambers et al, 2014 ), and also COVID-19 ( Hashemian et al, 2021 ; Sadeghi et al, 2021 ).…”