Pluristem conducted a Phase II, randomized, double blind, placebo controlled trial in patients undergoing a total hip replacement (THR) due to osteoarthritis. The aim of the study was to evaluate the safety and efficacy of 2 doses of PLX-PAD for the regeneration of the gluteus medius muscle injured during the THR. Patients were assigned to receive either 150 or 300 million PLX-PAD cells, or placebo. PLX-PAD or placebo were administered directly to the injured muscle during the surgery.
Efficacy data were collected at clinic visits for up to 6 months, while safety data were collected during clinic visits for up to 1 year.
The primary efficacy endpoint was the change in the strength of the gluteus medius muscle 6 months after surgery, and the key secondary endpoint was the change in the muscle volume of the gluteus medius 6 months after surgery, as measured by magnetic resonance imaging (MRI).
The study met both the primary efficacy and key secondary endpoints. Both patient groups treated with PLX-PAD showed efficacy, as measured by a greater increase in the gluteus medius muscle strength than the patients receiving placebo, with the group receiving the 150 million cell dose displaying a statistically significant 500% improvement over the placebo group (p=0.0067). Patients treated with the 300 million cell dose showed a 300% improvement over the placebo (p=0.18).
Graph 1: Mean change in strength of the Gluteus Medius at Week 26 post surgery
MRI of the gluteus medius muscle indicated an increase in volume in those patients treated with PLX-PAD versus the placebo group. Those who received the 150 million cell dose showed a statistically significant improvement in muscle volume of approximately 300% over the placebo group (p=0.004). Patients treated with the 300 million cell dose showed an approximately 150% improvement approximately 150% over placebo (p=0.19).
Graph 2: Mean change in volume of the Gluteus Medius at Week 26 post surgery
Data also showed that, six months after surgery, the magnitude of improvement in the muscle force of the contralateral (non-operated) gluteus medius muscle was approximately 40 times larger in patients treated with 150 million PLX-PAD cells than in those who received placebo, and the difference was statistically significant (p=0.0114). Patients treated with 300 million PLX-PAD cells also showed a larger increase in muscle force than patients injected with placebo (p=0.227). These data on the force of the muscle in the contralateral leg suggest that PLX-PAD cells can exert a systemic as well as a local effect.
Phase III study Hip Fracture
The U.S. Food and Drug Administration (FDA) has cleared Pluristem’s Investigational Drug Application (IND) for a Phase III study of its PLX-PAD cell therapy in the treatment of muscle injury following surgical repair (arthroplasty) of the hip joint due to fracture. Pluristem is in discussions with several EU countries to approve this study in Europe as well and expects to begin patient enrollment in both regions during 2018.
The Phase III Hip Fracture Study (Hipgen study) has been awarded an $8.7 million grant from European Union’s Horizon 2020 program, which is its largest Research and Innovation program. The collaborative project includes leading European research institutes and clinical sites, which undertake an extensive scientific program in parallel to the trial, using in-depth immunological, endocrine, and molecular analyses to better understand the mechanism of action of PLX-PAD in hip fracture.
PLX-PAD program in hip fracture might also be eligible for the EMA’s Adaptive Pathways pilot project which may allow for early marketing approval in Europe, as well as the Breakthrough Therapy designation and benefit from the 21st Century Cures Act.
Femoral neck fracture is the most common form of hip fracture with annual treatment costs in the U.S. estimated to be between $10 to $15 billion, and are expected to rise due to the aging population, with mortality rates of up to 36%.
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